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Sample records for afferent arteriole aa

  1. Superoxide modulates myogenic contractions of mouse afferent arterioles.

    PubMed

    Lai, En Yin; Wellstein, Anton; Welch, William J; Wilcox, Christopher S

    2011-10-01

    Reactive oxygen species enhance or impair autoregulation. Because superoxide is a vasoconstrictor, we tested the hypothesis that stretch generates superoxide that mediates myogenic responses. Increasing perfusion pressure of mouse isolated perfused renal afferent arterioles from 40 to 80 mm Hg reduced their diameter by 13.3±1.8% (P<0.001) and increased reactive oxygen species (ethidium: dihydroethidium fluorescence) by 9.8±2.3% (P<0.05). Stretch-induced fluorescence was reduced significantly (P<0.05) by incubation with Tempol (3.7±0.8%), pegylated superoxide dismutase (3.2±1.0%), or apocynin (3.5±0.9%) but not by pegylated catalase, L-nitroarginine methylester, or Ca(2+)-free medium, relating it to Ca(2+)-independent vascular superoxide. Compared with vehicle, basal tone and myogenic contractions were reduced significantly (P<0.05) by pegylated superoxide dismutase (5.4±0.8), Tempol (4.1±1.0%), apocynin (1.0±1.3%), and diphenyleneiodinium (3.9±0.9%) but not by pegylated catalase (10.1±1.6%). L-Nitroarginine methylester enhanced basal tone, but neither it (15.8±3.3%) nor endothelial NO synthase knockout (10.2±1.8%) significantly changed myogenic contractions. Tempol had no further effect after superoxide dismutase but remained effective after catalase. H(2)O(2) >50 μmol/L caused contractions but at 25 μmol/L inhibited myogenic responses (7.4±0.8%; P<0.01). In conclusion, increasing the pressure within afferent arterioles led to Ca(2+)-independent increased vascular superoxide production from nicotinamide adenine dinucleotide phosphate oxidase, which enhanced myogenic contractions largely independent of NO, whereas H(2)O(2) impaired pressure-induced contractions but was not implicated in the normal myogenic response.

  2. Influence of Connexin40 on the renal myogenic response in murine afferent arterioles

    PubMed Central

    Jacobsen, Jens Christian B; Sorensen, Charlotte M

    2015-01-01

    Renal autoregulation consists of two main mechanisms; the myogenic response and the tubuloglomerular feedback mechanism (TGF). Increases in renal perfusion pressure activate both mechanisms causing a reduction in diameter of the afferent arteriole (AA) resulting in stabilization of the glomerular pressure. It has previously been shown that connexin-40 (Cx40) is essential in the renal autoregulation and mediates the TGF mechanism. The aim of this study was to characterize the myogenic properties of the AA in wild-type and connexin-40 knockout (Cx40KO) mice using both in situ diameter measurements and modeling. We hypothesized that absence of Cx40 would not per se affect myogenic properties as Cx40 is expressed primarily in the endothelium and as the myogenic response is known to be present also in isolated, endothelium-denuded vessels. Methods used were the isolated perfused juxtamedullary nephron preparation to allow diameter measurements of the AA. A simple mathematical model of the myogenic response based on experimental parameters was implemented. Our findings show that the myogenic response is completely preserved in the AA of the Cx40KO and if anything, the stress sensitivity of the smooth muscle cell in the vascular wall is increased rather than reduced as compared to the WT. These findings are compatible with the view of the myogenic response being primarily a local response to the local transmural pressure. PMID:26009638

  3. Autoregulation and conduction of vasomotor responses in a mathematical model of the rat afferent arteriole.

    PubMed

    Sgouralis, Ioannis; Layton, Anita T

    2012-07-15

    We have formulated a mathematical model for the rat afferent arteriole (AA). Our model consists of a series of arteriolar smooth muscle cells and endothelial cells, each of which represents ion transport, cell membrane potential, and gap junction coupling. Cellular contraction and wall mechanics are also represented for the smooth muscle cells. Blood flow through the AA lumen is described by Poiseuille flow. The AA model's representation of the myogenic response is based on the hypothesis that changes in hydrostatic pressure induce changes in the activity of nonselective cation channels. The resulting changes in membrane potential then affect calcium influx through changes in the activity of the voltage-gated calcium channels, so that vessel diameter decreases with increasing pressure values. With this configuration, the model AA maintains roughly stable renal blood flow within a physiologic range of blood flow pressure. Model simulation of vasoconstriction initiated from local stimulation also agrees well with findings in the experimental literature, notably those of Steinhausen et al. (Steinhausen M, Endlich K, Nobiling R, Rarekh N, Schütt F. J Physiol 505: 493-501, 1997), which indicated that conduction of vasoconstrictive response decays more rapidly in the upstream flow direction than downstream. The model can be incorporated into models of integrated renal hemodynamic regulation.

  4. Superoxide enhances Ca2+ entry through L-type channels in the renal afferent arteriole.

    PubMed

    Vogel, Paul A; Yang, Xi; Moss, Nicholas G; Arendshorst, William J

    2015-08-01

    Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in the renal microcirculation is poorly understood. The present experiments examined the acute effect of superoxide generated by paraquat on calcium entry pathways in isolated rat afferent arterioles. The peak increase in cytosolic calcium concentration caused by KCl (40 mmol/L) was 99±14 nmol/L. The response to this membrane depolarization was mediated exclusively by L-type channels because it was abolished by nifedipine but was unaffected by the T-type channel blocker mibefradil. Paraquat increased superoxide production (dihydroethidium fluorescence), tripled the peak response to KCl to 314±68 nmol/L (P<0.001) and doubled the plateau response. These effects were abolished by tempol and nitroblue tetrazolium, but not by catalase, confirming actions of superoxide and not of hydrogen peroxide. Unaffected by paraquat and superoxide was calcium entry through store-operated calcium channels activated by thapsigargin-induced calcium depletion of sarcoplasmic reticular stores. Also unresponsive to paraquat was ryanodine receptor-mediated calcium-induced calcium release from the sarcoplasmic reticulum. Our results provide new evidence that superoxide enhances calcium entry through L-type channels activated by membrane depolarization in rat cortical afferent arterioles, without affecting calcium entry through store-operated entry or ryanodine receptor-mediated calcium mobilization.

  5. Predicted effects of nitric oxide and superoxide on the vasoactivity of the afferent arteriole.

    PubMed

    Layton, Anita T; Edwards, Aurélie

    2015-10-15

    We expanded a published mathematical model of an afferent arteriole smooth muscle cell in rat kidney (Edwards A, Layton, AT. Am J Physiol Renal Physiol 306: F34-F48, 2014) to understand how nitric oxide (NO) and superoxide (O(2)(-)) modulate the arteriolar diameter and its myogenic response. The present model includes the kinetics of NO and O(2)(-) formation, diffusion, and reaction. Also included are the effects of NO and its second messenger cGMP on cellular Ca²⁺ uptake and efflux, Ca²⁺-activated K⁺ currents, and myosin light chain phosphatase activity. The model considers as well pressure-induced increases in O(2)(-) production, O(2)(-)-mediated regulation of L-type Ca²⁺ channel conductance, and increased O(2)(-) production in spontaneous hypertensive rats (SHR). Our results indicate that elevated O(2)(-) production in SHR is sufficient to account for observed differences between normotensive and hypertensive rats in the response of the afferent arteriole to NO synthase inhibition, Tempol, and angiotensin II at baseline perfusion pressures. In vitro, whether the myogenic response is stronger in SHR remains uncertain. Our model predicts that if mechanosensitive cation channels are not modulated by O(2)(-), then fractional changes in diameter induced by pressure elevations should be smaller in SHR than in normotensive rats. Our results also suggest that most NO diffuses out of the smooth muscle cell without being consumed, whereas most O(2)(-) is scavenged, by NO and superoxide dismutase. Moreover, the predicted effects of superoxide on arteriolar constriction are not predominantly due to its scavenging of NO.

  6. Calcium dynamics underlying the myogenic response of the renal afferent arteriole

    PubMed Central

    Edwards, Aurélie

    2013-01-01

    The renal afferent arteriole reacts to an elevation in blood pressure with an increase in muscle tone and a decrease in luminal diameter. This effect, known as the myogenic response, is believed to stabilize glomerular filtration and to protect the glomerulus from systolic blood pressure increases, especially in hypertension. To study the mechanisms underlying the myogenic response, we developed a mathematical model of intracellular Ca2+ signaling in an afferent arteriole smooth muscle cell. The model represents detailed transmembrane ionic transport, intracellular Ca2+ dynamics, the kinetics of myosin light chain phosphorylation, and the mechanical behavior of the cell. It assumes that the myogenic response is initiated by pressure-induced changes in the activity of nonselective cation channels. Our model predicts spontaneous vasomotion at physiological luminal pressures and KCl- and diltiazem-induced diameter changes comparable to experimental findings. The time-periodic oscillations stem from the dynamic exchange of Ca2+ between the cytosol and the sarcoplasmic reticulum, coupled to the stimulation of Ca2+-activated potassium (KCa) and chloride (ClCa) channels, and the modulation of voltage-activated L-type channels; blocking sarco/endoplasmic reticulum Ca2+ pumps, ryanodine receptors (RyR), KCa, ClCa, or L-type channels abolishes these oscillations. Our results indicate that the profile of the myogenic response is also strongly dependent on the conductance of ClCa and L-type channels, as well as the activity of plasmalemmal Ca2+ pumps. Furthermore, inhibition of KCa is not necessary to induce myogenic contraction. Lastly, our model suggests that the kinetic behavior of L-type channels results in myogenic kinetics that are substantially faster during constriction than during dilation, consistent with in vitro observations (Loutzenhiser R, Bidani A, Chilton L. Circ. Res. 90: 1316–1324, 2002). PMID:24173354

  7. Flow modulates myogenic responses in isolated microperfused rabbit afferent arterioles via endothelium-derived nitric oxide.

    PubMed Central

    Juncos, L A; Garvin, J; Carretero, O A; Ito, S

    1995-01-01

    Flow may be a physiological stimulus of the endothelial release of nitric oxide (NO) and prostaglandins (PGs). We tested the hypothesis that pressure-induced constriction of the glomerular afferent arteriole (Af-Art) is modulated by luminal flow via endothelial production of NO. We microdissected the terminal segment of an interlobular artery together with two Af-Arts, their glomeruli (GL) and efferent arterioles (Ef-Art). The two Af-Arts were perfused simultaneously from the interlobular artery, while one Ef-Art was occluded. Since the arteriolar perfusate contained 5% albumin, oncotic pressure built up in the glomerulus with the occluded Ef-Art and opposed the force of filtration, resulting in little or no flow through the corresponding Af-Art. Thus this preparation allowed us to observe free-flow and no-flow Af-Arts simultaneously during stepwise 30-mmHg increases in intraluminal pressure (from 30 to 120 mmHg). Pressure-induced constriction was weaker in free-flow than no-flow Af-Arts, with the luminal diameter decreasing by 11.1 +/- 1.7 and 25.6 +/- 2.3% (n = 30), respectively, at 120 mmHg. To examine whether flow modulates myogenic constriction through endothelium-derived NO and/or PGs, we examined pressure-induced constriction before and after (a) disruption of the endothelium, (b) inhibition of NO synthesis with NW-nitro-L-arginine methyl ester (L-NAME), or (c) inhibition of cyclooxygenase with indomethacin. Both endothelial disruption and L-NAME augmented pressure-induced constriction in free-flow but not no-flow Af-Arts, abolishing the differences between the two. However, indomethacin had no effect in either free-flow or no-flow Af-Arts. These results suggest that intraluminal flow attenuates pressure-induced constriction in Af-Arts via endothelium-derived NO. Thus flow-stimulated NO release may be important in the fine control of glomerular hemodynamics. Images PMID:7769114

  8. [A case of systemic lupus erythematosus associated with severe fibrinoid necrosis located mainly in the glomerular afferent arteriole].

    PubMed

    Morioka, S; Makino, H; Wada, J; Shikata, K; Yamasaki, Y; Ogura, T; Amano, T; Asaumi, A; Okada, S; Ota, Z

    1995-01-01

    We report here, a patient of systemic lupus erythematosus (SLE) with severe fibrinoid necrosis in the afferent arteriole of the glomerulus, in whom antiphospholipid antibody might have contributed to the pathogenesis. A 24-year-old female who was suffering from severe anemia with fragmented red blood cells, acute renal failure and thrombocytopenia, was admitted to our hospital. Further examinations revealed findings compatible with active lupus nephritis. Moreover, she was found to be positive for antiphospholipid antibody, and anticardiolipin antibody, as well as for lupus anticoagulant and syphilis test. Intensive treatment by methylprednisolone pulse therapy, hemodialysis, and double filtration plasmapheresis were performed. However, 13 days after admission she died suddenly because of intracranial hemorrhage. Pathological investigation of renal tissue revealed severe fibrinoid necrosis of the arterioles mainly in the glomerular afferent arteriole associated with diffuse proliferative lupus nephritis. In this case, hemolytic uremic syndrome (HUS) was associated with SLE. Antiphospholipid antibody was considered to be not only an accelerator in the arterial lesions of HUS, but also an initiator of HUS itself.

  9. Interaction of angiotensin II and nitric oxide in isolated perfused afferent arterioles of mice.

    PubMed

    Patzak, A; Mrowka, R; Storch, E; Hocher, B; Persson, P B

    2001-06-01

    The present study was performed to evaluate angiotensin II (Ang II)-nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mice that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed for the NO precursor L-arginine (n = 4), NO inhibitor NG-nitro-L-arginine methyl ester (L-NAME, n = 5), L-NAME after pretreatment with L-arginine (n = 5), Ang II (n = 8), and Ang II after pretreatment with L-NAME (n = 7). Acute administration of L-arginine and L-NAME (both in doses from 10(-6) to 10(-3) mol/L) did not change arteriolar diameter. Moreover, pretreatment with L-arginine did not change the response to L-NAME. However, Ang II, applied in doses of 10(-12), 10(-10), 10(-8), and 10(-6) mol/L, significantly reduced the lumen to 66.5 +/- 7.0% and 62.2 +/- 8.0% at 10(-8) and 10(-6) mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 +/- 13.6% and 25.5 +/- 10.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). In eNOS (-/-) mice (n = 8), the response to Ang II also was enhanced (9.1 +/- 6.0% and 11.2 +/- 8.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). Female mice did not differ from male mice in their reactivity to Ang II (n = 9) and Ang II + L-NAME pretreatment (n = 11). The study shows that (1) it is feasible to microperfuse mouse Af, (2) the basal production of endothelial NO is very low and not inducible by L-arginine in Af of mice, and (3) a counteracting effect of NO is initiated by Ang II. High Ang II sensitivity in eNOS (-/-) mice underscores the considerable role of endothelial-derived NO to balance Ang II vasoconstriction in Af.

  10. Redundant signaling mechanisms contribute to the vasodilatory response of the afferent arteriole to proteinase-activated receptor-2.

    PubMed

    Wang, Xuemei; Hollenberg, Morley D; Loutzenhiser, Rodger

    2005-01-01

    We previously demonstrated that stimulation of proteinase-activated receptor-2 (PAR-2) by SLIGRL-NH(2) elicits afferent arteriolar vasodilation, in part, by elaborating nitric oxide (NO), suggesting an endothelium-dependent mechanism (Trottier G, Hollenberg M, Wang X, Gui Y, Loutzenhiser K, and Loutzenhiser R. Am J Physiol Renal Physiol 282: F891-F897, 2002). In the present study, we characterized the NO-independent component of this response, using the in vitro perfused hydronephrotic rat kidney. SLIGRL-NH(2) (10 mumol/l) dilated afferent arterioles preconstricted with ANG II, and the initial transient component of this response was resistant to NO synthase (NOS) and cyclooxygenase inhibition. This NO-independent response was not prevented by treatment with 10 nmol/l charybdotoxin and 1 mumol/l apamin, a manipulation that prevents the endothelium-derived hyperpolarizing factor (EDHF)-like response of the afferent arteriole to acetylcholine, nor was it blocked by the addition of 1 mmol/l tetraethylammonium (TEA) or 50 mumol/l 17-octadecynoic acid, treatments that block the EDHF-like response to bradykinin. To determine whether the PAR-2 response additionally involves the electrogenic Na(+)-K(+)-ATPase, responses were evaluated in the presence of 3 mmol/l ouabain. In this setting, SLIGRL-NH(2) induced a biphasic dilation in control and a transient response after NOS inhibition. The latter was not prevented by charybdotoxin plus apamin or by TEA alone but was abolished by combined treatment with charybdotoxin, apamin, and TEA. This treatment did not prevent the NO-dependent dilation evoked in the absence of NOS inhibition. Our findings indicate a remarkable redundancy in the signaling cascade mediating PAR-2 -induced afferent arteriolar vasodilation, suggesting an importance in settings such as inflamation or ischemia, in which vascular mechanisms might be impaired and the PAR system is thought to be activated.

  11. Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

    PubMed

    Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

    2015-04-15

    Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

  12. Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange.

    PubMed

    Fellner, Susan K; Arendshorst, William J

    2008-01-01

    In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)) and initiation of vascular contraction are increasingly being delineated. We have recently studied angiotensin II (ANG II)-mediated effects on sarcoplasmic reticulum (SR) mobilization of Ca(2+) and the role of superoxide and cyclic adenosine diphosphoribose in these processes. In the current study we investigated the participation of transient receptor potential canonical channels (TRPC) and a Na(+)/Ca(2+) exchanger (NCX) in Ca(2+) entry mechanisms. Afferent arterioles, isolated with the magnetized polystyrene bead method, were loaded with fura-2 to measure [Ca(2+)](i) ratiometrically. We observed that the Ca(2+)-dependent chloride channel blocker niflumic acid (10 and 50 microM) affects neither the peak nor plateau [Ca(2+)](i) response to ANG II. Arterioles were pretreated with ryanodine (100 microM) and TMB-8 to block SR mobilization via the ryanodine receptor and inositol trisphosphate receptor, respectively. The peak [Ca(2+)](i) response to ANG II was reduced by 40%. Addition of 2-aminoethoxydiphenyl borane to block TRPC-mediated Ca(2+) entry inhibited the peak [Ca(2+)](i) ANG II response by 80% and the plateau by 74%. Flufenamic acid (FFA; 50 microM), which stimulates TRPC6, caused a sustained increase of [Ca(2+)](i) of 146 nM. This response was unaffected by diltiazem or nifedipine. KB-R7943 (at the low concentration of 10 microM) inhibits reverse (but not forward) mode NCX. KB-R7943 decreased the peak [Ca(2+)](i) response to ANG II by 48% and to FFA by 38%. We conclude that TRPC6 and reverse-mode NCX may be important Ca(2+) entry pathways in afferent arterioles.

  13. Remodeling of Afferent Arterioles From Mice With Oxidative Stress Does Not Account for Increased Contractility but Does Limit Excessive Wall Stress.

    PubMed

    Li, Lingli; Feng, Di; Luo, Zaiming; Welch, William J; Wilcox, Christopher S; Lai, En Yin

    2015-09-01

    Because superoxide dismutase (SOD) knockout enhances arteriolar remodeling and contractility, we hypothesized that remodeling enhances contractility. In the isolated and perfused renal afferent arterioles from SOD wild type (+/+) and gene-deleted mice, contractility was assessed from reductions in luminal diameter with perfusion pressure from 40 to 80 mm Hg (myogenic responses) or angiotensin II (10(-6) mol/L), remodeling from media:lumen area ratio, superoxide (O2 (·-)) and hydrogen peroxide (H2O2) from fluorescence microscopy, and wall stress from wall tension/wall thickness. Compared with +/+ strains, arterioles from SOD1-/-, SOD2+/-, and SOD3-/- mice developed significantly (P<0.05) more O2 (·-) with perfusion pressure and angiotensin II and significantly increased myogenic responses (SOD1-/-: -20.7±2.2% versus -12.7±1.6%; SOD2+/-: -7.4±1.3% versus -12.6±1.4%; and SOD3-/-: -9.1±1.9% versus -15.8±2.2%) and angiotensin II contractions and ≈2-fold increased media:lumen ratios. Media:lumen ratios correlated with myogenic responses (r(2) =0.23; P<0.01), angiotensin II contractions (r(2)=0.57; P<0.0001), and active wall tension (r(2) =0.19; P<0.01), but not with active wall stress (r(2)=0.08; NS). Differences in myogenic responses among SOD3 mice were abolished by bath addition of SOD and were increased 3 days after inducing SOD3 knockout (-26.9±1.7% versus -20.1±0.7%; P<0.05), despite unchanged media:lumen ratios (2.01±0.09 versus 2.02±0.03; NS). We conclude that cytosolic, mitochondrial, or extracellular O2 (·-) enhance afferent arteriolar contractility and remodeling. Although remodeling does not enhance contractility, it does prevent the potentially damaging effects of increased wall stress.

  14. Mechanical Buckling of Arterioles in Collateral Development

    PubMed Central

    Liu, Qin; Han, Hai-Chao

    2012-01-01

    Collateral arterioles enlarge in both diameter and length, and develop corkscrew-like tortuous patterns during remodeling. Recent studies showed that artery buckling could lead to tortuosity. The objective of this study was to determine arteriole critical buckling pressure and buckling pattern during arteriole remodeling. Arterioles were modeled as elastic cylindrical vessels with an elastic matrix support and underwent axial and radial growth. Our results demonstrated that arteriole critical buckling pressure decreased with increasing axial growth ratio and radius growth ratio, but increased with increasing wall thickness. Arteriole buckling mode number increased (wave length decreased) with increasing axial growth ratio, but decreased with increasing radius growth ratio and wall thickness. Our study suggests that axial growth in arterioles makes them prone to buckling and that buckling leads to tortuous collaterals. These results shed light on the mechanism of collateral arteriole tortuosity. PMID:23034307

  15. Mechanical buckling of arterioles in collateral development.

    PubMed

    Liu, Qin; Han, Hai-Chao

    2013-01-07

    Collateral arterioles enlarge in both diameter and length, and develop corkscrew-like tortuous patterns during remodeling. Recent studies showed that artery buckling could lead to tortuosity. The objective of this study was to determine arteriole critical buckling pressure and buckling pattern during arteriole remodeling. Arterioles were modeled as elastic cylindrical vessels with an elastic matrix support and underwent axial and radial growth. Our results demonstrated that arteriole critical buckling pressure decreased with increasing axial growth ratio and radius growth ratio, but increased with increasing wall thickness. Arteriole buckling mode number increased (wavelength decreased) with increasing axial growth ratio, but decreased with increasing radius growth ratio and wall thickness. Our study suggests that axial growth in arterioles makes them prone to buckling and that buckling leads to tortuous collaterals. These results shed light on the mechanism of collateral arteriole tortuosity.

  16. Development of the renal arterioles.

    PubMed

    Sequeira Lopez, Maria Luisa S; Gomez, R Ariel

    2011-12-01

    The kidney is a highly vascularized organ that normally receives a fifth of the cardiac output. The unique spatial arrangement of the kidney vasculature with each nephron is crucial for the regulation of renal blood flow, GFR, urine concentration, and other specialized kidney functions. Thus, the proper and timely assembly of kidney vessels with their respective nephrons is a crucial morphogenetic event leading to the formation of a functioning kidney necessary for independent extrauterine life. Mechanisms that govern the development of the kidney vasculature are poorly understood. In this review, we discuss the anatomical development, embryological origin, lineage relationships, and key regulators of the kidney arterioles and postglomerular circulation. Because renal disease is associated with deterioration of the kidney microvasculature and/or the reenactment of embryonic pathways, understanding the morphogenetic events and processes that maintain the renal vasculature may open new avenues for the preservation of renal structure and function and prevent the progression of renal disease.

  17. Benidipine dilates both pre- and post-glomerular arteriole in the canine kidney.

    PubMed

    Yue, W; Kimura, S; Fujisawa, Y; Tian, R; Li, F; Rahman, M; Nishiyama, A; Fukui, T; Abe, Y

    2001-07-01

    The aim of the present study was to determine the effects of benidipine on renal function and whether benidipine may dilate the efferent arteriole as well as the afferent arteriole of the canine kidney. The effects of benidipine on the renal segmental vascular resistance were estimated using Gomez's formula with some modification. The renal hemodynamic action of benidipine was also compared with that of amlodipine. Intrarenal arterial injection of benidipine at a dose of 3 microg/kg resulted in a significant increase in renal blood flow (RBF), urine flow and urinary excretion of sodium, but not in glomerular filtration rate (GFR). Amlodipine at a dose of 300 microg/kg also increased RBF, urine flow and urinary excretion of sodium to a significant degree equivalent to that by benidipine. However, in contrast to benidipine, amlodipine significantly increased GFR. After the administration of benidipine, autoregulation of RBF and GFR was relatively maintained and the renal perfusion pressure (RPP)-RBF relation shifted upward; that is, RBFs at 75 and 50 mmHg were maintained at a higher level than those of the control. In contrast to benidipine, amlodipine diminished the autoregulation of RBF and GFR. RBFs at 75 and 50 mmHg were not different from those of the control. The afferent and efferent arteriolar resistance (Ra and Re) were calculated based on the RPP-RBF and RPP-GFR relations. Benidipine reduced both Ra and Re, but amlodipine selectively reduced Ra. Benidipine increased RBF but not GFR via the dilation of both afferent and efferent arterioles. Thus, benidipine has unique renal hemodynamic actions which differ from those by most calcium antagonists.

  18. Diaphragm arterioles are less responsive to alpha1- adrenergic constriction than gastrocnemius arterioles.

    PubMed

    Aaker, Aaron; Laughlin, M H

    2002-05-01

    The sympathetic nervous system has greater influence on vascular resistance in low-oxidative, fast-twitch skeletal muscle than in high-oxidative skeletal muscle (17). The purpose of this study was to test the hypothesis that arterioles isolated from low-oxidative, fast-twitch skeletal muscle [the white portion of gastrocnemius (WG)] possess greater responsiveness to adrenergic constriction than arterioles isolated from high-oxidative skeletal muscle [red portion of the gastrocnemius muscle (RG) and diaphragm (Dia)]. Second-order arterioles (2As) were isolated from WG, RG, and Dia of rats and reactivity examined in vitro. Results reveal that Dia 2As constrict less to norepinephrine (NE) (10(-9) to 10 (-4) M) than 2As from RG and WG, which exhibited similar NE-induced constrictions. This difference was not endothelium dependent, because responses of denuded 2As were similar to those of intact arterioles. The blunted NE-induced constrictor response of Dia 2As appears to be the result of differences in alpha1-receptor effects because 1) arterioles from Dia also responded less to selective alpha1-receptor stimulation with phenylephrine than RG and WG arterioles; 2) arterioles from Dia, RG, and WG dilated similarly to isoproterenol (10(-9) to 10(-4) M) and did not respond to selective alpha2-receptor stimulation with UK-14304; and 3) endothelin-1 produced similar constriction in 2As from Dia, RG, and WG. We conclude that differences in oxidative capacity and/or fiber type composition of muscle tissue do not explain different NE responsiveness of Dia 2As compared with 2As from gastrocnemius muscle. Differences in alpha1-adrenergic constrictor responsiveness among arterioles in skeletal muscle may contribute to nonuniform muscle blood flow responses observed during exercise and serve to maintain blood flow to Dia during exercise-induced increases in sympathetic nerve activity.

  19. SOD1 Limits Renal Microvascular Remodeling and Attenuates Arteriole and Blood Pressure Responses to Angiotensin II via Modulation of Nitric Oxide Bioavailability

    PubMed Central

    Carlström, Mattias; Lai, En Yin; Ma, Zufu; Steege, Andreas; Patzak, Andreas; Eriksson, Ulf J.; Lundberg, Jon O.; Wilcox, Christopher S.; Persson, A. Erik G.

    2011-01-01

    Oxidative stress is associated with vascular remodeling and increased preglomerular resistance that are both implicated in the pathogenesis of renal and cardiovascular disease. Angiotensin II induces superoxide production which is metabolized by superoxide dismutase (SOD) or scavenged by nitric oxide. We investigated the hypothesis that SOD1 regulates renal microvascular remodeling, blood pressure and arteriolar responsiveness and sensitivity to angiotensin II, using SOD1-transgenic (SOD1-tg) and SOD1-knockout (SOD1-ko) mice. Blood pressure, measured telemetrically, rose more abruptly during prolonged angiotensin II infusion in SOD1-ko mice. The afferent arteriole media-to-lumen ratios were reduced in SOD1-tg and increased in SOD1-ko mice. Afferent arterioles from non-treated wild-types had graded contraction to angiotensin II (sensitivity: 10-9 mol/l, responsiveness: 40%). Angiotensin II contraction were less sensitive (10-8 mol/l) and responsive (14%) in SOD1-tg, but more sensitive (10-13 mol/l) and responsive (89%) in SOD1-ko mice. Arterioles from SOD1-ko had 4-fold increased superoxide formation with angiotensin II at 10-9 mol/l. L-NAME reduced arteriole diameter of SOD1-tg, and enhanced angiotensin II sensitivity and responsiveness of wild-type and SOD1-tg to the level of SOD1-ko mice. Tempol increased arteriole diameter and normalized the enhanced sensitivity and responsiveness to angiotensin II of SOD1-ko, but did not affect wild-type or SOD1-tg mice. Neither SOD1-deficiency nor overexpression was associated with changes in nitrate/nitrite excretion, or renal mRNA expression of NOS-, NADPH oxidase-, SOD2/SOD3-isoforms, and angiotensin II receptors. In conclusion, SOD1 limits afferent arteriole remodeling and reduces sensitivity and responsiveness to angiotensin II by reducing superoxide and maintaining nitric oxide bioavailability. This may prevent an early and exaggerated blood pressure response to angiotensin II. PMID:20876452

  20. Intracellular ATP can regulate afferent arteriolar tone via ATP-sensitive K+ channels in the rabbit.

    PubMed Central

    Lorenz, J N; Schnermann, J; Brosius, F C; Briggs, J P; Furspan, P B

    1992-01-01

    Studies were performed to assess whether ATP-sensitive K+ (KATP) channels on rabbit preglomerular vessels can influence afferent arteriolar (AA) tone. K+ channels with a slope conductance of 258 +/- 13 (n = 7) pS and pronounced voltage dependence were demonstrated in excised patches from vascular smooth muscle cells of microdissected preglomerular segments. Channel activity was markedly reduced by 1 mM ATP and in a dose-dependent fashion by glibenclamide (10(-9) M to 10(-6) M), a specific antagonist of KATP channels. 10(-5) M diazoxide, a K+ channel opener, activated these channels in the presence of ATP, and this effect was also blocked by glibenclamide. To determine the role of these KATP channels in the control of vascular tone, diazoxide was tested on isolated perfused AA. After preconstriction from a control diameter of 13.1 +/- 1.1 to 3.5 +/- 2.1 microns with phenylephrine (PE), addition of 10(-5) M diazoxide dilated vessels to 11.2 +/- 0.7 microns, which was not different from control. Further addition of 10(-5) M glibenclamide reconstricted the vessels to 5.8 +/- 1.5 microns (n = 5; P less than 0.03). In support of its specificity for KATP channels, glibenclamide did not reverse verapamil induced dilation in a separate series of experiments. To determine whether intracellular ATP levels can effect AA tone, studies were conducted to test the effect of the glycolytic inhibitor 2-deoxy-D-glucose. After preconstriction from 13.4 +/- 3.2 to 7.7 +/- 1.3 microns with PE, bath glucose was replaced with 6 mM 2-deoxy-D-glucose. Within 10 min, the arteriole dilated to a mean value of 11.8 +/- 1.4 microns (n = 6; NS compared to control). Subsequent addition of 10(-5) M glibenclamide significantly reconstricted the vessels to a diameter of 8.6 +/- 0.5 micron (P less than 0.04). These data demonstrate that KATP channels are present on the preglomerular vasculature and that changes in intracellular ATP can directly influence afferent arteriolar tone via these channels

  1. Stenosis differentially affects subendocardial and subepicardial arterioles in vivo.

    PubMed

    Merkus, D; Vergroesen, I; Hiramatsu, O; Tachibana, H; Nakamoto, H; Toyota, E; Goto, M; Ogasawara, Y; Spaan, J A; Kajiya, F

    2001-04-01

    The presence of a coronary stenosis results primarily in subendocardial ischemia. Apart from the decrease in coronary perfusion pressure, a stenosis also decreases coronary flow pulsations. Applying a coronary perfusion system, we compared the autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12) arterioles (<120 microm) after stepwise decreases in coronary arterial pressure from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were performed with and without stenosis on the perfusion line. Maximal arteriolar diameter during the cardiac cycle was determined and normalized to its value at 100 mmHg. The initial decrease in diameter during reductions in pressure was significantly larger at the subendocardium. Diameters of subendocardial and subepicardial arterioles were similar 10--15 s after the decrease in pressure without stenosis. However, stenosis decreased the dilatory response of the subendocardial arterioles significantly. This decreased dilatory response was also evidenced by a lower coronary inflow at similar average pressure in the presence of a stenosis. Inhibition of nitric oxide production with N(G)-monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude that the decrease in pressure caused by a stenosis in vivo results in a larger decrease in diameter of the subendocardial arterioles than in the subepicardial arterioles, and furthermore stenosis selectively decreases the dilatory response of subendocardial arterioles. These two findings expand our understanding of subendocardial vulnerability to ischemia.

  2. Distinct modulation of superficial and juxtamedullary arterioles by prostaglandin in vivo.

    PubMed

    Matsuda, Hiroto; Hayashi, Koichi; Arakawa, Koki; Kubota, Eiji; Honda, Masanori; Tokuyama, Hirobumi; Suzuki, Hiromichi; Yamamoto, Tokunori; Kajiya, Fumihiko; Saruta, Takao

    2002-11-01

    Renal afferent (AFF) and efferent arteriolar (EFF) responsiveness to angiotensin II (ANG II) in superficial and juxtamedullary nephrons in vivo remains undetermined, nor has it been clarified what role intrarenal autocrines/paracrines play in modulating the renal microvascular response. The present study characterized the responsiveness to ANG II (1-30 ng/kg/min) of AFF and EFF of canine superficial and juxtamedullary nephrons under pentobarbital anesthesia, using intravital CCD-videomicroscopy that allowed direct in vivo visualization of the renal microcirculation. Furthermore, the effect of prostaglandins (PG) and nitric oxide (NO) on ANG II-induced tone was examined. In superficial nephrons, ANG II induced a similar dose-dependent constriction of both AFF (46 +/- 5% constriction) and EFF (53 +/- 3%). In juxtamedullary arterioles, ANG II induced a dose-dependent constriction of EFF, whereas AFF responses were diminished (17 +/- 4% vs. 37 +/- 4% at 10 ng/kg/min). The PG inhibition by indomethacin enhanced the ANG II-induced constriction of juxtamedullary AFF, whereas no augmentation was observed in other arterioles. In contrast, NO inhibition by nitro-L-arginine methylester (L-NAME) enhanced the ANG II-induced constriction, with greater augmentation in juxtamedullary AFF and EFF. Finally, renal interstitial PG and nitrite/nitrate contents were greater in the medulla than the superficial cortex under basal and ANG II-stimulated conditions. Taken together, the results of the intravital CCD-videomicroscopy reveal that the renal microvascular action of ANG II had both zonal (juxtamedullary vs. superficial nephrons) and segmental (AFF vs. EFF) heterogeneity under the present experimental conditions. This heterogeneity was associated with a difference in the intrarenal production of prostaglandin E2 (PGE2) and NO; PGE2 contributed to segmental and zonal differences whereas NO was responsible for the zonal heterogeneity in arteriolar responsiveness.

  3. Regional differences in oxygen saturation in retinal arterioles and venules.

    PubMed

    Heitmar, Rebekka; Safeen, Saima

    2012-10-01

    Retinal vessel oxygenation saturation measurements have been the focus of much attention in recent years as a potential diagnostic parameter in a number of ocular and systemic pathologies. This interest has been heightened by the ability to measure oxygen saturation in vivo using a photographic technique. Retinal vessel oxygenation in venules and arterioles of 279 retinal vessels of 12 healthy Caucasian participants (mean age: 30 SD (+/- 6) years) were measured consecutively three times to evaluate short-term variation in oxygen saturation and regional variability of retinal vessel oxygen saturation using dual-wavelength technology (Oxymetry Modul, Imedos, Germany). All subjects underwent standard optometric assessment including non-contact intra-ocular pressure assessment as well as having their systemic blood pressure measured. Vessels were grouped as either near-macula or peripheral, depending on their location. Peripheral arterioles and venules exhibited significantly lower oxygen saturation compared to their near-macula counterparts (arterioles: 94.7% (SD 3.9) vs. 99.7% (SD 3.2); venules: 65.1% (SD 7.2) vs. 90.3% (SD 6.7)). Both arterioles and venules, main branches, and those feeding and draining the retina near the macula and periphery showed low short-term variability of oxygen saturation (arterioles: COV 1.2-1.8%; venules: COV 2.9-4.9%). Retinal arterioles and venules exhibit low short-term variation of oxygen saturation in healthy subjects. Regional differences in oxygen saturation could be a potential useful marker for risk stratification and diagnostic purposes of area-specific retinal pathology such as age-related macula degeneration and diabetic maculopathy.

  4. Contribution of cytochrome P450 epoxygenase and hydroxylase pathways to afferent arteriolar autoregulatory responsiveness

    PubMed Central

    Imig, John D; Falck, John R; Inscho, Edward W

    1999-01-01

    Previous studies have demonstrated an important role for the cytochrome P450 (CYT-P450) pathway in afferent arteriole autoregulatory responses but the involvement of specific pathways remains unknown. Experiments were performed to determine the role of CYT-P450 epoxygenase and hydroxylase pathways in pressure mediated preglomerular autoregulatory responses.Afferent arteriolar diameter was measured as renal perfusion pressure was increased from 80–160 mmHg. Afferent arteriolar diameter averaged 19±2 μm at a renal perfusion pressure of 80 mmHg and decreased by 15±2% when pressure was increased to 160 mmHg.Inhibition of the epoxygenase pathway with 6-(2-proparglyloxyphenyl)hexanoic acid (PPOH), enhanced the microvascular response to increasing renal perfusion pressure. In the presence of 50 μM PPOH, afferent arteriolar diameter decreased by 29±4% when pressure was increased from 80–160 mmHg.Likewise, the sulphonimide derivative of PPOH, N-methylsulphonyl-6-(2-proparglyloxyphenyl) hexanamide (MS-PPOH, 50 μM), enhanced the afferent arteriolar response to increasing renal perfusion pressure.In contrast, the selective CYT-P450 hydroxylase inhibitor, N-methylsulphonyl-12,12-dibromododec-11-enamide (DDMS) attenuated the vascular response to increasing renal perfusion pressure. In the pressure of 25 μM DDMS, afferent arteriolar diameter decreased by 4±2% when pressure was increased from 80–160 mmHg.These results suggest that CYT-P450 metabolites of the epoxygenase pathway alter afferent arteriolar responsiveness and thereby modify the ability of the preglomerular vasculature to autoregulate renal blood flow. Additionally, these results provide further support to the concept that a metabolite of the hydroxylase pathway is an integral component of the afferent arteriolar response to elevations in perfusion pressure. PMID:10455289

  5. Differential adenosine sensitivity of diaphragm and skeletal muscle arterioles.

    PubMed

    Aaker, Aaron; Laughlin, M H

    2002-09-01

    The hyperemic response in exercising skeletal muscle is dependent on muscle fiber-type composition and fiber recruitment patterns, but the vascular control mechanisms producing exercise hyperemia in skeletal muscle remain poorly understood. The purpose of this study was to test the hypothesis that arterioles from white, low-oxidative skeletal muscle are less responsive to adenosine-induced dilation than are arterioles from diaphragm (Dia) and red, high-oxidative skeletal muscle. Second-order arterioles (2As) were isolated from the white portion of gastrocnemius muscle (WG; low-oxidative, fast-twitch muscle tissue) and two types of high-oxidative skeletal muscle [Dia and red portion of gastrocnemius muscle (RG)] of rats. Results reveal that 2As from all three types of muscle dilated in response to the endothelium-dependent dilator acetylcholine (WG: 48 +/- 3%, Dia: 51 +/- 3%, RG: 74 +/- 3%). In contrast, adenosine dilated only 2As from WG (48 +/- 4%) and Dia (46 +/- 5%) but not those from RG (5 +/- 5%). Thus adenosine-induced dilator responses differed among 2As of these different types of muscle tissue. However, the results do not support our hypothesis because 2As from Dia and WG dilated in response to adenosine, whereas 2As from RG did not. We conclude that the adenosine responsiveness of 2As from rat skeletal muscle cannot be predicted only by the fiber-type composition or oxidative capacity of the skeletal muscle tissue wherein the arteriole lies.

  6. Cerebellar and afferent ataxias.

    PubMed

    Pandolfo, Massimo; Manto, Mario

    2013-10-01

    Ataxia is the predominant manifestation of many acquired and inherited neurologic disorders affecting the cerebellum, its connections, and the afferent proprioceptive pathways. This article reviews the phenomenology and etiologies of cerebellar and afferent ataxias and provides indications for a rational approach to diagnosis and management. The pathophysiology of ataxia is being progressively understood and linked to the functional organization of the cerebellum. The impact of cerebellar diseases on different neurologic functions has been better defined and shown not to be limited to loss of motor coordination. The role of autoimmunity is increasingly recognized as a cause of sporadic cases of ataxia. Large collaborative studies of long duration are providing crucial information on the clinical spectrum and natural history of both sporadic ataxias (such as the cerebellar form of multiple system atrophy) and inherited ataxias. New dominant and recessive ataxia genes have been identified. On the therapeutic front, progress mostly concerns the development of treatments for Friedreich ataxia. Ataxia is the clinical manifestation of a wide range of disorders. In addition to accurate clinical assessment, MRI plays a major role in the diagnostic workup, allowing us to distinguish degenerative conditions from those due to other types of structural damage to the cerebellar or proprioceptive systems. Diagnostic algorithms based on clinical features, imaging, and neurophysiologic and biochemical parameters can be used to guide genetic testing for hereditary ataxias, the diagnosis of which is likely to be greatly improved by the introduction of new-generation DNA-sequencing approaches. Some rare forms of ataxia can be treated, so their diagnosis should not be missed. Proven symptomatic treatments for ataxia are still lacking, but intensive physical therapy appears to be helpful.

  7. Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

    NASA Technical Reports Server (NTRS)

    Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

    1990-01-01

    Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

  8. p47(phox) is required for afferent arteriolar contractile responses to angiotensin II and perfusion pressure in mice.

    PubMed

    Lai, En Yin; Solis, Glenn; Luo, Zaiming; Carlstrom, Mattias; Sandberg, Kathryn; Holland, Steven; Wellstein, Anton; Welch, William J; Wilcox, Christopher S

    2012-02-01

    Myogenic and angiotensin contractions of afferent arterioles generate reactive oxygen species. Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47(phox)/neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47(phox) enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47(phox) +/+ but not -/- mice increased renal cortical NADPH oxidase activity (7±1-12±1 [P<0.01] versus 5±1-7±1 10(3) · RLU · min(-1) · μg protein(-1) [P value not significant]), mean arterial pressure (77±2-91±2 [P<0.005] versus 74±2-77±1 mm Hg [P value not significant]), and renal vascular resistance (7.5±0.4-10.1±0.7 [P<0.01] versus 7.9±0.4-8.3±0.4 mm Hg/mL · min(-1) · gram kidney weight(-1) [P value not significant]). Afferent arterioles from p47(phox) -/- mice had a lesser myogenic response (3.1±0.4 versus 1.4±0.2 dynes · cm(-1) · mm Hg(-1); P<0.02) and a lesser (P<0.05) contraction to 10(-6) M angiotensin II (diameter change +/+: 9.3±0.2-3.4±0.6 μm versus -/-: 9.9±0.6-7.5±0.4 μm). Angiotensin and increased perfusion pressure generated significantly (P<0.05) more reactive oxygen species in p47(phox) +/+ than -/- arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47(phox) +/+ mice to 10(-6) M angiotensin II yet decreased the response in p47(phox) -/- mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47(phox) +/+ mice. We conclude that p47(phox) is required to enhance renal NADPH oxidase activity and basal afferent arteriolar myogenic and angiotensin II contractions and to switch afferent arteriolar tachyphylaxis to sensitization to angiotensin during a prolonged angiotensin infusion. These effects likely contribute to hypertension and renal vasoconstriction during infusion of angiotensin II.

  9. Sex-dependent expression of TRPV1 in bladder arterioles.

    PubMed

    Phan, Thieu X; Ton, Hoai T; Chen, Yue; Basha, Maureen E; Ahern, Gerard P

    2016-11-01

    Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1(PLAP-nlacZ)) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15-40 μm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca(2+) in ∼15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions.

  10. Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.

    PubMed

    Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro; Dacey, Ralph G

    2016-06-01

    We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH. Copyright © 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  11. Soluble epoxide hydrolase contamination of specific catalase preparations inhibits epoxyeicosatrienoic acid vasodilation of rat renal arterioles

    PubMed Central

    Olson, Lauren; Harder, Adam; Isbell, Marilyn; Imig, John D.; Gutterman, David D.; Falck, J. R.; Campbell, William B.

    2011-01-01

    Cytochrome P-450 metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs) and hydrogen peroxide (H2O2), are important signaling molecules in the kidney. In renal arteries, EETs cause vasodilation whereas H2O2 causes vasoconstriction. To determine the physiological contribution of H2O2, catalase is used to inactivate H2O2. However, the consequence of catalase action on EET vascular activity has not been determined. In rat renal afferent arterioles, 14,15-EET caused concentration-related dilations that were inhibited by Sigma bovine liver (SBL) catalase (1,000 U/ml) but not Calbiochem bovine liver (CBL) catalase (1,000 U/ml). SBL catalase inhibition was reversed by the soluble epoxide hydrolase (sEH) inhibitor tAUCB (1 μM). In 14,15-EET incubations, SBL catalase caused a concentration-related increase in a polar metabolite. Using mass spectrometry, the metabolite was identified as 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), the inactive sEH metabolite. 14,15-EET hydrolysis was not altered by the catalase inhibitor 3-amino-1,2,4-triazole (3-ATZ; 10–50 mM), but was abolished by the sEH inhibitor BIRD-0826 (1–10 μM). SBL catalase EET hydrolysis showed a regioisomer preference with greatest hydrolysis of 14,15-EET followed by 11,12-, 8,9- and 5,6-EET (Vmax = 0.54 ± 0.07, 0.23 ± 0.06, 0.18 ± 0.01 and 0.08 ± 0.02 ng DHET·U catalase−1·min−1, respectively). Of five different catalase preparations assayed, EET hydrolysis was observed with two Sigma liver catalases. These preparations had low specific catalase activity and positive sEH expression. Mass spectrometric analysis of the SBL catalase identified peptide fragments matching bovine sEH. Collectively, these data indicate that catalase does not affect EET-mediated dilation of renal arterioles. However, some commercial catalase preparations are contaminated with sEH, and these contaminated preparations diminish the biological activity of H2O2 and EETs. PMID:21753077

  12. Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke.

    PubMed

    Shih, Andy Y; Friedman, Beth; Drew, Patrick J; Tsai, Philbert S; Lyden, Patrick D; Kleinfeld, David

    2009-04-01

    Pial arterioles actively change diameter to regulate blood flow to the cortex. However, it is unclear whether arteriole reactivity and its homeostatic role of conserving red blood cell (RBC) flux remains intact after a transient period of ischemia. To examine this issue, we measured vasodynamics in pial arteriole networks that overlie the stroke penumbra during transient middle cerebral artery occlusion in rat. In vivo two-photon laser-scanning microscopy was used to obtain direct and repeated measurements of RBC velocity and lumen diameter of individual arterioles, from which the flux of RBCs was calculated. We observed that occlusion altered surface arteriole flow patterns in a manner that ensured undisrupted flow to penetrating arterioles throughout the imaging field. Small-diameter arterioles (<23 microm), which included 88% of all penetrating arterioles, exhibited robust vasodilation over a 90-min occlusion period. Critically, persistent vasodilation compensated for an incomplete recovery of RBC velocity during reperfusion to enable a complete restoration of postischemic RBC flux. Further, histologic examination of tissue hypoxia suggested re-oxygenation through all cortical layers of the penumbra. These findings indicate that selective reactivity of small pial arterioles is preserved in the stroke penumbra and acts to conserve RBC flux during reperfusion.

  13. Iodinated contrast media differentially affect afferent and efferent arteriolar tone and reactivity in mice: a possible explanation for reduced glomerular filtration rate.

    PubMed

    Liu, Zhi Z; Viegas, Vinicius U; Perlewitz, Andrea; Lai, En Y; Persson, Pontus B; Patzak, Andreas; Sendeski, Mauricio M

    2012-12-01

    To determine the effect of the iodinated contrast medium iodixanol on arteriolar tone in afferent and efferent arterioles of the glomerulus and the functional interactions with the major modulators of arteriolar tone, angiotensin II and nitric oxide, in mice. Animal handling conformed to the ethics guidelines of the Office for Health and Social Matters of Berlin. Arterioles were isolated from 136 C57BL/6 mice, perfused with either vehicle solution or iodixanol (23 mg of iodine per milliliter) for 20 minutes, followed by angiotensin II administration. Fluorescence of 3-amino-4-(N-methylamino)-2',7'-difluorofluorescein (DAF-FM) and dihydroethidium (DHE) were used for quantification of nitric oxide bioavailability and superoxide concentration, respectively. Statistical analysis of time- and dose-dependent data was performed by using the nonparametric test for repeated measurements. With iodixanol, afferent arteriole diameters were significantly reduced from 9.2 µm to 8.3 µm; in control group, the diameters were increased from 8.7 µm to 9.3 µm (P = .008). Nitric oxide synthase inhibition augmented iodixanol-induced constriction, with diameters reduced from 9.9 µm to 5.8 µm (P < .0001). DAF-FM fluorescence increased less during iodixanol treatment and nitric oxide synthase inhibition (3.6% and 3.7% vs 10.7% in control group, P = .009 and P = .049, respectively), indicating impaired nitric oxide bioavailability. With iodixanol, DHE fluorescence ratio was increased by 12% (P < .0001). Angiotensin II responses were enhanced by iodixanol and by nitric oxide synthase inhibition after perfusion with iodixanol (3.3 µm and 4.3 µm vs 7.5 µm [control group] with 1 × 10(-6)/mol/L angiotensin II, P = .03 for both). In contrast, in efferent arterioles, neither their basal diameters nor the responses to angiotensin II were significantly affected by iodixanol. A more pronounced effect of iodixanol on afferent than on efferent arterioles may contribute to the reduction of

  14. Plasma fibronectin promotes thrombus growth and stability in injured arterioles

    PubMed Central

    Ni, Heyu; Yuen, Peter S. T.; Papalia, Jessie M.; Trevithick, Jane E.; Sakai, Takao; Fässler, Reinhard; Hynes, Richard O.; Wagner, Denisa D.

    2003-01-01

    Mice lacking both of the best-known platelet ligands, von Willebrand factor and fibrinogen, can still form occlusive thrombi in injured arterioles. The platelets of these animals accumulate excessive amounts of fibronectin (FN). These observations led us to examine the contribution of plasma FN (pFN) to thrombus formation. Inactivation of the FN gene in FN conditional knockout mice reduced pFN levels to <2% and platelet FN to ≈20% of the levels in similarly treated control mice. The mice were then observed in a model of arterial injury to evaluate their capacity to form thrombi. The deficiency of pFN did not affect the initial platelet adhesion, but a delay of several minutes in thrombus formation was observed in the arterioles of pFN-deficient mice as compared with control mice. The thrombi that formed in the absence of pFN were stably anchored to the vessel wall but continuously shed platelets or small platelet clumps, thus slowing their growth significantly; the platelet/platelet cohesion was apparently diminished. Consequently the occlusion of pFN-deficient vessels was delayed, with the majority of vessels remaining patent at the end of the 40-min observation period. We conclude that, in addition to von Willebrand factor and fibrinogen, FN plays a significant role in thrombus initiation, growth, and stability at arterial shear rates and that deficiency in each of the three platelet ligands has its own specific impact on platelet plug formation. PMID:12606706

  15. Anatomy and Physiology of Phrenic Afferent Neurons.

    PubMed

    Nair, Jayakrishnan; Streeter, Kristi A; Turner, Sara M F; Sunshine, Michael D; Bolser, Donald C; Fox, Emily J; Davenport, Paul W; Fuller, David D

    2017-08-23

    Large diameter myelinated phrenic afferents discharge in phase with diaphragm contraction and smaller diameter fibers discharge across the respiratory cycle. In this article, we review the phrenic afferent literature and highlight areas in need of further study. We conclude that 1) activation of both myelinated and non-myelinated phrenic sensory afferents can influence respiratory motor output on a breath-by-breath basis; 2) the relative impact of phrenic afferents substantially increases with diaphragm work and fatigue; 3) activation of phrenic afferents has a powerful impact on sympathetic motor outflow, and 4) phrenic afferents contribute to diaphragm somatosensation and the conscious perception of breathing. Much remains to be learned regarding the spinal and supraspinal distribution and synaptic contacts of myelinated and non-myelinated phrenic afferents. Similarly, very little is known regarding the potential role of phrenic afferent neurons in triggering or modulating expression of respiratory neuroplasticity. Copyright © 2017, Journal of Neurophysiology.

  16. Reduced flow-and acetylcholine-induced dilations in visceral compared to subcutaneous adipose arterioles in human morbid obesity.

    PubMed

    Grizelj, Ivana; Cavka, Ana; Bian, Jing-Tan; Szczurek, Mary; Robinson, Austin; Shinde, Shruti; Nguyen, Van; Braunschweig, Carol; Wang, Edward; Drenjancevic, Ines; Phillips, Shane A

    2015-01-01

    The hypothesis of this study was that microvascular FID and AChID is impaired in visceral (VAT) compared to SAT arterioles in morbidly obese women. An Additional aim was to determine the mechanisms contributing to FID and AChID in VAT and SAT arterioles. Arterioles were obtained from SAT and VAT biopsies from women (BMI > 35 kg/m(2) ) undergoing bariatric surgery. Microvessels were cannulated for reactivity measurements in response to flow (pressure gradients of 10-100 cmH2 O) and to ACh (10(-9) -10(-4 ) M) with and without l-NAME, INDO, and PEG-catalase. NO and H2 O2 generation were detected in arterioles by fluorescence microscopy. FID and AChID of arterioles from VAT were reduced compared to SAT arterioles. In SAT arterioles, l-NAME, INDO, and PEG-catalase significantly reduced FID and AChID but had no effect individually on VAT arterioles' vasodilator reactivity. INDO +l-NAME reduced FID in VAT arterioles. NO-fluorescence was greater in arterioles from SAT compared to VAT arterioles. Vascular H2 O2 generation during flow was similar in both VAT and SAT. Our results suggest that VAT arterioles display reduced vasodilator reactivity to flow and ACh compared to SAT arterioles, mediated by different regulatory mechanisms in human obesity. © 2014 John Wiley & Sons Ltd.

  17. Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles

    PubMed Central

    LeBlanc, AJ; Chen, B; Dougherty, PJ; Reyes, RA; Shipley, RD; Korzick, DH; Muller-Delp, JM

    2012-01-01

    The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age. PMID:23198990

  18. Pharmacology of airway afferent nerve activity

    PubMed Central

    Undem, Bradley J; Carr, Michael J

    2001-01-01

    Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens) and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology. PMID:11686889

  19. Arachidonic Acid–Induced Dilation in Human Coronary Arterioles: Convergence of Signaling Mechanisms on Endothelial TRPV4‐Mediated Ca2+ Entry

    PubMed Central

    Zheng, Xiaodong; Zinkevich, Natalya S.; Gebremedhin, Debebe; Gauthier, Kathryn M.; Nishijima, Yoshinori; Fang, Juan; Wilcox, David A.; Campbell, William B.; Gutterman, David D.; Zhang, David X.

    2013-01-01

    Background Arachidonic acid (AA) and/or its enzymatic metabolites are important lipid mediators contributing to endothelium‐derived hyperpolarizing factor (EDHF)–mediated dilation in multiple vascular beds, including human coronary arterioles (HCAs). However, the mechanisms of action of these lipid mediators in endothelial cells (ECs) remain incompletely defined. In this study, we investigated the role of the transient receptor potential vanilloid 4 (TRPV4) channel in AA‐induced endothelial Ca2+ response and dilation of HCAs. Methods and Results AA induced concentration‐dependent dilation in isolated HCAs. The dilation was largely abolished by the TRPV4 antagonist RN‐1734 and by inhibition of endothelial Ca2+‐activated K+ channels. In native and TRPV4‐overexpressing human coronary artery ECs (HCAECs), AA increased intracellular Ca2+ concentration ([Ca2+]i), which was mediated by TRPV4‐dependent Ca2+ entry. The AA‐induced [Ca2+]i increase was inhibited by cytochrome P450 (CYP) inhibitors. Surprisingly, the CYP metabolites of AA, epoxyeicosatrienoic acids (EETs), were much less potent activators of TRPV4, and CYP inhibitors did not affect EET production in HCAECs. Apart from its effect on [Ca2+]i, AA induced endothelial hyperpolarization, and this effect was required for Ca2+ entry through TRPV4. AA‐induced and TRPV4‐mediated Ca2+ entry was also inhibited by the protein kinase A inhibitor PKI. TRPV4 exhibited a basal level of phosphorylation, which was inhibited by PKI. Patch‐clamp studies indicated that AA activated TRPV4 single‐channel currents in cell‐attached and inside‐out patches of HCAECs. Conclusions AA dilates HCAs through a novel mechanism involving endothelial TRPV4 channel‐dependent Ca2+ entry that requires endothelial hyperpolarization, PKA‐mediated basal phosphorylation of TRPV4, and direct activation of TRPV4 channels by AA. PMID:23619744

  20. Direct observations of muscle arterioles and venules following contraction of skeletal muscle fibres in the rat.

    PubMed Central

    Marshall, J M; Tandon, H C

    1984-01-01

    Direct observations have been made of responses of individual arterioles and venules of rat spinotrapezius muscle to contraction of the skeletal muscle fibres. Stimuli of 4-6 V intensity, 0.1 ms duration, delivered via a micro-electrode inserted into the spinotrapezius, evoked contraction of a small bundle of skeletal muscle fibres, followed by vasodilatation which was limited to all those arterioles and venules which crossed or ran alongside activated muscle fibres. Since venules outside the region of contraction, but supplied by dilating arterioles, were not passively distended by the attendant rise in intravascular pressure, it is concluded that both the arterioles and venules dilated actively in response to muscle contraction. All arterioles responded to a single twitch contraction, the terminal arterioles (7-13 micron i.d.) showing the largest increase in diameter. Collecting venules (9-18 micron i.d.) responded to just two twitches in 1 s and larger venules to five twitches in 1 s. When twitch contractions were continuously evoked for 10 s, the responses in individual arterioles and venules were graded with twitch frequency, the fastest and largest response occurring at 6-8 Hz. Tetanic contraction, at 40 Hz for 1 s, produced faster responses in all vessels, a maximum 55% increase from resting internal diameter being attained in only 8 s in some terminal arterioles. In all vessels the responses to tetanic contraction were equal to the maximal dilatation induced by papaverine. These results, in contrast with conclusions drawn from indirect estimates of venous responses, show that venules, like arterioles, dilate actively in response to muscle contraction. Venule dilatation may reduce the rise in capillary hydrostatic pressure, thereby limiting the outward filtration of fluid. PMID:6747856

  1. Arterioles in the swimming muscles of the leatherjacket Parika scaber (Pisces: Balistidae).

    PubMed

    Davison, W

    1987-06-01

    The leatherjacket (Parika scaber) is a balistiform fish which swims using its dorsal and anal median fins. The muscles controlling these fins are well vascularised, with control of blood flow effected by arterioles. These arterioles are long with a single layer of smooth muscle surrounding the endothelium, although the amount of contractile material is sparse, probably a consequence of the low blood pressure. The endothelial cells contain microfilaments, probably contractile, running along the length of the arteriole. The function of this material is unknown.

  2. Sensing vascular distension in skeletal muscle by slow conducting afferent fibers: neurophysiological basis and implication for respiratory control.

    PubMed

    Haouzi, Philippe; Chenuel, Bruno; Huszczuk, Andrew

    2004-02-01

    This review examines the evidence that skeletal muscles can sense the status of the peripheral vascular network through group III and IV muscle afferent fibers. The anatomic and neurophysiological basis for such a mechanism is the following: 1) a significant portion of group III and IV afferent fibers have been found in the vicinity and the adventitia of the arterioles and the venules; 2) both of these groups of afferent fibers can respond to mechanical stimuli; 3) a population of group III and IV fibers stimulated during muscle contraction has been found to be inhibited to various degrees by arterial occlusion; and 4) more recently, direct evidence has been obtained showing that a part of the group IV muscle afferent fibers is stimulated by venous occlusion and by injection of vasodilatory agents. The physiological relevance of sensing local distension of the vascular network at venular level in the muscles is clearly different from that of the large veins, since the former can directly monitor the degree of tissue perfusion. The possible involvement of this sensing mechanism in respiratory control is discussed mainly in the light of the ventilatory effects of peripheral vascular occlusions during and after muscular exercise. It is proposed that this regulatory system anticipates the chemical changes that would occur in the arterial blood during increased metabolic load and attempts to minimize them by adjusting the level of ventilation to the level of muscle perfusion, thus matching the magnitudes of the peripheral and pulmonary gas exchange.

  3. Complex interactions of NO/cGMP/PKG systems on Ca2+ signaling in afferent arteriolar vascular smooth muscle

    PubMed Central

    Arendshorst, William J.

    2010-01-01

    Little is known about the effects of nitric oxide (NO) and the cyclic GMP (cGMP)/protein kinase G (PKG) system on Ca2+ signaling in vascular smooth muscle cells (VSMC) of resistance vessels in general and afferent arterioles in particular. We tested the hypotheses that cGMP-, Ca2+-dependent big potassium channels (BKCa2+) buffer the Ca2+ response to depolarization by high extracellular KCl and that NO inhibits adenosine diphosphoribose (ADPR) cyclase, thereby reducing the Ca2+-induced Ca2+ release. We isolated rat afferent arterioles, utilizing the magnetized microsphere method, and measured cytosolic Ca2+ concentration ([Ca2+]i) with fura-2, a preparation in which endothelial cells do not participate in [Ca2+]i responses. KCl (50 mM)-induced depolarization causes an immediate increase in [Ca2+]i of 151 nM. The blockers Nω-nitro-l-arginine methyl ester (of nitric oxide synthase), 1,2,4-oxodiazolo-[4,3-a]quinoxalin-1-one (ODQ, of guanylyl cyclase), KT-5823 (of PKG activation), and iberiotoxin (IBX, of BKCa2+ activity) do not alter the [Ca2+]i response to KCl, suggesting no discernible endogenous NO production under basal conditions. The NO donor sodium nitroprusside (SNP) reduces the [Ca2+]i response to 77 nM; IBX restores the response to control values. These data show that activation of BKCa2+ in the presence of NO/cGMP provides a brake on KCl-induced [Ca2+]i responses. Experiments with the inhibitor of cyclic ADPR 8-bromo-cyclic ADPR (8-Br-cADPR) and SNP + downstream inhibitors of PKG and BKCa2+ suggest that NO inhibits ADPR cyclase in intact arterioles. When we pretreat afferent arterioles with 8-bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP; 10 μM), the response to KCl is 143 nM. However, in the presence of both IBX and 8-Br-cGMP, we observe a surprising doubling of the [Ca2+]i response to KCl. In summary, we present evidence for effects of the NO/cGMP/PKG system to reduce [Ca2+]i, via activation of BKCa2+ and possibly by inhibition of ADPR cyclase

  4. Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles

    NASA Technical Reports Server (NTRS)

    Muller-Delp, Judy; Spier, Scott A.; Ramsey, Michael W.; Lesniewski, Lisa A.; Papadopoulos, Anthony; Humphrey, J. D.; Delp, Michael D.

    2002-01-01

    Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.

  5. Functional and Molecular Characterization of the Endothelin System in Retinal Arterioles

    PubMed Central

    Hein, Travis W.; Ren, Yi; Yuan, Zhaoxu; Xu, Wenjuan; Somvanshi, Sonal; Nagaoka, Taiji; Yoshida, Akitoshi; Kuo, Lih

    2009-01-01

    Purpose Activation of the endothelin (ET) system has been implicated in the pathogenesis of retinal ischemic disease. Although ET-1, the predominant endogenous isoform of ET, has been shown to cause constriction of retinal vessels, the expression and functional significance of its synthesis and the involved specific ET receptors in retinal arterioles remain unknown. The authors examined the roles of ETA and ETB receptors and of endothelin-converting enzyme (ECE)-1 in ET-1–induced vasomotor responses of single retinal arterioles. Methods To exclude systemic confounding effects, porcine retinal arterioles were isolated for vasoreactivity and molecular studies. Results Isolated and pressurized retinal arterioles developed basal tone and constricted in a manner dependent on concentration to ET-1. ET-1 precursor big ET-1 elicited time-dependent vasoconstriction over 20 minutes, which was blocked by the ECE-1 inhibitor phosphoramidon. ETA receptor antagonist BQ123 inhibited most (approximately 90%) of vasoconstrictions to ET-1 and big ET-1. ETB receptor agonist sarafotoxin also elicited concentration-dependent constriction of retinal arterioles but with significantly less potency than ET-1. ETB receptor antagonist BQ788 abolished vasoconstriction to sarafotoxin but only slightly reduced responses to ET-1 and big ET-1. Protein and mRNA expressions of ETA, ETB, and ECE-1 were detected in retinal arterioles. Immunohistochemistry revealed ETA and ETB receptors predominantly in smooth muscle and ECE-1 predominantly in endothelium and smooth muscle. Conclusions ET-1 elicits constriction of retinal arterioles predominantly through the activation of smooth muscle ETA receptors. Endogenous production of ET-1 from vascular ECE-1 is sufficient to evoke ETA receptor–dependent constriction in retinal arterioles. PMID:19151386

  6. Exercise-induced differential changes in gene expression among arterioles of skeletal muscles of obese rats

    PubMed Central

    Padilla, Jaume; Jenkins, Nathan T.; Thorne, Pamela K.; Martin, Jeffrey S.; Rector, R. Scott; Akter, Sadia; Davis, J. Wade

    2015-01-01

    Using next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty (OLETF) rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). We hypothesized that the greatest effects of exercise would be in the gastrocnemius arterioles. Results show that EX caused the largest number of changes in gene expression in the soleus and white gastrocnemius 2a arterioles with little to no changes in the feed arteries. In contrast, SPRINT caused substantial changes in gene expression in the feed arteries. IPA canonical pathway analysis revealed 18 pathways with significant changes in gene expression when analyzed across vessels and revealed that EX induces increased expression of the following genes in all arterioles examined: Shc1, desert hedgehog protein (Dhh), adenylate cyclase 4 (Adcy4), G protein binding protein, alpha (Gnat1), and Bcl2l1 and decreased expression of ubiquitin D (Ubd) and cAMP response element modulator (Crem). EX increased expression of endothelin converting enzyme (Ece1), Hsp90b, Fkbp5, and Cdcl4b in four of five arterioles. SPRINT had effects on expression of Crem, Dhh, Bcl2l1, and Ubd that were similar to EX. SPRINT also increased expression of Nfkbia, Hspa5, Tubb 2a and Tubb 2b, and Fkbp5 in all five arterioles and increased expression of Gnat1 in all but the soleus second-order arterioles. Many contractile and/or structural protein genes were increased by SPRINT in the gastrocnemius feed artery, but the same genes exhibited decreased expression in red gastrocnemius arterioles. We conclude that training-induced changes in arteriolar gene expression patterns differ by muscle fiber type composition and along the arteriolar tree. PMID:26183477

  7. Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles

    NASA Technical Reports Server (NTRS)

    Muller-Delp, Judy; Spier, Scott A.; Ramsey, Michael W.; Lesniewski, Lisa A.; Papadopoulos, Anthony; Humphrey, J. D.; Delp, Michael D.

    2002-01-01

    Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.

  8. Time course of vasodilatory responses in skeletal muscle arterioles: role in hyperemia at onset of exercise

    NASA Technical Reports Server (NTRS)

    Wunsch, S. A.; Muller-Delp, J.; Delp, M. D.

    2000-01-01

    At the onset of dynamic exercise, muscle blood flow increases within 1-2 s. It has been postulated that local vasodilatory agents produced by the vascular endothelium or the muscle itself contribute to this response. We hypothesized that only vasodilators that act directly on the vascular smooth muscle could produce vasodilation of skeletal muscle arterioles in <2 s. To test this hypothesis, we determined the time course of the vasodilatory response of isolated skeletal muscle arterioles to direct application of potassium chloride, adenosine, acetylcholine, and sodium nitroprusside. Soleus and gastrocnemius muscles were dissected from the hindlimbs of male Sprague-Dawley rats. First-order arterioles (100-200 microm) were isolated, cannulated on micropipettes, and pressurized to 60 cmH(2)O in an organ bath. Vasodilatory agents were added directly to the bath, and diameter responses of the arterioles were recorded in real time on a videotape recorder. Frame-by-frame analysis of the diameter responses indicated that none of the vasodilator agents tested produced significant diameter increases in <4 s in either soleus or gastrocnemius muscle arterioles. These results indicate that, although these local vasodilators produce significant vasodilation of skeletal muscle resistance arterioles, these responses are not rapid enough (within 1-2 s) to contribute to the initiation of the exercise hyperemic response at the onset of dynamic exercise.

  9. Effects of fiber composition and hindlimb unloading on the vasodilator properties of skeletal muscle arterioles.

    PubMed

    McCurdy, M R; Colleran, P N; Muller-Delp, J; Delp, M D

    2000-07-01

    It has been hypothesized that microgravity-induced orthostatic hypotension may result from an exaggerated vasodilatory responsiveness of arteries. The purpose of this study was to determine whether skeletal muscle arterioles exhibit enhanced vasodilation in rats after 2 wk of hindlimb unloading (HU). First-order arterioles isolated from soleus and white gastrocnemius muscles were tested in vitro for vasodilatory responses to isoproterenol (Iso), adenosine (Ado), and sodium nitroprusside (SNP). HU had no effect on responses induced by Iso but diminished maximal vasodilation to Ado and SNP in both muscles. In addition, vasodilatory responses in arterioles from control rats varied between muscle types. Maximal dilations induced by Iso (soleus: 42 +/- 6%; white gastrocnemius: 60 +/- 7%) and Ado (soleus: 51 +/- 8%; white gastrocnemius: 81 +/- 6%) were greater in arterioles from white gastrocnemius muscles. These data do not support the hypothesis that microgravity-induced orthostatic hypotension results from an enhanced vasodilatory responsiveness of skeletal muscle arterioles. Furthermore, the data support the concept that dilatory responsiveness of arterioles varies in muscle composed of different fiber types.

  10. Time course of vasodilatory responses in skeletal muscle arterioles: role in hyperemia at onset of exercise

    NASA Technical Reports Server (NTRS)

    Wunsch, S. A.; Muller-Delp, J.; Delp, M. D.

    2000-01-01

    At the onset of dynamic exercise, muscle blood flow increases within 1-2 s. It has been postulated that local vasodilatory agents produced by the vascular endothelium or the muscle itself contribute to this response. We hypothesized that only vasodilators that act directly on the vascular smooth muscle could produce vasodilation of skeletal muscle arterioles in <2 s. To test this hypothesis, we determined the time course of the vasodilatory response of isolated skeletal muscle arterioles to direct application of potassium chloride, adenosine, acetylcholine, and sodium nitroprusside. Soleus and gastrocnemius muscles were dissected from the hindlimbs of male Sprague-Dawley rats. First-order arterioles (100-200 microm) were isolated, cannulated on micropipettes, and pressurized to 60 cmH(2)O in an organ bath. Vasodilatory agents were added directly to the bath, and diameter responses of the arterioles were recorded in real time on a videotape recorder. Frame-by-frame analysis of the diameter responses indicated that none of the vasodilator agents tested produced significant diameter increases in <4 s in either soleus or gastrocnemius muscle arterioles. These results indicate that, although these local vasodilators produce significant vasodilation of skeletal muscle resistance arterioles, these responses are not rapid enough (within 1-2 s) to contribute to the initiation of the exercise hyperemic response at the onset of dynamic exercise.

  11. Cytochrome P450 and cyclooxygenase metabolites contribute to the endothelin-1 afferent arteriolar vasoconstrictor and calcium responses.

    PubMed

    Imig, J D; Pham, B T; LeBlanc, E A; Reddy, K M; Falck, J R; Inscho, E W

    2000-01-01

    Arachidonic acid metabolites contribute to the endothelin-1 (ET-1)-induced decrease in renal blood flow, but the vascular sites of action are unknown. Experiments performed in vitro used the rat juxtamedullary nephron preparation combined with videomicroscopy. The response of afferent arterioles to ET-1 was determined before and after cytochrome P450 (CYP450) or cyclooxygenase (COX) inhibition. Afferent arteriolar diameter averaged 20+/-1 microm (n=17) at a renal perfusion pressure of 100 mm Hg. Superfusion with 0.001 to 10 nmol/L ET-1 caused a graded decrease in diameter of the afferent arteriole. Vessel diameter decreased by 30+/-2% and 41+/-2% in response to 1 and 10 nmol/L ET-1, respectively. The afferent arteriolar response to ET-1 was significantly attenuated during administration of the CYP450 hydroxylase inhibitor N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), such that afferent arteriolar diameter decreased by 19+/-3% and 22+/-3% in response to 1 and 10 nmol/L ET-1, respectively. COX inhibition also greatly attenuated the vasoconstriction elicited by ET-1, whereas the CYP450 epoxygenase inhibitor N-methylsulfonyl-6-(2-proparglyoxyphenyl) hexanamide enhanced the ET-1-mediated vascular response. Additional studies were performed using freshly isolated smooth muscle cells prepared from preglomerular microvessels. Renal microvascular smooth muscle cells were loaded with the calcium-sensitive dye fura 2 and studied by use of single-cell fluorescence microscopy. Basal renal microvascular smooth muscle cell [Ca(2+)](i) averaged 95+/-3 nmol/L (n=42). ET-1 (10 nmol/L) increased microvascular smooth muscle cell [Ca(2+)](i) to a peak value of 731+/-75 nmol/L before stabilizing at 136+/-8 nmol/L. Administration of DDMS or the COX inhibitor indomethacin significantly attenuated the renal microvascular smooth muscle cell calcium response to ET-1. These data demonstrate that CYP450 hydroxylase and COX arachidonic acid metabolites contribute importantly to the

  12. Juvenile growth reduces the influence of epithelial sodium channels on myogenic tone in skeletal muscle arterioles.

    PubMed

    Kang, Lori S; Masilamani, Shyama; Boegehold, Matthew A

    2016-12-01

    Previous studies have documented that rapid juvenile growth is accompanied by functional changes in the arteriolar endothelium, but much less is known about functional changes in arteriolar smooth muscle over this period. In this study, we investigate the possible contribution of epithelial sodium channels (ENaC) to the myogenic behaviour of arterioles at two stages of juvenile growth. The effects of the ENaC inhibitor benzamil on different levels of myogenic tone were studied in isolated gracilis muscle arterioles from rats aged 21-28 days ("weanlings") and 42-49 days ("juveniles"). ENaC subunit expression in the arteriolar wall was also determined, and the interaction between ENaC and nitric oxide (NO) in regulating vascular tone was explored by combined use of benzamil and N(G) -monomethyl-l-arginine (l-NMMA). At physiological pressures, both steady-state myogenic tone and the dynamic adjustments in this tone triggered by acute pressure changes were less in juvenile arterioles than in weanling arterioles. α, β and γ ENaC protein was present in arterioles at both ages, but benzamil only had an effect on myogenic tone in weanling arterioles. In these vessels, benzamil increased, rather than decreased, myogenic tone, and this effect was prevented by l-NMMA or endothelial removal. These findings suggest that although ENaC is present in gracilis muscle arterioles of both weanling and juvenile rats, it is not obligatory for the genesis of myogenic activity in these vessels at either age. However, ENaC activity can significantly modulate the level of myogenic tone through stimulation of endothelial NO release at an early stage of growth. © 2016 John Wiley & Sons Australia, Ltd.

  13. Effect of Red Blood Cells on Platelet Activation and Thrombus Formation in Tortuous Arterioles.

    PubMed

    Chesnutt, Jennifer K W; Han, Hai-Chao

    2013-01-01

    Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs) is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

  14. Reduced flow-and acetylcholine-induced dilations in visceral compared to subcutaneous adipose arterioles in human morbid obesity

    PubMed Central

    Grizelj, I.; Cavka, A.; Bian, J.T.; Szczurek, M.; Robinson, A.; Shinde, S.; Nguyen, V.; Braunschweig, C.; Wang, E.; Drenjancevic, I.; Phillips, S.A.

    2014-01-01

    Background and aims The hypothesis of this study was that microvascular flow-induced dilation (FID) and acetylcholine-induced dilation (AChID) is impaired in visceral (VAT) compared to subcutaneous adipose tissue (SAT) arterioles in morbidly obese women. Additional aim was to determine the mechanisms contributing to FID and AChID in VAT and SAT arterioles. Methods and results Arterioles were obtained from SAT and VAT biopsies from women (BMI>35 kg/m2) undergoing bariatric surgery. Microvessels were cannulated for reactivity measurements in response to flow (pressure gradients of 10–100 cmH2O) and to acetylcholine (ACh;10−9–10−4 M) with and without Nω-nitro-L-arginine methyl ester (L-NAME), indomethacin (INDO), and PEG-catalase. Nitric oxide (NO)and hydrogen peroxide (H2O2) generation were detected in arterioles by fluorescence microscopy. FID and AChID of arterioles from VAT were reduced compared to SAT arterioles. In SAT arterioles, L-NAME, INDO, and PEG-catalase significantly reduced FID and AChID but had no effect individually on VAT arterioles’ vasodilator reactivity. INDO+L-NAME reduced FID in VAT arterioles. NO-fluorescence was greater in arterioles from SAT compared to VAT arterioles. Vascular H2O2 generation during flow was similar in both VAT and SAT. Conclusion Our results suggest that VAT arterioles display reduced vasodilator reactivity to flow and ACh compared to SAT arterioles, mediated by different regulatory mechanisms in human obesity. PMID:25155427

  15. Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex

    PubMed Central

    Taylor, Zachary J; Hui, Edward S; Watson, Ashley N; Nie, Xingju; Deardorff, Rachael L; Jensen, Jens H; Helpern, Joseph A

    2015-01-01

    Small cerebral infarcts, i.e. microinfarcts, are common in the aging brain and linked to vascular cognitive impairment. However, little is known about the acute growth of these minute lesions and their effect on blood flow in surrounding tissues. We modeled microinfarcts in the mouse cortex by inducing photothrombotic clots in single penetrating arterioles. The resultant hemodynamic changes in tissues surrounding the occluded vessel were then studied using in vivo two-photon microscopy. We were able to generate a spectrum of infarct volumes by occluding arterioles that carried a range of blood fluxes. Those resulting from occlusion of high-flux penetrating arterioles (flux of 2 nL/s or higher) exhibited a radial outgrowth that encompassed unusually large tissue volumes. The gradual expansion of these infarcts was propagated by an evolving insufficiency in capillary flow that encroached on territories of neighboring penetrating arterioles, leading to the stagnation and recruitment of their perfusion domains into the final infarct volume. Our results suggest that local collapse of microvascular function contributes to tissue damage incurred by single penetrating arteriole occlusions in mice, and that a similar mechanism may add to pathophysiology induced by microinfarcts of the human brain. PMID:26661182

  16. Comparison of membrane electrical activity of cat gastric submucosal arterioles and venules.

    PubMed Central

    Morgan, K G

    1983-01-01

    Intracellular electrical recordings were made from arterioles and venules of the cat gastric submucosa. Spontaneous rhythmic fluctuations of the membrane potential were recorded in 54% of the venular preparations. Arteriolar cells showed no spontaneous activity. Excitatory junction potentials were recorded in arterioles but not venules after single shocks to the perivascular nerves. The amplitude of the excitatory junction potential was decreased in the presence of alpha-blockers. Repetitive stimulation of the perivascular nerve caused a biphasic electrical response of venular smooth muscle cells. The depolarizing component was decreased by alpha-adrenergic blockade and the hyperpolarizing component by beta-blockade. Venules contracted in response to smaller depolarizations than did arterioles. The voltage threshold for contraction of venular cells was similar to that for arteriolar cells but the venular cells were significantly more depolarized at rest than were the arteriolar cells. The difference in resting potential provides an explanation for the difference in sensitivity to electrical input. PMID:6663496

  17. Piezo2 expression in corneal afferent neurons.

    PubMed

    Bron, Romke; Wood, Rhiannon J; Brock, James A; Ivanusic, Jason J

    2014-09-01

    Recently, a novel class of mechanically sensitive channels has been identified and have been called Piezo channels. In this study, we explored Piezo channel expression in sensory neurons supplying the guinea pig corneal epithelium, which have well-defined modalities in this species. We hypothesized that a proportion of corneal afferent neurons express Piezo2, and that these neurons are neurochemically distinct from corneal polymodal nociceptors or cold-sensing neurons. We used a combination of retrograde tracing to identify corneal afferent neurons and double label in situ hybridization and/or immunohistochemistry to determine their molecular and/or neurochemical profile. We found that Piezo2 expression occurs in ∼26% of trigeminal ganglion neurons and 30% of corneal afferent neurons. Piezo2 corneal afferent neurons are almost exclusively non-calcitonin gene-related peptide (CGRP)-immunoreactive (-IR), medium- to large-sized neurons that are NF200-IR, suggesting they are not corneal polymodal nociceptors. There was no coexpression of Piezo2 and transient receptor potential cation channel subfamily M member 8 (TRPM8) transcripts in any corneal afferent neurons, further suggesting that Piezo2 is not expressed in corneal cold-sensing neurons. We also noted that TRPM8-IR or CGRP-IR corneal afferent neurons are almost entirely small and lack NF200-IR. Piezo2 expression occurs in a neurochemically distinct subpopulation of corneal afferent neurons that are not polymodal nociceptors or cold-sensing neurons, and is likely confined to a subpopulation of pure mechano-nociceptors in the cornea. This provides the first evidence in an in vivo system that Piezo2 is a strong candidate for a channel that transduces noxious mechanical stimuli. © 2014 Wiley Periodicals, Inc.

  18. Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension

    PubMed Central

    Zhao, Zhi-Min; Liu, Su-Xuan; Zhang, Guan-Xin; Yang, Fan; Wang, Yang; Wu, Feng; Zhao, Xian-Xian; Xu, Zhi-Yun

    2016-01-01

    While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH. PMID:27472464

  19. The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice.

    PubMed

    Husarek, Kathryn E; Katz, Paige S; Trask, Aaron J; Galantowicz, Maarten L; Cismowski, Mary J; Lucchesi, Pamela A

    2016-01-01

    Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin-angiotensin-aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT1R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT1R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II-AT1R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events.

  20. Status of cerebral penetrating arterioles has important implication to stroke penumbra evaluation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Li, Yuandong; Wang, Ruikang K.

    2017-02-01

    Cerebral penetrating arterioles (PAs) are structurally and functionally different from the pial arterioles, as they are an exception group from the collateral circulation. Previous study has demonstrated the PAs are the bottlenecks to the flow from the surface arteries to the deeper microcirculations. However, functional change in PAs after ischemia plays an important role in delivering blood from a highly collateralized pial arteriole network to capillaries. An ability to separately monitor PA flow dynamics is critical to understand flow redistribution mechanism during stroke and refine stroke treatment target. We use optical coherence tomography (OCT)-based microangiography (OMAG) to evaluate flow and velocity change in multiple PAs after middle cerebral artery occlusion (MCAO) in mice across a large cortex region, covering distal branches of arterioles and anastomosis. We also apply OCT-based tissue injury mapping (TIM) method to reveal the potential penumbra development within the imaging region, upon which we observed apparent differences of the PA flow dynamics between core and penumbra regions. Our results suggest that the flow dynamics of PAs can be an important factor regulating the stroke penumbra development, and that stimulatory treatment targeting PAs can be studied under the guidance of OMAG.

  1. Contribution of nitric oxide synthase isoforms to cholinergic vasodilation in murine retinal arterioles.

    PubMed

    Gericke, Adrian; Goloborodko, Evgeny; Sniatecki, Jan J; Steege, Andreas; Wojnowski, Leszek; Pfeiffer, Norbert

    2013-04-01

    Nitric oxide synthases (NOSs) are critically involved in regulation of ocular perfusion. However, the contribution of the individual NOS isoforms to vascular responses is unknown in the retina. Because some previous findings suggested an involvement of inducible nitric oxide synthase (iNOS) in the regulation of retinal vascular tone, a major goal of the present study was to examine the hypothesis that iNOS is involved in mediating cholinergic vasodilation responses of murine retinal arterioles. Another subject of this study was to test the contribution of the other two NOS isoforms, neuronal (nNOS) and endothelial NOS (eNOS), to cholinergic retinal arteriole responses. Expression of individual NOS isoforms was determined in murine retinal arterioles using real-time PCR. All three NOS isoforms were expressed in retinal arterioles. However, eNOS mRNA was found to be most, and iNOS mRNA least abundant. To examine the functional relevance of iNOS for mediating vascular responses, retinal vascular preparations from gene-targeted iNOS-deficient mice (iNOS-/-) and wild-type mice were studied in vitro. Changes in luminal vessel diameter in response to the thromboxane mimetic 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619), the endothelium-dependent vasodilator acetylcholine, and the nitric oxide donor nitroprusside were measured by video microscopy. To determine the contribution of individual NOS isoforms to cholinergic vasodilation responses, retinas from iNOS-/- and wild-type mice were incubated with Nω-nitro-l-arginine methyl ester (l-NAME), a non-isoform-selective inhibitor of NOS, 7-nitroindazole, a selective nNOS blocker and aminoguanidine, a selective iNOS inhibitor. U-46619 evoked concentration-dependent vasoconstriction that was similar in retinal arterioles from iNOS-/- and wild-type mice. In retinal arterioles preconstricted with U-46619, acetylcholine and nitroprusside produced dose-dependent dilation that did not differ between iNOS-/- and

  2. Curcumin mediates both dilation and constriction of peripheral arterioles via adrenergic receptors.

    PubMed

    Dewar, Anthony M; Clark, Richard A; Singer, Adam J; Frame, Mary D

    2011-08-01

    Curcumin has wound healing attributes mediated through a plethora of biological activities that in general are not ascribed to specific receptors. Recently, we have demonstrated that intravenous administration of curcumin limits burn injury progression in a rat model. As decreased microvascular perfusion is a central element of burn injury progression, we hypothesized that curcumin may induce vasodilation in peripheral arterioles, to improve perfusion. Using mucosal microcirculation as an in situ assay, cheek pouch tissue was exteriorized in anesthetized (phentobarbital 70 mg kg(-1) intraperitoneal) male hamsters (N=60) to observe the terminal feed arterioles (∼8 μm diameter) and the immediately upstream arcade arterioles (∼20 μm). Curcumin (10(-12)-10(-4) mol l(-1)) was applied dose-wise (micropipette, 60 seconds). Subnanomolar curcumin dilated, whereas micromolar doses constricted, the arterioles. For the terminal arteriole: vasodilation logEC(50) -10.3±0.2, peak dilation +39±1%; vasconstriction logEC(50) -8.0±0.4, peak constriction -14±2%. Simultaneous atropine (muscarinic antagonist) or PD142893 (endothelin antagonist) had no effect. Propranolol (β-adrenergic receptor (β-Ad) antagonist) enhanced constriction by removing the vasodilation response to curcumin. Phentolamine (α-adrenergic receptor (α-Ad) antagonist) enhanced dilation to curcumin by removing the vasoconstriction response. Thus, the curcumin vasomotor activity on microcirculation was α-Ad and β-Ad receptor-dependent and its net vasoactive effect was concentration- and time-dependent.

  3. Flicker-induced retinal arteriole dilation is reduced by ambient lighting.

    PubMed

    Noonan, Jonathan E; Dusting, Gregory J; Nguyen, Thanh T; Man, Ryan E K; Best, William J; Lamoureux, Ecosse L

    2014-08-07

    To investigate the impact of ambient room lighting on the magnitude of flicker light-induced retinal vasodilations in healthy individuals. Twenty healthy nonsmokers participated in a balanced 2 × 2 crossover study. Retinal vascular imaging was performed with the dynamic vessel analyzer under reduced or normal ambient lighting, then again after 20 minutes under the alternate condition. Baseline calibers of selected arteriole and venule segments were recorded in measurement units. Maximum percentage dilations from baseline during 20 seconds of luminance flicker were calculated from the mean of three measurement cycles. Within-subject differences were assessed by repeated measures analysis of variance with the assumption of no carryover effects and pairwise comparisons from the fitted model. Mean (SD) maximum arteriole dilations during flicker stimulation under reduced and normal ambient lighting were 4.8% (2.3%) and 4.1% (1.9%), respectively (P = 0.019). Maximum arteriole dilations were (mean ± 95% confidence interval) 0.7% ± 0.6% lower under normal ambient lighting compared with reduced lighting. Ambient lighting had no significant effect on maximum venular dilations during flicker stimulation or on the baseline calibers of arterioles or venules. Retinal arteriole dilation in response to luminance flicker stimulation is reduced under higher ambient lighting conditions. Reduced responses with higher ambient lighting may reflect reduced contrast between the ON and OFF flicker phases. Although it may not always be feasible to conduct studies under reduced lighting conditions, ambient lighting levels should be consistent to ensure that comparisons are valid. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  4. Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

    PubMed Central

    Arrick, Denise M.; Sun, Hong; Patel, Kaushik P.

    2011-01-01

    Decreased dilation of cerebral arterioles via an increase in oxidative stress may be a contributing factor in the pathogenesis of diabetes-induced complications leading to cognitive dysfunction and/or stroke. Our goal was to determine whether resveratrol, a polyphenolic compound present in red wine, has a protective effect on cerebral arterioles during type 1 diabetes (T1D). We measured the responses of cerebral arterioles in untreated and resveratrol-treated (10 mg·kg−1·day−1) nondiabetic and diabetic rats to endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase (NOS)-dependent agonists and to a NOS-independent agonist. In addition, we harvested brain tissue from nondiabetic and diabetic rats to measure levels of superoxide under basal conditions. Furthermore, we used Western blot analysis to determine the protein expression of eNOS, nNOS, SOD-1, and SOD-2 in cerebral arterioles and/or brain tissue from untreated and resveratrol-treated nondiabetic and diabetic rats. We found that T1D impaired eNOS- and nNOS-dependent reactivity of cerebral arterioles but did not alter NOS-independent vasodilation. While resveratrol did not alter responses in nondiabetic rats, resveratrol prevented T1D-induced impairment in eNOS- and nNOS-dependent vasodilation. In addition, superoxide levels were higher in brain tissue from diabetic rats and resveratrol reversed this increase. Furthermore, eNOS and nNOS protein were increased in diabetic rats and resveratrol produced a further increased eNOS and nNOS proteins. SOD-1 and SOD-2 proteins were not altered by T1D, but resveratrol treatment produced a decrease in SOD-2 protein. Our findings suggest that resveratrol restores vascular function and oxidative stress in T1D. We suggest that our findings may implicate an important therapeutic potential for resveratrol in treating T1D-induced cerebrovascular dysfunction. PMID:21666113

  5. Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles

    PubMed Central

    Donato, Anthony J; Lesniewski, Lisa A; Delp, Michael D

    2007-01-01

    Ageing is associated with increased leg vascular resistance and reductions in leg blood flow during rest and exercise, potentially predisposing older adults to a host of functional and cardiovascular complications. The purpose of these studies was to examine the effects and possible mechanisms of ageing and exercise training on arteriolar adrenergic vasoreactivity. Young and old male Fischer 344 rats were divided into young sedentary (YS), old sedentary (OS), young exercise-trained (YT) or old exercise-trained (OT) groups, where training consisted of chronic treadmill exercise. Isolated soleus (SOL) and gastrocnemius (GAS) muscle arterioles were studied in vitro. Responses to noradrenaline in endothelium-intact and endothelium-denuded arterioles, as well as during nitric oxide synthase (NOS) inhibition were determined. Vasodilator responses to isoproterenol and forskolin were also determined. Results: Noradrenaline-mediated vasoconstriction was increased in SOL arterioles with ageing, and exercise training in old rats attenuated α-adrenergic vasoconstriction in arterioles from both muscle types. Removal of the endothelium and NOS inhibition eliminated these ageing and training effects. Isoproterenol-mediated vasodilatation was impaired with ageing in SOL and GAS arterioles, and exercise training had little effect on this response. Forskolin-induced vasodilatation was not affected by age. The data demonstrate that ageing augments α-adrenergic vasoconstriction while exercise training attenuates this response, and both of these alterations are mediated through an endothelial α-receptor-NOS-signalling pathway. In contrast, ageing diminishes β-receptor-mediated vasodilatation, but this impairment is specific to the smooth muscle. These studies indicate that α- and β-adrenergic mechanisms may serve to increase systemic vascular resistance with ageing, and that the effects of exercise training on adrenergic vasomotor properties could contribute to the beneficial

  6. Spinal cord thermosensitivity: An afferent phenomenon?

    PubMed Central

    Brock, James A.; McAllen, Robin M.

    2016-01-01

    ABSTRACT We review the evidence for thermoregulatory temperature sensors in the mammalian spinal cord and reach the following conclusions. 1) Spinal cord temperature contributes physiologically to temperature regulation. 2) Parallel anterolateral ascending pathways transmit signals from spinal cooling and spinal warming: they overlap with the respective axon pathways of the dorsal horn neurons that are driven by peripheral cold- and warm-sensitive afferents. 3) We hypothesize that these ‘cold’ and ‘warm’ ascending pathways transmit all extracranial thermosensory information to the brain. 4) Cutaneous cold afferents can be activated not only by cooling the skin but also by cooling sites along their axons: we consider that this is functionally insignificant in vivo. 5) By a presynaptic action on their central terminals, local spinal cooling enhances neurotransmission from incoming ‘cold’ afferent action potentials to second order neurons in the dorsal horn; this effect disappears when the spinal cord is warm. 6) Spinal warm sensitivity is due to warm-sensitive miniature vesicular transmitter release from afferent terminals in the dorsal horn: this effect is powerful enough to excite second order neurons in the ‘warm’ pathway independently of any incoming sensory traffic. 7) Distinct but related presynaptic mechanisms at cold- and warm-sensitive afferent terminals can thus account for the thermoregulatory actions of spinal cord temperature. PMID:27857953

  7. Afferent Connectivity of the Zebrafish Habenulae

    PubMed Central

    Turner, Katherine J.; Hawkins, Thomas A.; Yáñez, Julián; Anadón, Ramón; Wilson, Stephen W.; Folgueira, Mónica

    2016-01-01

    The habenulae are bilateral nuclei located in the dorsal diencephalon that are conserved across vertebrates. Here we describe the main afferents to the habenulae in larval and adult zebrafish. We observe afferents from the subpallium, nucleus rostrolateralis, posterior tuberculum, posterior hypothalamic lobe, median raphe; we also see asymmetric afferents from olfactory bulb to the right habenula, and from the parapineal to the left habenula. In addition, we find afferents from a ventrolateral telencephalic nucleus that neurochemical and hodological data identify as the ventral entopeduncular nucleus (vENT), confirming and extending observations of Amo et al. (2014). Fate map and marker studies suggest that vENT originates from the diencephalic prethalamic eminence and extends into the lateral telencephalon from 48 to 120 hour post-fertilization (hpf). No afferents to the habenula were observed from the dorsal entopeduncular nucleus (dENT). Consequently, we confirm that the vENT (and not the dENT) should be considered as the entopeduncular nucleus “proper” in zebrafish. Furthermore, comparison with data in other vertebrates suggests that the vENT is a conserved basal ganglia nucleus, being homologous to the entopeduncular nucleus of mammals (internal segment of the globus pallidus of primates) by both embryonic origin and projections, as previously suggested by Amo et al. (2014). PMID:27199671

  8. Electrophysiological characterization of human rectal afferents

    PubMed Central

    Ng, Kheng-Seong; Brookes, Simon J.; Montes-Adrian, Noemi A.; Mahns, David A.

    2016-01-01

    It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and “inflammatory soup” (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3–25) spikes/s vs. 2 (1–4), P < 0.001] and IS [median 5 (range 2–18) spikes/s vs. 2 (1–4), P < 0.001]. Mechanosensitive “hot spots” were identified in 16 nerves [median threshold 2.0 g (range 1.4–6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4–1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states. PMID:27789454

  9. Electrophysiological characterization of human rectal afferents.

    PubMed

    Ng, Kheng-Seong; Brookes, Simon J; Montes-Adrian, Noemi A; Mahns, David A; Gladman, Marc A

    2016-12-01

    It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and "inflammatory soup" (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3-25) spikes/s vs. 2 (1-4), P < 0.001] and IS [median 5 (range 2-18) spikes/s vs. 2 (1-4), P < 0.001]. Mechanosensitive "hot spots" were identified in 16 nerves [median threshold 2.0 g (range 1.4-6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4-1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states. Copyright © 2016 the American Physiological Society.

  10. Steady-State Free Ca(2+) in Astrocytes Is Decreased by Experience and Impacts Arteriole Tone.

    PubMed

    Mehina, Eslam M F; Murphy-Royal, Ciaran; Gordon, Grant R

    2017-08-23

    Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca(2+) activity. However, whether resting astrocyte Ca(2+) can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca(2+) imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca(2+) in the soma and endfeet. The drop in intracellular Ca(2+) was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca(2+) stores and nitric oxide. The reduction in astrocyte endfoot Ca(2+) was coincident with an increase in arteriole tone, and both the Ca(2+) drop and the tone change were prevented by an NMDA receptor antagonist. Astrocyte patch-clamp experiments verified that the glutamate receptors in question were located on astrocytes and that Ca(2+) changes within astrocytes were responsible for the long-lasting change in arteriole diameter caused by theta burst neural activity. In astrocytes from animals that lived in an enriched environment, we measured a relatively lower resting Ca(2+) level that occluded any further drop in Ca(2+) in response to theta burst activity. These data suggest that electrically evoked patterns of neural activity or natural experience can adjust steady-state resting astrocyte Ca(2+) and that the effect has an impact on basal arteriole diameter.SIGNIFICANCE STATEMENT The field of astrocyte-neuron and astrocyte-arteriole interactions is currently in a state of refinement. Experimental evidence ex vivo suggests that direct manipulation of astrocyte-free Ca(2+) regulates synaptic signaling and local blood flow control; however, in vivo experiments fail to link synaptically evoked astrocyte Ca(2+) transients and immediate changes to various astrocyte-mediated processes. To clarify this discrepancy, we examined a

  11. Afferent baroreflex failure in familial dysautonomia.

    PubMed

    Norcliffe-Kaufmann, Lucy; Axelrod, Felicia; Kaufmann, Horacio

    2010-11-23

    Familial dysautonomia (FD) is due to a genetic deficiency of the protein IKAP, which affects development of peripheral neurons. Patients with FD display complex abnormalities of the baroreflex of unknown cause. To test the hypothesis that the autonomic phenotype of FD is due to selective impairment of afferent baroreceptor input, we examined the autonomic and neuroendocrine responses triggered by stimuli that either engage (postural changes) or bypass (cognitive/emotional) afferent baroreflex pathways in 50 patients with FD and compared them to those of normal subjects and to those of patients with pure autonomic failure (PAF), a disorder with selective impairment of efferent autonomic neurons. During upright tilt, in patients with FD and in patients with PAF blood pressure fell markedly but the heart rate increased in PAF and decreased in FD. Plasma norepinephrine levels failed to increase in both groups. Vasopressin levels increased appropriately in patients with PAF but failed to increase in patients with FD. Head-down tilt increased blood pressure in both groups but increased heart rate only in patients with FD. Mental stress evoked a marked increase in blood pressure and heart rate in patients with FD but little change in those with PAF. The failure to modulate sympathetic activity and to release vasopressin by baroreflex-mediated stimuli together with marked sympathetic activation during cognitive tasks indicate selective failure of baroreceptor afference. These findings indicate that IKAP is critical for the development of afferent baroreflex pathways and has therapeutic implications in the management of these patients.

  12. Nanoliposomes protect against human arteriole endothelial dysfunction induced by β-amyloid peptide

    PubMed Central

    Truran, Seth; Weissig, Volkmar; Madine, Jillian; Davies, Hannah A; Guzman-Villanueva, Diana; Franco, Daniel A; Karamanova, Nina; Burciu, Camelia; Serrano, Geidy; Beach, Thomas G

    2015-01-01

    We tested whether nanoliposomes containing phosphatidylcholine, cholesterol and phosphatidic acid (NLPA) prevent β-amyloid 1-42 (Aβ42) fibrillation and Aβ42-induced human arteriole endothelial dysfunction. NLPA abolished Aβ42 fibril formation (thioflavin-T fluorescence/electron microscopy). In ex-vivo human adipose and leptomeningeal arterioles, Aβ42 impaired dilator response to acetylcholine that was reversed by NLPA; this protection was abolished by L-NG-nitroarginine methyl ester. Aβ42 reduced human umbilical vein endothelial cell NO production that was restored by NLPA. Nanoliposomes prevented Aβ42 amyloid formation, reversed Aβ42-induced human microvascular endothelial dysfunction and may be useful in Alzheimer’s disease. PMID:26661197

  13. Differentiation of arterioles from venules in mouse histology images using machine learning.

    PubMed

    Elkerton, J Sachi; Xu, Yiwen; Pickering, J Geoffrey; Ward, Aaron D

    2017-04-01

    Analysis and morphological comparison of the arteriolar and venular components of a microvascular network are essential to our understanding of multiple diseases affecting every organ system. We have developed and evaluated the first fully automatic software system for differentiation of arterioles from venules on high-resolution digital histology images of the mouse hind limb immunostained with smooth muscle [Formula: see text]-actin. Classifiers trained on statistical and morphological features by supervised machine learning provided useful classification accuracy for differentiation of arterioles from venules, achieving an area under the receiver operating characteristic curve of 0.89. Feature selection was consistent across cross validation iterations, and a small set of two features was required to achieve the reported performance, suggesting the generalizability of the system. This system eliminates the need for laborious manual classification of the hundreds of microvessels occurring in a typical sample and paves the way for high-throughput analysis of the arteriolar and venular networks in the mouse.

  14. Reticulospinal actions on primary afferent depolarization of cutaneous and muscle afferents in the isolated frog neuraxis.

    PubMed

    González, H; Jiménez, I; Rudomin, P

    1993-01-01

    The effects of the brainstem reticular formation on the intraspinal excitability of low threshold cutaneous and muscle afferents were studied in the frog neuraxis isolated together with the right hindlimb nerves. Stimulation of low threshold fibers (less than two times threshold) in cutaneous nerves produced short latency, negative field potentials in the ipsilateral dorsal neuropil (200-400 microns depth) that reversed to positivity at deeper regions (500-700 microns). Stimulation of low threshold fibers (less than two times threshold) in muscle nerves produced, instead, negative response that acquired their maximum amplitude in the ventral neuropil (700-900 microns depth). These electrophysiological findings suggest, in agreement with observations in the cat, that low threshold cutaneous and muscle afferents end at different sites in the spinal cord. Intraspinal microstimulation applied within the dorsal neuropil produced antidromic responses in low threshold cutaneous afferents that were increased in size following stimulation of the dorsal or ventral roots, as well as of the brainstem reticular formation. This increase in excitability is interpreted as being due to primary afferent depolarization (PAD) of the intraspinal terminals of cutaneous fibers. Antidromic responses recorded in muscle nerves following intraspinal stimulation within the ventral neuropil were also increased following conditioning stimulation of adjacent dorsal or ventral roots. However, stimulation of the bulbar reticular formation produced practically no changes in the antidromic responses, but was able to inhibit the PAD of low threshold muscle afferents elicited by stimulation of the dorsal or ventral roots. It is suggested that the PAD of low threshold cutaneous and muscle afferents is mediated by independent sets of interneurons. Reticulospinal fibers would have excitatory connections with the interneurons mediating the PAD of cutaneous fibers and inhibitory connections with the

  15. Rabbit Erythrocytes Release ATP and Dilate Skeletal Muscle Arterioles in the Presence of Reduced Oxygen Tension

    PubMed Central

    Sprague, Randy S.; Hanson, Madelyn S.; Achilleus, David; Bowles, Elizabeth A.; Stephenson, Alan H.; Sridharan, Meera; Adderley, Shaquria; Ellsworth, Mary L.

    2010-01-01

    In skeletal muscle, oxygen (O2) delivery to appropriately meet metabolic need requires mechanisms for detection of the magnitude of O2 demand and the regulation of O2 delivery. Erythrocytes, when exposed to decreases in O2 tension, release both O2 and the vasodilator, adenosine triphosphate (ATP). The aims of this study were to establish that erythrocytes release ATP in response to reduced O2 tension and determine if erythrocytes are necessary for dilation of isolated skeletal muscle arterioles exposed to reduced extra-luminal O2 tension. Rabbit erythrocytes exposed to reduced O2 tension in a tonometer (n = 5, PO2 = 27 ± 3, p<0.01) released ATP in response to reduced O2 tension. ATP release increased proportional to the decrease in O2 tension. The contribution of erythrocytes to the response of skeletal muscle arterioles to reduced extra-luminal O2 tension was determined using isolated hamster cheek pouch retractor muscle arterioles perfused with buffer (n = 11, mean diameter 52 ± 3 μm) in the absence and presence of rabbit erythrocytes. Without erythrocytes, arterioles did not dilate when exposed to reduced extra-luminal O2 tension (PO2 = 32 ± 4 mm Hg). In contrast, when rabbit erythrocytes were present in the perfusate (hematocrit 15%) the same decrease in O2 tension resulted in a 20 ± 4% dilation (p<0.01). These results provide support for the hypothesis that erythrocytes, via their ability to release O2 along with ATP in response to exposure to reduced O2 tension, can participate in the matching of O2 delivery with metabolic need in skeletal muscle. PMID:19307706

  16. TRPV1 attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation in hypertension.

    PubMed

    Zhang, Ming-Jie; Liu, Yun; Hu, Zi-Cheng; Zhou, Yi; Pi, Yan; Guo, Lu; Wang, Xu; Chen, Xue; Li, Jing-Cheng; Zhang, Li-Li

    2017-04-01

    The phenotypic modulation of contractile vascular smooth muscle cell (VSMC) is widely accepted as the pivotal process in the arterial remodeling induced by hypertension. This study aimed to investigate the potential role of transient receptor potential vanilloid type 1 (TRPV1) on regulating VSMC plasticity and intracranial arteriole remodeling in hypertension. Spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats and TRPV1(-/-) mice on a C57BL/6J background were used. By microscopic observation of the histopathological sections of vessels from hypertensive SHR and age-matched normotensive WKY control rats, we found that hypertension induced arterial remodeling. Decreased α-smooth muscle actin (α-SMA) and SM22α while increased osteopontin (OPN) were observed in aorta and VSMCs derived from SHR compared with those in WKY, and VSMCs derived from SHR upregulated inflammatory factors. TRPV1 activation by capsaicin significantly increased expression of α-SMA and SM22α, reduced expression of OPN, retarded proliferative and migratory capacities and inhibited inflammatory status in VSMCs from SHR, which was counteracted by TRPV1 antagonist 5'-iodoresiniferatoxin (iRTX) combined with capsaicin. TRPV1 activation by capsaicin ameliorated intracranial arteriole remodeling in SHR and deoxycorticosterone acetate (DOCA)-salt hypertensive mice. However, the attenuation of arteriole remodeling by capsaicin was not observed in TRPV1(-/-) mice. Furthermore, TRPV1 activation significantly decreased the activity of PI3K and phosphorylation level of Akt in SHR-derived VSMCs. Taken together, we provide evidence that TRPV1 activation by capsaicin attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation during hypertension, which may be at least partly attributed to the suppression PI3K/Akt signaling pathway. These findings highlight the prospect of TRPV1 in prevention and treatment of hypertension.

  17. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    PubMed

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  18. Cross-Sectional Shape of Rat Mesenteric Arterioles at Branching Studied by Confocal Laser Microscopy

    NASA Astrophysics Data System (ADS)

    Nakano, Atushi; Minamiyama, Motomu; Niimi, Hideyuki

    This study was aimed to investigate the cross-sectional shape of mesenteric arterioles at branching, using confocal laser microscopy. Wistar rats (8 weeks, male) were anesthetized with thiobutabarbital sodium. Blood flow and microvascular network in the mesentery were observed using video microscopy. The rat intestine with mesentery was extracted and the intestinal vasculature was perfused with Krebs-Ringer and then fixed with paraformaldehyde under a static pressure of 100mmHg. A section of mesentery was isolated from the intestine, and spread up to the in vivo geometry based on the intravital microscopic observation. The mesentery section was stained with tetramethyl rhodamine isothiocyanate (TRITC)-phalloidin. The samples were observed under a confocal laser microscope. The cross-sectional image was re-sliced to measure the cross-sectional area and major/minor axes of the best fitting ellipse. The aspect ratio was defined in terms of the minor/major diameter ratio. The extended focus image of mesenteric arterioles showed that the cross-sectional shape was not circular but elliptic-like. The cross-sectional area of the parent vessel decreased from proximal to distal positions. The mean aspect ratio of the parent vessel was approximately 0.5, while that of the branching vessel was approximately 0.8. The flattened shape and variation of the cross-sectional area of arterioles requires some correction of in vivo data of the two-dimensional mesenteric microvasculature obtained using intravital microscopy.

  19. Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles.

    PubMed

    Priestley, Jessica R C; Buelow, Matthew W; McEwen, Scott T; Weinberg, Brian D; Delaney, Melanie; Balus, Sarah F; Hoeppner, Carlyn; Dondlinger, Lynn; Lombard, Julian H

    2013-09-01

    We investigated the effect of suppressing plasma angiotensin II (ANG II) levels on arteriolar relaxation in the hamster cheek pouch. Arteriolar diameters were measured via television microscopy during short-term (3-6days) high salt (HS; 4% NaCl) diet and angiotensin converting enzyme (ACE) inhibition with captopril (100mg/kg/day). ACE inhibition and/or HS diet eliminated endothelium-dependent arteriolar dilation to acetylcholine, endothelium-independent dilation to the NO donor sodium nitroprusside, the prostacyclin analogs carbacyclin and iloprost, and the KATP channel opener cromakalim; and eliminated arteriolar constriction during KATP channel blockade with glibenclamide. Scavenging of superoxide radicals and low dose ANG II infusion (25ng/kg/min, subcutaneous) reduced oxidant stress and restored arteriolar dilation in arterioles of HS-fed hamsters. Vasoconstriction to topically-applied ANG II was unaffected by HS diet while arteriolar responses to elevation of superfusion solution PO2 were unaffected (5% O2, 10% O2) or reduced (21% O2) by HS diet. These findings indicate that sustained exposure to low levels of circulating ANG II leads to widespread dysfunction in endothelium-dependent and independent vascular relaxation mechanisms in cheek pouch arterioles by increasing vascular oxidant stress, but does not potentiate O2- or ANG II-induced constriction of arterioles in the distal microcirculation of normotensive hamsters. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles

    PubMed Central

    Mishra, Anusha; Reynolds, James P.; Chen, Yang; Gourine, Alexander V.; Rusakov, Dmitri A.; Attwell, David

    2016-01-01

    Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies BOLD functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptors (mGluR5) on astrocytes, evoking Ca2+ release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knock-out of the IP3 receptors that release Ca2+ from stores does not affect neurovascular coupling. We now show that buffering astrocyte Ca2+ inhibits neuronally-evoked capillary dilation, that astrocyte [Ca2+]i is raised not by release from stores but by entry through ATP-gated channels, and that Ca2+ generates arachidonic acid via phospholipase D2 and diacylglycerol kinase rather than phospholipase A2. In contrast, dilation of arterioles depends on NMDA receptor activation and Ca2+-dependent NO generation by interneurons. These results reveal that different signalling cascades regulate cerebral blood flow at the capillary and arteriole levels. PMID:27775719

  1. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    NASA Astrophysics Data System (ADS)

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-10-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  2. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    PubMed Central

    Chesnutt, Jennifer K W; Han, Hai-Chao

    2013-01-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD), and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion, and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD, and arteriole tortuosity play important roles in platelet activation and thrombus formation. PMID:23974300

  3. Endothelin-1, but not angiotensin II, induces afferent arteriolar myosin diphosphorylation as a potential contributor to prolonged vasoconstriction.

    PubMed

    Takeya, Kosuke; Wang, Xuemei; Kathol, Iris; Loutzenhiser, Kathy; Loutzenhiser, Rodger; Walsh, Michael P

    2015-02-01

    Bolus administration of endothelin-1 elicits long-lasting renal afferent arteriolar vasoconstriction, in contrast to transient constriction induced by angiotensin II. Vasoconstriction is generally evoked by myosin regulatory light chain (LC20) phosphorylation at Ser19 by myosin light chain kinase (MLCK), which is enhanced by Rho-associated kinase (ROCK)-mediated inhibition of myosin light chain phosphatase (MLCP). LC20 can be diphosphorylated at Ser19 and Thr18, resulting in reduced rates of dephosphorylation and relaxation. Here we tested whether LC20 diphosphorylation contributes to sustained endothelin-1 but not transient angiotensin II-induced vasoconstriction. Endothelin-1 treatment of isolated arterioles elicited a concentration- and time-dependent increase in LC20 diphosphorylation at Thr18 and Ser19. Inhibition of MLCK or ROCK reduced endothelin-1-evoked LC20 mono- and diphosphorylation. Pretreatment with an ETB but not an ETA receptor antagonist abolished LC20 diphosphorylation, and an ETB receptor agonist induced LC20 diphosphorylation. In contrast, angiotensin II caused phosphorylation exclusively at Ser19. Thus, endothelin-1 and angiotensin II induce afferent arteriolar constriction via LC20 phosphorylation at Ser19 due to calcium activation of MLCK and ROCK-mediated inhibition of MLCP. Endothelin-1, but not angiotensin II, induces phosphorylation of LC20 at Thr18. This could contribute to the prolonged vasoconstrictor response to endothelin-1.

  4. Rating AAs.

    ERIC Educational Resources Information Center

    Carter, Susan J.

    2001-01-01

    Why alternative investments? In a word: performance. Many higher education endowment and foundation managers are making increasing commitments to alternative investments, or AAs, in order to obtain higher returns and broader diversification for their investment portfolios than public securities instruments can usually provide. Learn how to handle…

  5. Rating AAs.

    ERIC Educational Resources Information Center

    Carter, Susan J.

    2001-01-01

    Why alternative investments? In a word: performance. Many higher education endowment and foundation managers are making increasing commitments to alternative investments, or AAs, in order to obtain higher returns and broader diversification for their investment portfolios than public securities instruments can usually provide. Learn how to handle…

  6. The α1B-adrenoceptor subtype mediates adrenergic vasoconstriction in mouse retinal arterioles with damaged endothelium

    PubMed Central

    Böhmer, Tobias; Manicam, Caroline; Steege, Andreas; Michel, Martin C; Pfeiffer, Norbert; Gericke, Adrian

    2014-01-01

    BACKGROUND AND PURPOSE The α1-adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to determine the contribution of individual α1-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes (α1A-AR−/−, α1B-AR−/− and α1D-AR−/− respectively). EXPERIMENTAL APPROACH Using real-time PCR, mRNA expression for individual α1-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three α1-adrenoceptor subtypes for mediating vascular responses, retinal vascular preparations from wild-type mice and mice deficient in individual α1-adrenoceptor subtypes were studied in vitro using video microscopy. KEY RESULTS Retinal arterioles expressed mRNA for all three α1-adrenoceptor subtypes. In functional studies, arterioles from wild-type mice with intact endothelium responded only negligibly to the α1-adrenoceptor agonist phenylephrine. In endothelium-damaged arterioles from wild-type mice, phenylephrine evoked concentration-dependent constriction that was attenuated by the α1-adrenoceptor blocker prazosin. Strikingly, phenylephrine only minimally constricted endothelium-damaged retinal arterioles from α1B-AR−/− mice, whereas arterioles from α1A-AR−/− and α1D-AR−/− mice constricted similarly to arterioles from wild-type mice. Constriction to U46619 was similar in endothelium-damaged retinal arterioles from all four mouse genotypes. CONCLUSIONS AND IMPLICATIONS The present study is the first to demonstrate that α1-adrenoceptor-mediated vasoconstriction in murine retinal arterioles is buffered by the endothelium. When the endothelium is damaged, a vasoconstricting role of the α1B-adrenoceptor subtype is unveiled. Hence, the α1B-adrenoceptor may represent a target to selectively modulate retinal blood flow

  7. Development, plasticity and modulation of visceral afferents

    PubMed Central

    Christianson, Julie A.; Bielefeldt, Klaus; Altier, Christophe; Cenac, Nicolas; Davis, Brian M.; Gebhart, Gerald F.; High, Karin W.; Kollarik, Marian; Randich, Alan; Undem, Brad; Vergnolle, Nathalie

    2010-01-01

    Visceral pain is the most common reason for doctor visits in the US. Like somatic pain, virtually all visceral pain sensations begin with the activation of primary sensory neurons innervating the viscera and/or the blood vessels associated with these structures. Visceral afferents also play a central role in tissue homeostasis. Recent studies show that in addition to monitoring the state of the viscera, they perform efferent functions through the release of small molecules (e.g. peptides like CGRP) that can drive inflammation, thereby contributing to the development of visceral pathologies (e.g. diabetes Razavi, R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan, X., Yantha, J., Tsui, H., Tang, L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch, H.M., 2006. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes, Cell 127 1123–1135). Visceral afferents are heterogeneous with respect to their anatomy, neurochemistry and function. They are also highly plastic in that their cellular environment continuously influences their response properties. This plasticity makes them susceptible to long-term changes that may contribute significantly to the development of persistent pain states such as those associated with irritable bowel syndrome, pancreatitis, and visceral cancers. This review examines recent insights into visceral afferent anatomy and neurochemistry and how neonatal insults can affect the function of these neurons in the adult. New approaches to the treatment of visceral pain, which focus on primary afferents, will also be discussed. PMID:19150371

  8. Afferent baroreflex failure in familial dysautonomia

    PubMed Central

    Norcliffe-Kaufmann, Lucy; Axelrod, Felicia; Kaufmann, Horacio

    2010-01-01

    Background: Familial dysautonomia (FD) is due to a genetic deficiency of the protein IKAP, which affects development of peripheral neurons. Patients with FD display complex abnormalities of the baroreflex of unknown cause. Methods: To test the hypothesis that the autonomic phenotype of FD is due to selective impairment of afferent baroreceptor input, we examined the autonomic and neuroendocrine responses triggered by stimuli that either engage (postural changes) or bypass (cognitive/emotional) afferent baroreflex pathways in 50 patients with FD and compared them to those of normal subjects and to those of patients with pure autonomic failure (PAF), a disorder with selective impairment of efferent autonomic neurons. Results: During upright tilt, in patients with FD and in patients with PAF blood pressure fell markedly but the heart rate increased in PAF and decreased in FD. Plasma norepinephrine levels failed to increase in both groups. Vasopressin levels increased appropriately in patients with PAF but failed to increase in patients with FD. Head-down tilt increased blood pressure in both groups but increased heart rate only in patients with FD. Mental stress evoked a marked increase in blood pressure and heart rate in patients with FD but little change in those with PAF. Conclusion: The failure to modulate sympathetic activity and to release vasopressin by baroreflex-mediated stimuli together with marked sympathetic activation during cognitive tasks indicate selective failure of baroreceptor afference. These findings indicate that IKAP is critical for the development of afferent baroreflex pathways and has therapeutic implications in the management of these patients. GLOSSARY FD = familial dysautonomia; FVR = forearm vascular resistance; PAF = pure autonomic failure. PMID:21098405

  9. Vagal expiratory afferent discharges during spontaneous breathing.

    PubMed

    Wei, J Y; Shen, E

    1985-06-03

    Expiratory discharges in cervical afferent vagal fibres during spontaneous respiration were observed in anesthetized animals (17 rabbits, 4 cats and 2 monkeys). The percentages of such units among the total observed fibres was 11% in rabbits, 5% in monkeys, 2% in cats. All the experiments were done after section of the recurrent laryngeal nerve and the abdominal branches of the vagus nerve. Changing the intraesophageal pressure from +15 mm Hg to -25 mm Hg by injection or suction of air into or out of the esophagus, of which the abdominal end had been ligated, did not affect the expiratory discharges significantly suggesting that the receptors were not in the esophagus. Injection of air into the lungs to elevate the intratracheal pressure to 5 mm, 10 mm or 15 mm Hg could not excite such receptors. Collapse of the lungs caused by artificial pneumothorax produced continuous discharges in such fibres. Inflation of collapsed lungs by an artificial respiration pump stopped the sustained discharges immediately. The average conduction velocity of the afferent fibres was 25.5 m/s. It seems that this is a type of slowly adapting, low threshold pulmonary receptor with medium sized afferent fibres. The adequate stimulus of such receptors is deflation of the lungs. The possible advantage of participation of such receptors, in addition to the pulmonary stretch (inflation) receptors, in regulation of normal respiration is discussed in the light of the concept of 'paired receptors'.

  10. Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles.

    PubMed

    Kang, Lori S; Chen, Bei; Reyes, Rafael A; Leblanc, Amanda J; Teng, Bunyen; Mustafa, S Jamal; Muller-Delp, Judy M

    2011-06-01

    Endothelium-dependent, nitric oxide (NO)-mediated vasodilation can be impaired by reactive oxygen species (ROS), and this deleterious effect of ROS on NO availability may increase with aging. Endothelial function declines rapidly after menopause, possibly because of loss of circulating estrogen and its antioxidant effects. The purpose of the current study was to determine the role of O(2)(-) and H(2)O(2) in regulating flow-induced dilation in coronary arterioles of young (6-mo) and aged (24-mo) intact, ovariectomized (OVX), or OVX + estrogen-treated (OVE) female Fischer 344 rats. Both aging and OVX reduced flow-induced NO production, whereas flow-induced H(2)O(2) production was not altered by age or estrogen status. Flow-induced vasodilation was evaluated before and after treatment with the superoxide dismutase (SOD) mimetic Tempol (100 μM) or the H(2)O(2) scavenger catalase (100 U/ml). Removal of H(2)O(2) with catalase reduced flow-induced dilation in all groups, whereas Tempol diminished vasodilation in intact and OVE, but not OVX, rats. Immunoblot analysis revealed elevated nitrotyrosine with aging and OVX. In young rats, OVX reduced SOD protein while OVE increased SOD in aged rats; catalase protein did not differ in any group. Collectively, these studies suggest that O(2)(-) and H(2)O(2) are critical components of flow-induced vasodilation in coronary arterioles from female rats; however, a chronic deficiency of O(2)(-) buffering by SOD contributes to impaired flow-induced dilation with aging and loss of estrogen. Furthermore, these data indicate that estrogen replacement restores O(2)(-) homeostasis and flow-induced dilation of coronary arterioles, even at an advanced age.

  11. Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity.

    PubMed

    Holmes, William R; Huwe, Janice A; Williams, Barbara; Rowe, Michael H; Peterson, Ellengene H

    2017-05-01

    Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents.NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed computational

  12. Modulation of long-latency afferent inhibition by the amplitude of sensory afferent volley.

    PubMed

    Turco, Claudia V; El-Sayes, Jenin; Fassett, Hunter J; Chen, Robert; Nelson, Aimee J

    2017-07-01

    Long-latency afferent inhibition (LAI) is the inhibition of the transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) by the sensory afferent volley following electrical stimulation of a peripheral nerve. It is unknown how the activation of sensory afferent fibers relates to the magnitude of LAI. This study investigated the relationship between LAI and the sensory nerve action potentials (SNAP) from the median nerve (MN) and the digital nerves (DN) of the second digit. LAI was obtained by delivering nerve stimulation 200 ms before a TMS pulse delivered over the motor cortex. Experiment 1 assessed the magnitude of LAI following stimulation of the contralateral MN or DN using nerve stimulus intensities relative to the maximum SNAP (SNAPmax) of that nerve and two TMS intensities (0.5- and 1-mV MEP). Results indicate that MN LAI is maximal at ~50% SNAPmax, when presumably all sensory afferents are recruited for TMS of 0.5-mV MEP. For DN, LAI appears at ~50% SNAPmax and does not increase with further recruitment of sensory afferents. Experiment 2 investigated the magnitude of LAI following ipsilateral nerve stimulation at intensities relative to SNAPmax Results show minimal LAI evoked by ipsilateral MN and no LAI following ipsilateral DN stimulation. Implications for future studies investigating LAI include adjusting nerve stimulation to 50% SNAPmax to obtain maximal LAI. Additionally, MN LAI can be used as a marker for neurological disease or injury by using a nerve stimulation intensity that can evoke a depth of LAI capable of increasing or decreasing.NEW & NOTEWORTHY This is the first investigation of the relationship between long-latency afferent inhibition (LAI) and the sensory afferent volley. Differences exist between median and digital nerve LAI. For the median nerve, LAI increases until all sensory fibers are presumably recruited. In contrast, digital nerve LAI does not increase with the recruitment of additional sensory fibers but rather is

  13. Extracellular and intracellular alkalinization and the constriction of rat cerebral arterioles.

    PubMed Central

    Apkon, M; Boron, W F

    1995-01-01

    1. Direct observations of perfused cerebral arterioles in vivo and in vitro have demonstrated that alkalinization of blood or cerebrospinal fluid (CSF) causes arteriolar constriction. Inasmuch as such alkalinizations lead to increases in intracellular pH (pHi) as well as interstitial pH (pHo), it is possible that increases in either pHi or pHo (or both) underlie alkalinization-induced cerebral vasoconstriction. In order to test the hypothesis that changes in pHi alone underline alkalinization-induced cerebral vasoconstriction, we simultaneously measured vessel diameter and pHi (using the pH-sensitive dye, SNAFL) in isolated cerebral arterioles from adult rats during imposed alterations in pHo and pHi. 2. Penetrating cerebral arterioles from the distribution of the middle cerebral artery were hand dissected, cannulated on one end and occluded distally. Vessels were inflated hydrostatically to 60 cmH2O under no-flow conditions. Confocal microscopy verified specific pH-sensitivity dye staining of the vascular smooth muscle cells within the vessel wall. 3. Extracellular alkalinization from pH 7.3 to 7.8 caused pHi to increase by 0.06 +/- 0.01 of a pH unit, and vessel diameter to decrease by 21.8 +/- 1.8% (mean +/- S.E.M.). 4. Intracellular alkalinization at constant pHo was produced by exposure to weak bases, including NH3 and trimethylamine, or by exposure to, followed by withdrawal of, weak acids, including CO2 and acetic acid. None of these treatments evoked vasoconstriction even though each of them caused increases in pHi greater than those observed in the same vessels during exposure to the pHo 7.8 solution. 5. We conclude that, at least in cerebral arterioles, alkalinization-induced vasoconstriction is mediated by an increase in pHo, not pHi [corrected]. Images Figure 2 PMID:7623289

  14. Diverse Kir Expression Contributes to Distinct Bimodal Distribution of Resting Potentials and Vasotone Responses of Arterioles

    PubMed Central

    Yang, Yuqin; Chen, Fangyi; Karasawa, Takatoshi; Ma, Ke-Tao; Guan, Bing-Cai; Shi, Xiao-Rui; Li, Hongzhe; Steyger, Peter S.; Nuttall, Alfred L.; Jiang, Zhi-Gen

    2015-01-01

    The resting membrane potential (RP) of vascular smooth muscle cells (VSMCs) is a major determinant of cytosolic calcium concentration and vascular tone. The heterogeneity of RPs and its underlying mechanism among different vascular beds remain poorly understood. We compared the RPs and vasomotion properties between the guinea pig spiral modiolar artery (SMA), brain arterioles (BA) and mesenteric arteries (MA). We found: 1) RPs showed a robust bimodal distribution peaked at -76 and -40 mV evenly in the SMA, unevenly at -77 and -51 mV in the BA and ~-71 and -52 mV in the MA. Ba2+ 0.1 mM eliminated their high RP peaks ~-75 mV. 2) Cells with low RP (~-45 mV) hyperpolarized in response to 10 mM extracellular K+, while cells with a high RP depolarized, and cells with intermediate RP (~-58 mV) displayed an initial hyperpolarization followed by prolonged depolarization. Moderate high K+ typically induced dilation, constriction and a dilation followed by constriction in the SMA, MA and BA, respectively. 3) Boltzmann-fit analysis of the Ba2+-sensitive inward rectifier K+ (Kir) whole-cell current showed that the maximum Kir conductance density significantly differed among the vessels, and the half-activation voltage was significantly more negative in the MA. 4) Corresponding to the whole-cell data, computational modeling simulated the three RP distribution patterns and the dynamics of RP changes obtained experimentally, including the regenerative swift shifts between the two RP levels after reaching a threshold. 5) Molecular works revealed strong Kir2.1 and Kir2.2 transcripts and Kir2.1 immunolabeling in all 3 vessels, while Kir2.3 and Kir2.4 transcript levels varied. We conclude that a dense expression of functional Kir2.X channels underlies the more negative RPs in endothelial cells and a subset of VSMC in these arterioles, and the heterogeneous Kir function is primarily responsible for the distinct bimodal RPs among these arterioles. The fast Kir-based regenerative shifts

  15. Effect of Hyperglycemia on Brain Penetrating Arterioles and Cerebral Blood Flow Before and After Ischemia/Reperfusion

    PubMed Central

    Godfrey, Julie A.

    2010-01-01

    The effect of preexisiting hyperglycemia on cerebral blood flow (CBF) and brain penetrating arterioles before and after 2 h of ischemia and 30 min of reperfusion was determined. Male Wistar rats that were either hyperglycemic (50 mg/kg streptozotocin; n=24) or normoglycemic (n=24) were subjected to transient ischemia by filament occlusion or nonischemic. CBF was measured prior to ischemia using microspheres and during transient ischemia using laser Doppler. Edema was compared by wet/dry weights. Constriction to apamin, TRAM-34, and L-NNA, inhibitors of small- and intermediate-conductance calcium-activated potassium channels (SK and IK) and nitric oxide, were compared in penetrating arterioles from the ischemic hemisphere to investigate changes in basal tone and endothelium-dependent vasodilator responses. Preexisiting hyperglycemia did not affect CBF in non-ischemic animals or after transient ischemia; however, edema was significantly greater. Ischemia and reperfusion caused decreased basal tone in penetrating arterioles similarly in normoglycemic and hyperglycemic animals that was restored by apamin, and further increased by TRAM-34 and L-NNA. The restoration of tone in penetrating arterioles by apamin and TRAM-34 suggests that transient ischemia activates SK and IK channels in penetrating arterioles. This effect of ischemia was not different between normoglycemic and hyperglycemic animals, suggesting that it was related to ischemia and reperfusion rather than hyperglycemia. PMID:20563316

  16. Effect of hyperglycemia on brain penetrating arterioles and cerebral blood flow before and after ischemia/reperfusion.

    PubMed

    Cipolla, Marilyn J; Godfrey, Julie A

    2010-06-01

    The effect of preexisiting hyperglycemia on cerebral blood flow (CBF) and brain penetrating arterioles before and after 2 h of ischemia and 30 min of reperfusion was determined. Male Wistar rats that were either hyperglycemic (50 mg/kg streptozotocin; n=24) or normoglycemic (n=24) were subjected to transient ischemia by filament occlusion or nonischemic. CBF was measured prior to ischemia using microspheres and during transient ischemia using laser Doppler. Edema was compared by wet/dry weights. Constriction to apamin, TRAM-34, and L-NNA, inhibitors of small- and intermediate-conductance calcium-activated potassium channels (SK and IK) and nitric oxide, were compared in penetrating arterioles from the ischemic hemisphere to investigate changes in basal tone and endothelium-dependent vasodilator responses. Preexisiting hyperglycemia did not affect CBF in non-ischemic animals or after transient ischemia; however, edema was significantly greater. Ischemia and reperfusion caused decreased basal tone in penetrating arterioles similarly in normoglycemic and hyperglycemic animals that was restored by apamin, and further increased by TRAM-34 and L-NNA. The restoration of tone in penetrating arterioles by apamin and TRAM-34 suggests that transient ischemia activates SK and IK channels in penetrating arterioles. This effect of ischemia was not different between normoglycemic and hyperglycemic animals, suggesting that it was related to ischemia and reperfusion rather than hyperglycemia.

  17. Role of capillary pericytes and precapillary arterioles in the vascular mechanism of betahistine in a guinea pig inner ear model.

    PubMed

    Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Strupp, Michael; Jakob, Mark; Canis, Martin

    2017-08-14

    Betahistine is a histamine analogue that is used for the treatment of Menière's disease. Animal studies showed that it increases local blood flow in the stria vascularis. In terms of its mode of action, recent studies have prompted discussion of whether betahistine actively affects cochlear microcirculation by dilations of pericytes or of precapillary arterioles or by mere downstream effects. Hence, we investigated the effects of betahistine on cochlear capillary pericytes and precapillary arterioles. The stria vascularis was visualized in 12 guinea pigs by in vivo fluorescence microscopy. In these, 152 pericytes were stained and local diameter at sites of pericyte somas and downstream controls as well as intravascular blood flow were measured before and after betahistine application. Moreover, in two guinea pigs the precapillary arterioles were visualized by 2-photon-microscopy before and after betahistine application. There was no significant change in capillary diameter at sites of pericyte somas after betahistine application compared to controls, baseline or downstream controls, even though cochlear blood flow increased significantly. The two-photon measurements indicated an active dilation of precapillary arterioles. Since we found no evidence that betahistine affects cochlear microcirculation by cochlear pericytes, its main mode of action is evidently active dilation of pre-capillary arterioles. These findings are in line with similar effects reported in the central nervous system and indicate an active effect on cochlear microcirculation. Copyright © 2017. Published by Elsevier Inc.

  18. Afferent innervation patterns of the saccule in pigeons

    NASA Technical Reports Server (NTRS)

    Zakir, M.; Huss, D.; Dickman, J. D.

    2003-01-01

    The innervation patterns of vestibular saccular afferents were quantitatively investigated in pigeons using biotinylated dextran amine as a neural tracer and three-dimensional computer reconstruction. Type I hair cells were found throughout a large portion of the macula, with the highest density observed in the striola. Type II hair cells were located throughout the macula, with the highest density in the extrastriola. Three classes of afferent innervation patterns were observed, including calyx, dimorph, and bouton units, with 137 afferents being anatomically reconstructed and used for quantitative comparisons. Calyx afferents were located primarily in the striola, innervated a number of type I hair cells, and had small innervation areas. Most calyx afferent terminal fields were oriented parallel to the anterior-posterior axis and the morphological polarization reversal line. Dimorph afferents were located throughout the macula, contained fewer type I hair cells in a calyceal terminal than calyx afferents and had medium sized innervation areas. Bouton afferents were restricted to the extrastriola, with multi-branching fibers and large innervation areas. Most of the dimorph and bouton afferents had innervation fields that were oriented dorso-ventrally but were parallel to the neighboring reversal line. The organizational morphology of the saccule was found to be distinctly different from that of the avian utricle or lagena otolith organs and appears to represent a receptor organ undergoing evolutionary adaptation toward sensing linear motion in terrestrial and aerial species.

  19. Hair-Cell Versus Afferent Adaptation in the Semicircular Canals

    PubMed Central

    Rabbitt, R. D.; Boyle, R.; Holstein, G. R.; Highstein, S. M.

    2010-01-01

    The time course and extent of adaptation in semicircular canal hair cells was compared to adaptation in primary afferent neurons for physiological stimuli in vivo to study the origins of the neural code transmitted to the brain. The oyster toadfish, Opsanus tau, was used as the experimental model. Afferent firing-rate adaptation followed a double-exponential time course in response to step cupula displacements. The dominant adaptation time constant varied considerably among afferent fibers and spanned six orders of magnitude for the population (~1 ms to >1,000 s). For sinusoidal stimuli (0.1–20 Hz), the rapidly adapting afferents exhibited a 90° phase lead and frequency-dependent gain, whereas slowly adapting afferents exhibited a flat gain and no phase lead. Hair-cell voltage and current modulations were similar to the slowly adapting afferents and exhibited a relatively flat gain with very little phase lead over the physiological bandwidth and dynamic range tested. Semicircular canal microphonics also showed responses consistent with the slowly adapting subset of afferents and with hair cells. The relatively broad diversity of afferent adaptation time constants and frequency-dependent discharge modulations relative to hair-cell voltage implicate a subsequent site of adaptation that plays a major role in further shaping the temporal characteristics of semicircular canal afferent neural signals. PMID:15306633

  20. Changes in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy.

    PubMed

    Smith, Samantha D; Choudhury, Ruhul H; Matos, Patricia; Horn, James A; Lye, Stephen J; Dunk, Caroline E; Aplin, John D; Jones, Rebecca L; Harris, Lynda K

    2016-05-01

    Uterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placental-derived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy.

  1. Differentiation of arterioles from venules in mouse histology images using machine learning

    NASA Astrophysics Data System (ADS)

    Elkerton, J. S.; Xu, Yiwen; Pickering, J. G.; Ward, Aaron D.

    2016-03-01

    Analysis and morphological comparison of arteriolar and venular networks are essential to our understanding of multiple diseases affecting every organ system. We have developed and evaluated the first fully automatic software system for differentiation of arterioles from venules on high-resolution digital histology images of the mouse hind limb immunostained for smooth muscle α-actin. Classifiers trained on texture and morphologic features by supervised machine learning provided excellent classification accuracy for differentiation of arterioles and venules, achieving an area under the receiver operating characteristic curve of 0.90 and balanced false-positive and false-negative rates. Feature selection was consistent across cross-validation iterations, and a small set of three features was required to achieve the reported performance, suggesting potential generalizability of the system. This system eliminates the need for laborious manual classification of the hundreds of microvessels occurring in a typical sample, and paves the way for high-throughput analysis the arteriolar and venular networks in the mouse.

  2. Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 microm.

    PubMed

    Versluis, J P; Heslinga, J W; Sipkema, P; Westerhof, N

    2001-11-01

    Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (P(int)). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, P(int) were calculated with nonlinear regression. The P(int) at the level of the septal artery (diameter, 150-250 microm) was 23.2 +/- 4.4 cmH2O (n = 12). In arterioles with a diameter range between 24 and 110 microm, P(int) was 1.7 +/- 0.5 cmH2O (n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, P(int) was 1.1 +/- 1.1 cmH2O (n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 microm. The second waterfall is probably located in the small postcapillary venules.

  3. Permeabilities of single arterioles and venules in the frog skin: a functional and morphological study.

    PubMed

    Olesen, S P; de Saint-Aubain, M L; Bundgaard, M

    1984-07-01

    The permeability of single subcutaneous microvessels in the frog skin was determined with electrophysiological techniques after only minimal surgical intervention. The organization of blood vessels in the frog skin is described at the microscopic level. Transmission electron microscopy showed that the subcutaneous microvessels belong to the class of "continuous" vessels (H. Bennett, J. Luft, and J. Hampton, 1959, Amer. J. Physiol. 196, 381-390). Capillaries in the true sense of the word are rare in this subcutaneous tissue. The electrical resistance of the endothelium in well defined segments of the subcutaneous microvessels was determined by means of current injection and voltage recording microelectrodes using cable theory for the analysis. The average resistances were 70 and 24 omega.cm2 for arterioles and venules, respectively; the mean values of the two groups were significantly different (P less than 0.001). These figures are close to those obtained on microvessels in skeletal muscle (S.-P. Olesen and C. Crone, 1983, Biophys. J. 42, 31-41), but are about one order of magnitude higher than resistances of mesenteric microvessels. The calculated sodium permeabilities were for arterioles: PNa+ = 1.6 x 10(-5) cm sec(-1) and for venules: 4.6 x 10(-5) cm sec(-1).

  4. Localized arteriole formation directly adjacent to the site of VEGF-induced angiogenesis in muscle.

    PubMed

    Springer, Matthew L; Ozawa, Clare R; Banfi, Andrea; Kraft, Peggy E; Ip, Tze-Kin; Brazelton, Timothy R; Blau, Helen M

    2003-04-01

    We have shown previously that implantation of myoblasts constitutively expressing the VEGF-A gene into nonischemic mouse skeletal muscle leads to overgrowth of capillary-like blood vessels and hemangioma formation. These aberrant effects occurred directly at the implantation site. We show here that these regions result from angiogenic capillary growth and involve a change in capillary growth pattern and that smooth muscle-coated vessels similar to arterioles form directly adjacent to the implantation site. Myoblasts genetically engineered to produce VEGF were implanted into mouse leg muscles. Implantation sites were surrounded by a zone of dense capillary-sized vessels, around which was a second zone of muscle containing larger, smooth-muscle-covered vessels but few capillaries, and an outer zone of muscle exhibiting normal capillary density. The lack of capillaries in the middle region suggests that the preexisting capillaries adjacent to the implantation site underwent enlargement and/or fusion and recruited a smooth muscle coat. Capillaries at the implantation site were frequently wrapped around VEGF-producing muscle fibers and were continuous with the circulation and were not observed to include bone-marrow-derived endothelial cells. In contrast with the distant arteriogenesis resulting from VEGF delivery described in previous studies, we report here that highly localized arterioles also form adjacent to the site of delivery.

  5. Cyclooxygenase 2 contributes to bradykinin-induced microvascular responses in peripheral arterioles after cardiopulmonary bypass.

    PubMed

    Feng, Jun; Anderson, Kelsey; Liu, Yuhong; Singh, Arun K; Ehsan, Afshin; Sellke, Frank W

    2017-10-01

    Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 μm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10(-10) to 10(-6)M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10(-5)M). The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05). Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Acute Retinal Ischemia Inhibits Endothelium-Dependent Nitric Oxide–Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production

    PubMed Central

    Ren, Yi; Potts, Luke B.; Yuan, Zhaoxu; Kuo, Enoch; Rosa, Robert H.; Kuo, Lih

    2012-01-01

    Purpose. Because retinal vascular disease is associated with ischemia and increased oxidative stress, the vasodilator function of retinal arterioles was examined after retinal ischemia induced by elevated intraocular pressure (IOP). The role of superoxide anions in the development of vascular dysfunction was assessed. Methods. IOP was increased and maintained at 80 to 90 mm Hg for 30, 60, or 90 minutes by infusing saline into the anterior chamber of a porcine eye. The fellow eye with normal IOP (10–20 mm Hg) served as control. In some pigs, superoxide dismutase mimetic TEMPOL (1 mM) or vehicle (saline) was injected intravitreally before IOP elevation. After enucleation, retinal arterioles were isolated and pressurized without flow for functional analysis by recording diameter changes using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production in isolated retinal arterioles. Results. Isolated retinal arterioles developed stable basal tone and the vasodilations to endothelium-dependent nitric oxide (NO)-mediated agonists bradykinin and L-lactate were significantly reduced only by 90 minutes of ischemia. However, vasodilation to endothelium-independent NO donor sodium nitroprusside was unaffected after all time periods of ischemia. DHE staining showed that 90 minutes of ischemia significantly increased superoxide levels in retinal arterioles. Intravitreal injection of membrane-permeable radical scavenger but not vehicle before ischemia prevented elevation of vascular superoxide and preserved bradykinin-induced dilation. Conclusions. Endothelium-dependent NO-mediated dilation of retinal arterioles is impaired by 90 minutes of ischemia induced by elevated IOP. The inhibitory effect appears to be mediated by the alteration of NO signaling via vascular superoxide. PMID:22110081

  7. Relationship of wall-to-lumen ratio of retinal arterioles with clinic and 24-hour blood pressure.

    PubMed

    Salvetti, Massimo; Agabiti Rosei, Claudia; Paini, Anna; Aggiusti, Carlo; Cancarini, Anna; Duse, Sarah; Semeraro, Francesco; Rizzoni, Damiano; Agabiti Rosei, Enrico; Muiesan, Maria Lorenza

    2014-05-01

    Wall-to-lumen ratio of retinal arterioles might serve as an in vivo parameter of vascular damage. We analyzed the impact of brachial clinic blood pressure (BP), of central BP, and of 24-hour BP on wall-to-lumen ratio (WLR) of retinal arterioles. In 295 subjects (147 men; age range, 22-72 years; mean age, 54±7 years), WLR of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. In addition, clinic and 24-hour BP values were measured. Central hemodynamics was assessed by pulse wave analysis. In treated patients with essential hypertension (n=100), a higher WLR (0.29±0.18 versus 0.23±0.13; P=0.009) was observed in comparison with normotensive individuals (n=119); no significant differences were observed between treated and untreated hypertensive patients (0.29±0.18 versus 0.28±0.18; P=0.7). WLR of retinal arterioles was significantly related to clinic systolic (r=0.18; P=0.002) and pulse pressure (r=0.20; P=0.001), to 24-hour systolic (r=0.25; P=0.0001) and pulse pressure (r=0.17; P=0.005), and to central systolic (r=0.16; P=0.006) and pulse pressure (r=0.18; P=0.002). Multiple regression analysis revealed that only mean systolic 24-hour BP was independently associated with an increased WLR of retinal arterioles. In this large group of hypertensive patients and normotensive individuals, 24-hour systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.

  8. Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles.

    PubMed

    Umesalma, Shaikamjad; Houwen, Frederick Keith; Baumbach, Gary L; Chan, Siu-Lung

    2016-03-01

    Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1-induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy. © 2016 American Heart Association, Inc.

  9. Extraocular muscle afferent signals modulate visual attention.

    PubMed

    Balslev, Daniela; Newman, William; Knox, Paul C

    2012-10-09

    Extraocular muscle afferent signals contribute to oculomotor control and visual localization. Prompted by the close links between the oculomotor and attention systems, it was investigated whether these proprioceptive signals also modulated the allocation of attention in space. A suction sclera contact lens was used to impose an eye rotation on the nonviewing, dominant eye. With their viewing, nondominant eye, participants (n = 4) fixated centrally and detected targets presented at 5° in the left or right visual hemifield. The position of the viewing eye was monitored throughout the experiment. As a control, visual localization was tested using finger pointing without visual feedback of the hand, whereas the nonviewing eye remained deviated. The sustained passive rotation of the occluded, dominant eye, while the other eye maintained central fixation, resulted in a lateralized change in the detectability of visual targets. In all participants, the advantage in speed and accuracy for detecting right versus left hemifield targets that occurred during a sustained rightward eye rotation of the dominant eye was reduced or reversed by a leftward eye rotation. The control experiment confirmed that the eye deviation procedure caused pointing errors consistent with an approximately 2° shift in perceived eye position, in the direction of rotation of the nonviewing eye. With the caveat of the small number of participants, these results suggest that extraocular muscle afferent signals modulate the deployment of attention in visual space.

  10. Afferent Nerve Regulation of Bladder Function in Health and Disease

    PubMed Central

    de Groat, William C.; Yoshimura, Naoki

    2012-01-01

    The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

  11. Rapid dilation of arterioles with single contraction of hamster skeletal muscle.

    PubMed

    VanTeeffelen, Jurgen W G E; Segal, Steven S

    2006-01-01

    Skeletal muscle blood flow increases rapidly with exercise onset, but little is known of where or how the rapid onset of vasodilation (ROV) is governed within the microcirculation. In the retractor muscle of anesthetized hamsters (n = 26), we tested the following: 1) where in the resistance network ROV occurred, 2) how microvascular responses were affected by the duration of contraction, and 3) whether ROV involved muscarinic receptor activation. Single tetanic contractions were evoked using supramaximal field stimulation (100 Hz) to depolarize motor end plates. In response to a 200-ms contraction, red blood cell (rbc) velocity (V(rbc)) in feed arteries (FA; rest: 17.8 +/- 2 mm/s) increased within 1 s; a transient first peak (P1; 50 +/- 7% increase) occurred at approximately 5 s; and a second peak (P2; 50 +/- 15% increase) occurred at approximately 15-20 s. For vasodilation, P1 increased in frequency from proximal FA (2/7) and 1A arterioles (2/7) to distal 2A (4/7) and 3A (7/8) arterioles (P < 0.05). Relative to resting (and maximal, 10 microM sodium nitroprusside) diameters, P1 increased from proximal (FA, 3 +/- 2% from 57 +/- 5 microm) to distal (3A, 27 +/- 6% from 14 +/- 1 microm) vessel branches (P < 0.05). P2 was manifest in all vessels and increased relative to resting diameters from FA (11 +/- 3%) to 3A (36 +/- 6%) branches (P < 0.01). Extending a contraction from 200 to 1,000 ms (tension x time integral from 17 +/- 2 to 73 +/- 4 mN/mm2 x s) increased P1 and P2 for V(rbc) and for diameter (P < 0.05) while reducing the time of onset for P2 (P < 0.05). Superfusion with atropine (10 microM) attenuated P1 of vasodilation (200 ms contraction) from 26 +/- 8% to 6 +/- 2% (n = 7 across branches; P < 0.05) and reduced the diameter x time integral by 46 +/- 13% (P < 0.05) without changing P2. We conclude that ROV in the hamster retractor muscle is initiated in distal arterioles, increases with the duration of muscle contraction, and involves muscarinic receptor

  12. Pharmacological evidence for capacitative Ca(2+) entry in cannulated and pressurized skeletal muscle arterioles.

    PubMed

    Potocnik, S J; Hill, M A

    2001-09-01

    Arteriolar myogenic tone shows a marked dependency on extracellular Ca(2+). The contribution played by mechanisms such as intracellular Ca(2+) release and capacitative entry, however, are less certain. The present studies aimed to demonstrate functional evidence for involvement of such mechanisms in myogenic tone and reactivity. Single cremaster arterioles were denuded of endothelium, pressurized under no-flow conditions and loaded with fura 2-AM for measurement of changes in intracellular Ca(2+) [Ca(2+)](i). The cell permeable, putative, IP(3) receptor antagonist 2APB (2 aminoethoxydiphenyl borate) was used to determine the possible role of IP(3) receptor-mediated mechanisms in arteriolar myogenic tone and reactivity. Arterioles dilated in response to increasing concentrations of 2APB (1 - 300 microM) without a concomitant change in global [Ca(2+)](i). Also 2APB (50 microM) completely inhibited the myogenic constriction in response to a step change in luminal pressure (50 - 120 mmHg) with no apparent effect on pressure-mediated increases in [Ca(2+)](i). 2APB markedly attenuated the constrictor response and [Ca(2+)](i) increase stimulated by phenylephrine but not KCl. Capacitative Ca(2+) influx in arterioles was demonstrated either by re-addition of extracellular [Ca(2+)] following pre-treatment with 1 or 10 microM nifedipine in Ca(2+) free buffer or exposure of vessels to thapsigargin (1 microM) to induce store depletion. In both cases 2APB inhibited the increase in [Ca(2+)](i). Capacitative Ca(2+) entry showed an inverse relationship with intraluminal pressure over the range 10 - 120 mmHg. Consistent with an effect on a Ca(2+) entry pathway, 2APB had no effect on intracellular (caffeine releasable) Ca(2+) stores while decreasing the rate of Mn(2+) quench of fura 2 fluorescence. The results provide functional evidence for capacitative Ca(2+) entry in intact arteriolar smooth muscle. The effectiveness of 2APB in inhibiting both non-voltage gated Ca(2+) entry and

  13. Dynamin-related protein 1 mediates low glucose-induced endothelial dysfunction in human arterioles.

    PubMed

    Tanner, Michael J; Wang, Jingli; Ying, Rong; Suboc, Tisha B; Malik, Mobin; Couillard, Allison; Branum, Amberly; Puppala, Venkata; Widlansky, Michael E

    2017-03-01

    Intensive glycemic regulation has resulted in an increased incidence of hypoglycemia. Hypoglycemic burden correlates with adverse cardiovascular complications and contributes acutely and chronically to endothelial dysfunction. Prior data indicate that mitochondrial dysfunction contributes to hypoglycemia-induced endothelial dysfunction, but the mechanisms behind this linkage remain unknown. We attempt to determine whether clinically relevant low-glucose (LG) exposures acutely induce endothelial dysfunction through activation of the mitochondrial fission process. Characterization of mitochondrial morphology was carried out in cultured endothelial cells by using confocal microscopy. Isolated human arterioles were used to explore the effect LG-induced mitochondrial fission has on the formation of detrimental reactive oxygen species (ROS), bioavailability of nitric oxide (NO), and endothelial-dependent vascular relaxation. Fluorescence microscopy was employed to visualize changes in mitochondrial ROS and NO levels and videomicroscopy applied to measure vasodilation response. Pharmacological disruption of the profission protein Drp1 with Mdivi-1 during LG exposure reduced mitochondrial fragmentation among vascular endothelial cells (LG: 0.469; LG+Mdivi-1: 0.276; P = 0.003), prevented formation of vascular ROS (LG: 2.036; LG+Mdivi-1: 1.774; P = 0.005), increased the presence of NO (LG: 1.352; LG+Mdivi-1: 1.502; P = 0.048), and improved vascular dilation response to acetylcholine (LG: 31.6%; LG+Mdivi-1; 78.5% at maximum dose; P < 0.001). Additionally, decreased expression of Drp1 via siRNA knockdown during LG conditions also improved vascular relaxation. Exposure to LG imparts endothelial dysfunction coupled with altered mitochondrial phenotypes among isolated human arterioles. Disruption of Drp1 and subsequent mitochondrial fragmentation events prevents impaired vascular dilation, restores mitochondrial phenotype, and implicates mitochondrial fission as a primary

  14. Response properties of pigeon otolith afferents to linear acceleration

    NASA Technical Reports Server (NTRS)

    Si, X.; Angelaki, D. E.; Dickman, J. D.

    1997-01-01

    In the present study, the sensitivity to sinusoidal linear accelerations in the plane of the utricular macula was tested in afferents. The head orientation relative to the translation axis was varied in order to determine the head position that elicited the maximal and minimal responses for each afferent. The response gain and phase values obtained to 0.5-Hz and 2-Hz linear acceleration stimuli were then plotted as a function of head orientation and a modified cosine function was fit to the data. From the best-fit cosine function, the predicted head orientations that would produce the maximal and minimal response gains were estimated. The estimated maximum response gains to linear acceleration in the utricular plane for the afferents varied between 75 and 1420 spikes s-1 g-1. The mean maximal gains for all afferents to 0.5-Hz and 2-Hz sinusoidal linear acceleration stimuli were 282 and 367 spikes s-1 g-1, respectively. The minimal response gains were essentially zero for most units. The response phases always led linear acceleration and remained constant for each afferent, regardless of head orientation. These response characteristics indicate that otolith afferents are cosine tuned and behave as one-dimensional linear accelerometers. The directions of maximal sensitivity to linear acceleration for the afferents varied throughout the plane of the utricle; however, most vectors were directed out of the opposite ear near the interaural axis. The response dynamics of the afferents were tested using stimulus frequencies ranging between 0.25 Hz and 10 Hz (0.1 g peak acceleration). Across stimulus frequencies, most afferents had increasing gains and constant phase values. These dynamic properties for individual afferents were fit with a simple transfer function that included three parameters: a mechanical time constant, a gain constant, and a fractional order distributed adaptation operator.

  15. Three-dimensional mapping of oxygen tension in cortical arterioles before and after occlusion

    PubMed Central

    Kazmi, S. M. Shams; Salvaggio, Anthony J.; Estrada, Arnold D.; Hemati, Michael A.; Shaydyuk, Nazariy K.; Roussakis, Emannuel; Jones, Theresa A.; Vinogradov, Sergei A.; Dunn, Andrew K.

    2013-01-01

    Occlusions in single cortical microvessels lead to a reduction in oxygen supply, but this decrement has not been able to be quantified in three dimensions at the level of individual vessels using a single instrument. We demonstrate a combined optical system using two-photon phosphorescence lifetime and fluorescence microscopy (2PLM) to characterize the partial pressure of oxygen (pO2) in single descending cortical arterioles in the mouse brain before and after generating a targeted photothrombotic occlusion. Integrated real-time Laser Speckle Contrast Imaging (LSCI) provides wide-field perfusion maps that are used to monitor and guide the occlusion process while 2PLM maps changes in intravascular oxygen tension. We present the technique’s utility in highlighting the effects of vascular networking on the residual intravascular oxygen tensions measured after occlusion in three dimensions. PMID:23847732

  16. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen

    PubMed Central

    Ni, Heyu; Denis, Cécile V.; Subbarao, Sangeetha; Degen, Jay L.; Sato, Thomas N.; Hynes, Richard O.; Wagner, Denisa D.

    2000-01-01

    We used intravital microscopy to observe the formation of platelet plugs in ferric chloride–injured arterioles of live mice. With this model, we evaluated thrombus growth in mice lacking von Willebrand factor (vWF) and fibrinogen (Fg), the two key ligands known to mediate platelet adhesion and aggregation. In vWF–/– mice, despite the presence of arterial shear, delayed platelet adhesion occurred and stable thrombi formed. In many mice, a persisting high-shear channel never occluded. Abundant thrombi formed in Fg–/– mice, but they detached from the subendothelium, which ultimately caused downstream occlusion in all cases. Surprisingly, mice deficient in both vWF and Fg successfully formed thrombi with properties characteristic of both mutations, leading to vessel occlusion in the majority of vessels. Platelets of these doubly deficient mice specifically accumulated fibronectin in their α-granules, suggesting that fibronectin could be the ligand supporting the platelet aggregation. PMID:10930441

  17. Aberrant heartworm migration to the abdominal aorta and systemic arteriolitis in a dog presenting with vomiting and hemorrhagic diarrhea

    PubMed Central

    Grimes, Janet A.; Scott, Katherine D.; Edwards, John F.

    2016-01-01

    A 2-year-old Dachshund was presented for vomiting and diarrhea. Abdominal ultrasound revealed Dirofilaria immitis in the abdominal aorta and an avascular segment of small intestine. The dog was euthanized. Necropsy revealed D. immitis in the abdominal aorta and widespread necrotizing arteriolitis. This is a unique presentation of aberrant migration of D. immitis. PMID:26740703

  18. Involvement of matrix metalloproteinase-2 in medial hypertrophy of pulmonary arterioles in broiler chickens with pulmonary arterial hypertension.

    PubMed

    Tan, Xun; Chai, Juan; Bi, Shi-Cheng; Li, Jun-Jun; Li, Wen-Wen; Zhou, Ji-Yong

    2012-08-01

    Medial hypertrophy of pulmonary arterioles during pulmonary arterial hypertension (PAH) in humans is associated with enhanced proliferation of smooth muscle cells (SMCs). Elevated matrix metalloproteinase (MMP)-2 has been found in pulmonary artery SMCs (PA-SMCs) in humans with idiopathic PAH, leading to the hypothesis that MMP-2 contributes to the proliferation and migration of vascular SMCs in the pathogenesis of PAH. Rapidly growing meat-type (broiler) chickens provide a model of spontaneous PAH. The present study was conducted to determine whether MMP-2 is involved in the medial hypertrophy of pulmonary arterioles in this model. Cultured PA-SMCs from normal birds were used to evaluate the effect of MMPs on cell proliferation. Gelatin zymography showed that endothelin (ET)-1-induced proliferation of PA-SMCs was concomitant with increased pro- and active MMP-2 production. Reverse transcription PCR demonstrated upregulation of MMP-2 mRNA. However, PA-SMC proliferation was inhibited by the MMP inhibitors doxycycline and cis-9-octadecenoyl-N-hydroxylamide. In vivo experiments revealed a significant increase of MMP-2 expression in hypertrophied pulmonary arterioles of PAH broiler chickens, which was positively correlated with wall thickness and medial hypertrophy. MMP-2 may contribute to medial hypertrophy in pulmonary arterioles during PAH in broiler chickens by enhancing the proliferation of vascular SMCs.

  19. Effect of Microgravity on Afferent Innervation

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Presentations and publications are: (1) an audiovisual summary web presentation on results from SLM-MIR avian experiments. A color presentation summarizing results from the SLM-MIR and STS-29 avian experiments; (2) color threshold and ratio of S 100B MAP5, NF68/200, GABA and GAD; (3) chicken (Gallus domesticus) inner ear afferents; (4) microgravity in the STS-29 Space Shuttle Discovery affected the vestibular system of chick embryos; (5) expression of S 100B in sensory and secretory cells of the vertebrate inner ear; (6) otoconia biogenesis, phylogeny, composition and functional attributes;(7) the glycan keratin sulfate in inner ear crystals; (8) elliptical-P cells in the avian perilymphatic interface of the tegmentum vasculosum; and (9) LAMP2c and S100B upregulation in brain stem after VIIIth nerve deafferentation.

  20. Adaptation of vasomotor function of human coronary arterioles to the simultaneous presence of obesity and hypertension.

    PubMed

    Fulop, Tibor; Jebelovszki, Eva; Erdei, Nora; Szerafin, Tamas; Forster, Tamas; Edes, Istvan; Koller, Akos; Bagi, Zsolt

    2007-11-01

    We hypothesized that simultaneous presence of obesity and hypertension activates adaptive vascular mechanisms affecting dilations of human coronary arterioles. Agonist-induced dilations were assessed in isolated pressurized coronary arterioles from patients (n=38) who underwent cardiac surgery. Among normotensives we found that dilations to bradykinin (BK) and the NO-donor, sodium-nitroprusside (SNP) were reduced in obese subjects (BK, 10(-7) mol/L, lean: 90+/-4%, obese: 64+/-7%; SNP, 10(-6) mol/L, lean: 89+/-7%, obese: 76+/-5%). However, among hypertensives, both BK- and SNP-induced dilations were significantly enhanced in obese patients, when compared with lean individuals (BK, lean: 71+/-7%, obese: 85+/-3%; SNP, lean: 60+/-6%, obese: 83+/-2%). Correspondingly, in hypertensive patients, but not in those of normotensives, a positive correlation was found between body mass index (BMI) and BK-induced (P=0.036, r=0.46), and also SNP-evoked (P=0.031, r=0.44) coronary dilations. Moreover, in additional 55 hypertensive patients flow-mediated (FMD) and nitroglycerin (NTG)-induced dilations of the brachial artery were assessed. In obese hypertensive individuals, FMD- and NTG-induced dilations were greater (FMD: 6.2+/-0.7%, NTG: 17.2+/-0.9%), than in lean hypertensive patients (FMD: 3.7+/-0.6%, NTG: 13.6+/-1.1%). Correspondingly, FMD- and NTG-induced dilations were positively correlated with BMI (P=0.020, r=0.31 and P=0.033, r=0.29, respectively). These findings are the first to suggest that obesity may lead to activation of adaptive vascular mechanisms to enhance the dilator function of coronary and peripheral arterial vessels in hypertensive patients.

  1. Relative magnitude of vascular reactivity in the major arterioles of the retina.

    PubMed

    Sehi, Mitra; Tsui, Edmund; Cheng, Richard; Wan, Jennifer; Wong, Tien; Dorner, Stephanie; Fisher, Joseph; Hudson, Christopher

    2012-03-01

    The relative magnitude of vascular reactivity to inhaled gas stimuli in the major retinal arterioles has not been systematically investigated. The purpose of this study was to compare the magnitude of retinal vascular reactivity in response to inhaled gas provocation at equivalent measurement sites in the superior-, and inferior-, temporal retinal arterioles (STA, ITA). One randomly selected eye of each of 17 healthy volunteers (age 24.4 ± 4.7) was prospectively enrolled. Volunteers were connected to a sequential gas delivery circuit and a computer-controlled gas blender (RespirAct™, Thornhill Research Inc., Canada) and underwent an isocapnic hyperoxic challenge i.e. P(ET)O(2) of 500 mm Hg with P(ET)CO(2) maintained at 38 mm Hg during baseline and hyperoxia. Four retinal hemodynamic measurements were acquired using bi-directional laser Doppler velocimetry and simultaneous vessel densitometry (Canon Laser Blood Flowmeter, CLBF-100, Japan) at equivalent positions on the STA and ITA. Statistical analysis was performed using linear mixed-effect models. During the hyperoxic phase, the vessel diameter (STA p=0.004; ITA p=0.003), blood velocity (STA p<0.001; ITA p<0.001) and flow (STA p<0.001; ITA p<0.001) decreased in both the STA and the ITA relative to baseline. The diameter, velocity and flow were equivalent between STA and ITA at baseline and during hyperoxia; and their magnitude of change remained comparable with hyperoxia (p>0.05). The magnitude of retinal arteriolar vascular reactivity in response to isocapnic hyperoxic inhaled gas challenge was not significantly different between the STA and ITA. However, the correlation analysis did not reveal a significant relationship between the percentage changes in diameter, velocity and flow of the STA and ITA and did not demonstrate equal responses from the STA and ITA to gas provocation. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Calcium responses induced by acetylcholine in submucosal arterioles of the guinea-pig small intestine

    PubMed Central

    Fukuta, Hiroyasu; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

    1999-01-01

    Calcium responses induced by brief stimulation with acetylcholine (ACh) were assessed from the fluorescence changes in fura-2 loaded submucosal arterioles of the guinea-pig small intestine. Initially, 1–1.5 h after loading with fura-2 (fresh tissues), ACh increased [Ca2+]i in a concentration-dependent manner. This response diminished with time, and finally disappeared in 2–3 h (old tissues). Ba2+ elevated [Ca2+]i to a similar extent in both fresh and old tissues. ACh further increased the Ba2+-elevated [Ca2+]i in fresh tissues, but reduced it in old tissues. Responses were not affected by either indomethacin or nitroarginine. In fresh mesenteric arteries, mechanical removal of endothelial cells abolished the ACh-induced increase in [Ca2+]i, with no alteration of [Ca2+]i at rest and during elevation with Ba2+. In the presence of indomethacin and nitroarginine, high-K+ solution elevated [Ca2+]i in both fresh and old tissues. Subsequent addition of ACh further increased [Ca2+]i in fresh tissues without changing it in old tissues. Proadifen, an inhibitor of the enzyme cytochrome P450 mono-oxygenase, inhibited the ACh-induced changes in [Ca2+]i in both fresh and Ba2+-stimulated old tissues. It also inhibited the ACh-induced hyperpolarization. In fresh tissues, the ACh-induced Ca2+ response was not changed by apamin, charybdotoxin (CTX), 4-aminopyridine (4-AP) or glibenclamide. In old tissues in which [Ca2+]i had previously been elevated with Ba2+, the ACh-induced Ca2+ response was inhibited by CTX but not by apamin, 4-AP or glibenclamide. It is concluded that in submucosal arterioles, ACh elevates endothelial [Ca2+]i and reduces muscular [Ca2+]i, probably through the hyperpolarization of endothelial or smooth muscle membrane by activating CTX-sensitive K+ channels. PMID:10050015

  3. Retinal Arterioles in Hypo-, Normo-, and Hypertensive Subjects Measured Using Adaptive Optics

    PubMed Central

    Hillard, Jacob G.; Gast, Thomas J.; Chui, Toco Y.P.; Sapir, Dan; Burns, Stephen A.

    2016-01-01

    Purpose Small artery and arteriolar walls thicken due to elevated blood pressure. Vascular wall thickness show a correlation with hypertensive subject history and risk for stroke and cardiovascular events. Methods The inner and outer diameter of retinal arterioles from less than 10 to over 150 μm were measured using a multiply scattered light adaptive optics scanning laser ophthalmoscope (AOSLO). These measurements were made on three populations, one with habitual blood pressures less than 100/70 mm Hg, one with normal blood pressures without medication, and one with managed essential hypertension. Results The wall to lumen ratio was largest for the smallest arterioles for all three populations. Data from the hypotensive group had a linear relationship between outer and inner diameters (r2 = 0.99) suggesting a similar wall structure in individuals prior to elevated blood pressures. Hypertensive subjects fell below the 95% confidence limits for the hypotensive relationship and had larger wall to lumen ratios and the normotensive group results fell between the other two groups. Conclusion High-resolution retinal imaging of subjects with essential hypertension showed a significant decrease in vessel inner diameter for a given outer diameter, and increases in wall to lumen ratio and wall cross-sectional areas over the entire range of vessel diameters and suggests that correcting for vessel size may improve the ability to identify significant vascular changes. Translational Relevance High-resolution imaging allows precise measurement of vasculature and by comparing results across risk populations may allow improved identification of individuals undergoing hypertensive arterial wall remodeling. PMID:27617182

  4. Measurement of hydraulic conductivity in isolated arterioles of rat brain cortex.

    PubMed

    Kimura, M; Dietrich, H H; Huxley, V H; Reichner, D R; Dacey, R G

    1993-06-01

    We have developed a new method for quantification of arteriolar hydraulic conductivity (Lp) from isolated rat brain vessels. The volume flux of water per unit surface area across the arteriole wall (Jv/S) was assessed from measurements of silicon oil drop movement within an occluded vessel at two to three pressures (between 20 and 70 mmHg); the Lp was derived from the slope of the relationship between Jv/S and applied pressure. Lp was measured in isolated cerebral arterioles 1) at room temperature (22 degrees C) without spontaneous vessel tone (control Lp; n = 11), 2) at room temperature with 10(-4) M adenosine (n = 5), and 3) at 37 degrees C with vessels dilated submaximally with 10(-4) M adenosine (n = 6). Lp at 22 degrees C without adenosine was 13.2 +/- 4.2 x 10(-9) (+/- SE) cm.s-1.cmH2O-1 for all vessels studied. Lp values ranged from 1.2 to 44.1 x 10(-9) cm.s-1.cmH2O-1 with a median value that was 5.9 x 10(-9) cm.s-1.cmH2O-1. Lp increased significantly (on average, 2.6-fold) with adenosine at 37 degrees C but not with adenosine at 22 degrees C. Control Lp bore no relationship to either the development of spontaneous tone or the diameter response to pH change, two recognized indicators of vessel viability.

  5. MACROMOLECULE PERMEABILITY OF IN SITU AND EXCISED RODENT SKELETAL MUSCLE ARTERIOLES AND VENULES.

    PubMed Central

    Sarelius, Ingrid H.; Kuebel, Julia M.; Wang, Jianjie; Huxley., Virginia H.

    2006-01-01

    In microvessels, acute inflammation is typified by an increase in leukocyte-endothelial cell interactions culminating in leukocyte transmigration into the tissue, and increased permeability to water and solutes, resulting in tissue edema. The goal of this study was to establish a method to quantify solute permeability (Ps) changes in microvessels in intact predominantly blood perfused networks in which leukocyte transmigratory behavior could be precisely described using established paradigms. We used intravital confocal microscopy to measure solute (BSA) flux across microvessel walls, hence Ps. The quantitative fluorescence approach of Huxley et al (Am. J. Physiol. 252:H188–H197,1987) was adapted to the imaged confocal tissue slice in which the fluorescent source volume and source surface area of the microvessel were restricted to the region of vessel that was contained within the imaged confocal tissue section. Ps measurements were made in intact cremaster muscle microvasculature of anesthetized mice and compared to measurements of Ps made in isolated rat skeletal muscle microvessels. Mouse arteriolar Ps was 9.9±1.1 × 10−7cm.sec−1 (n=16), which was not different from 8.4±1.3 × 10−7cm.sec−1 (n=6) in rat arterioles. Values in venules were significantly (p<.05) higher: 44.4±7.9 × 10−7cm.sec−1 (n=14) in mice and 25.0±3.7 × 10−7cm.sec−1 in rats. Convective coupling was estimated to contibute <10% to the measured Ps in both microvessel types and both animal models. We conclude that this approach provides an appropriate quantification of Ps in the intact microvasculature, and that arteriolar Ps, while lower than in venules, is nevertheless consistent with arterioles being a significant source of interstitial protein. PMID:16126813

  6. Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats.

    PubMed

    Sogawa, Kenji; Nagaoka, Taiji; Izumi, Naohiro; Nakabayashi, Seigo; Yoshida, Akitoshi

    2010-05-01

    To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia. Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment. The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK-induced increase in RBF during hyperglycemia. The results suggest that acute hyperglycemia increases RBF via increased osmolality and may cause retinal endothelial dysfunction partially via increased oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.

  7. Myeloperoxidase evokes substantial vasomotor responses in isolated skeletal muscle arterioles of the rat

    PubMed Central

    Csató, V; Pető, A; Fülöp, G Á; Rutkai, I; Pásztor, E T; Fagyas, M; Kalász, J; Édes, I; Tóth, A; Papp, Z

    2015-01-01

    Aims Myeloperoxidase (MPO) catalyses the formation of a wide variety of oxidants, including hypochlorous acid (HOCl), and contributes to cardiovascular disease progression. We hypothesized that during its action MPO evokes substantial vasomotor responses. Methods Following exposure to MPO (1.92 mU mL−1) in the presence of increasing concentrations of hydrogen peroxide (H2O2), changes in arteriolar diameter of isolated gracilis skeletal muscle arterioles (SMAs) and coronary arterioles (CAs) and in the isometric force in basilar arteries (BAs) of the rat were monitored. Results Myeloperoxidase increased vascular tone to different degrees in CAs, SMAs and BAs. The mechanism of increased vasoconstriction was studied in detail in SMAs. MPO-evoked vasoconstrictions were prevented by the MPO inhibitor 4-aminobenzhydrazide (50 μm), by endothelium removal in the SMAs. Surprisingly, the HOCl scavenger L-methionine (100 μm), the thromboxane A2 (TXA2) antagonist SQ-29548 (1 μm) or the non-specific cyclooxygenase (COX) antagonist indomethacin (1 μm) converted the MPO-evoked vasoconstrictions to pronounced vasodilations in SMAs, not seen in the presence of H2O2. In contrast to noradrenaline-induced vasoconstrictions, the MPO-evoked vasoconstrictions were not accompanied by significant increases in arteriolar [Ca2+] levels in SMAs. Conclusion These data showed that H2O2-derived HOCl to be a potent vasoconstrictor upon MPO application. HOCl activated the COX pathway, causing the synthesis and release of a TXA2-like substance to increase the Ca2+ sensitivity of the contractile apparatus in vascular smooth muscle cells and thereby to augment H2O2-evoked vasoconstrictions. Nevertheless, inhibition of the HOCl–COX–TXA2 pathway unmasked the effects of additional MPO-derived radicals with a marked vasodilatory potential in SMAs. PMID:25760778

  8. Chicken (Gallus domesticus) inner ear afferents

    NASA Technical Reports Server (NTRS)

    Hara, H.; Chen, X.; Hartsfield, J. F.; Hara, J.; Martin, D.; Fermin, C. D.

    1998-01-01

    Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

  9. Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion.

    PubMed

    Spray, S; Johansson, S E; Radziwon-Balicka, A; Haanes, K A; Warfvinge, K; Povlsen, G K; Kelly, P A T; Edvinsson, L

    2017-08-01

    Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature. © 2016 Scandinavian Physiological Society. Published by John Wiley

  10. Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension.

    PubMed

    Goodwill, Adam G; James, Milinda E; Frisbee, Jefferson C

    2008-10-01

    This study determined if altered vascular prostacyclin (PGI(2)) and/or thromboxane A(2) (TxA(2)) production with reduced Po(2) contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po(2) under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po(2). Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI(2) production with reduced Po(2) was similar between strains, although TxA(2) production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH(2)/TxA(2) receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA(2), which competes against the vasodilator influences of PGI(2). These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA(2) production and may blunt vascular sensitivity to PGI(2).

  11. Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

    PubMed

    Amann, K; Törnig, J; Flechtenmacher, C; Nabokov, A; Mall, G; Ritz, E

    1995-11-01

    Abnormalities in cardiovascular structures, e.g. LV hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the genesis of cardiac fibrosis. The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well. Male SD rats were sham operated or subtotally nephrectomized and maintained for 2 weeks. Subgroups of subtotally nephrectomized (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PTH was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). In random samples of the left ventricle, wall thickness of arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 138 +/- 8.4 mmHg, SNX-PTX+solvent 142 +/- 5.2 mmHg; SNX-PTX+PTH 148 +/- 5.7 mmHg). PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial-cell activation. The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).

  12. Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat.

    PubMed

    Rudomin, P; Lomelí, J

    2007-01-01

    We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation

  13. Tonic postganglionic sympathetic inhibition induced by afferent renal nerves?

    PubMed

    Ditting, Tilmann; Freisinger, Wolfgang; Siegel, Kirsten; Fiedler, Christian; Small, Lisa; Neuhuber, Winfried; Heinlein, Sonja; Reeh, Peter W; Schmieder, Roland E; Veelken, Roland

    2012-02-01

    Other than efferent sympathetic innervation, the kidney has peptidergic afferent fibers expressing TRPV1 receptors and releasing substance P. We tested the hypothesis that stimulation of afferent renal nerve activity with the TRPV1 agonist capsaicin inhibits efferent renal sympathetic nerve activity tonically by a neurokinin 1 receptor-dependant mechanism. Anesthetized Sprague-Dawley rats were instrumented as follows: (1) arterial and venous catheters for recording of blood pressure and heart rate and drug administration; (2) left-sided renal arterial catheter for selective intrarenal administration of the TRPV1 agonist capsaicin (3.3, 6.6, 10, 33*10(-7) m; 10 μL; after 15, 30, 45, and 60 minutes, respectively) to stimulate afferent renal nerve activity; (3) right-sided bipolar electrode for continuous renal sympathetic nerve recording; and (4) specialized renal pelvic and renal artery catheters to separate pelvic from intrarenal afferent activity. Before and after intrarenal capsaicin application, increasing intravenous doses of the neurokinin 1 receptor blocker RP67580 were given. Intrarenal capsaicin decreased integrated renal sympathetic activity from 65.4±13.0 mV*s (baseline) to 12.8±3.2 mV*s (minimum; P<0.01). This sustained renal sympathetic inhibition reached its minimum within 70 minutes and was not directly linked to the transient electric afferent response to be expected with intrarenal capsaicin. Suppressed renal sympathetic activity transiently but completely recovered after intravenous administration of the neurokinin 1 blocker (maximum: 120.3±19.4 mV*s; P<0.01). Intrarenal afferent activity could be unequivocally separated from pelvic afferent activity. For the first time we provide direct evidence that afferent intrarenal nerves provide a tonically acting sympathoinhibitory system, which seems to be rather mediated by neurokinin release acting via neurokinin 1 receptor pathways rather than by electric afferent effects on central sympathetic

  14. Topical hexylaminolevulinate and aminolevulinic acid photodynamic therapy: complete arteriole vasoconstriction occurs frequently and depends on protoporphyrin IX concentration in vessel wall.

    PubMed

    Middelburg, T A; de Bruijn, H S; Tettero, L; van der Ploeg van den Heuvel, A; Neumann, H A M; de Haas, E R M; Robinson, D J

    2013-09-05

    Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Muscle afferent excitability testing in spinal root-intact rats: dissociating peripheral afferent and efferent volleys generated by intraspinal microstimulation.

    PubMed

    Tomatsu, Saeka; Kim, Geehee; Confais, Joachim; Seki, Kazuhiko

    2017-02-01

    Presynaptic inhibition of the sensory input from the periphery to the spinal cord can be evaluated directly by intra-axonal recording of primary afferent depolarization (PAD) or indirectly by intraspinal microstimulation (excitability testing). Excitability testing is superior for use in normal behaving animals, because this methodology bypasses the technically challenging intra-axonal recording. However, use of excitability testing on the muscle or joint afferent in intact animals presents its own technical challenges. Because these afferents, in many cases, are mixed with motor axons in the peripheral nervous system, it is crucial to dissociate antidromic volleys in the primary afferents from orthodromic volleys in the motor axon, both of which are evoked by intraspinal microstimulation. We have demonstrated in rats that application of a paired stimulation protocol with a short interstimulus interval (ISI) successfully dissociated the antidromic volley in the nerve innervating the medial gastrocnemius muscle. By using a 2-ms ISI, the amplitude of the volleys evoked by the second stimulation was decreased in dorsal root-sectioned rats, but the amplitude did not change or was slightly increased in ventral root-sectioned rats. Excitability testing in rats with intact spinal roots indicated that the putative antidromic volleys exhibited dominant primary afferent depolarization, which was reasonably induced from the more dorsal side of the spinal cord. We concluded that excitability testing with a paired-pulse protocol can be used for studying presynaptic inhibition of somatosensory afferents in animals with intact spinal roots.NEW & NOTEWORTHY Excitability testing of primary afferents has been used to evaluate presynaptic modulation of synaptic transmission in experiments conducted in vivo. However, to apply this method to muscle afferents of animals with intact spinal roots, it is crucial to dissociate antidromic and orthodromic volleys induced by spinal

  16. Primary afferent response to signals in the intestinal lumen.

    PubMed

    Raybould, H

    2001-02-01

    The first recordings of vagal afferent nerve fibre activity were performed by Paintal in the early 1950s. In these experiments, he showed that phenyldiguanide (later recognized as a 5-HT3 receptor agonist) stimulated the firing of C-fibres innervating the intestine. In the following years, ample physiological and psychological studies have demonstrated the importance of afferent information arising from the gut in the regulation of gastrointestinal function and behaviour. Many stimuli are capable of eliciting these functional effects and of stimulating afferent fibre discharge, including mechanical, chemical, nutrient- and immune-derived stimuli. Studies in the last 10 years have begun to focus on the precise sensory transduction mechanisms by which these visceral primary afferent nerve terminals are activated and, like the contribution by Zhu et al. in this issue of The Journal of Physiology, are revealing some novel and exciting findings.

  17. Vagal afferent stimulation as a cardioprotective strategy? Introducing the concept.

    PubMed

    Fallen, Ernest L

    2005-10-01

    The effect of vagal afferent signaling on cardioinhibition has been well known for over 130 years. Both experimental and clinical studies have demonstrated not only the potential adverse effect of unrestrained sympathoexcitation in high risk patients with ischemic heart disease but the potential for cardioprotection by programmed vagal activity. The vasodepressor and negative chronotropic effects of efferent vagal stimulation has been a cause for concern. However it is becoming clear that favorable shifts towards increased cardiac vagal modulation can be achieved by vagal afferent nerve stimulation. This phasic effect appears to operate though central medullary pathways. Thus by engaging vagal afferent fibers in humans there is the possibility that one can exploit the benefits of central cardioinhibition without adversely affecting heart rate, respiration or hemodynamics. This commentary explores the background and rationale for considering vagal afferent stimulation as a plausible cardioprotective strategy.

  18. Vagal Afferent Innervation of the Airways in Health and Disease

    PubMed Central

    Mazzone, Stuart B.

    2016-01-01

    Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions. PMID:27279650

  19. Afferent control of human stance and gait: evidence for blocking of group I afferents during gait.

    PubMed

    Dietz, V; Quintern, J; Berger, W

    1985-01-01

    The cerebral potentials (c.p.) evoked by electrical stimulation of the tibial nerve during stance and in the various phases of gait of normal subjects were compared with the c.p. and leg muscle e.m.g. responses evoked by perturbations of stance and gait. Over the whole step cycle of gait the c.p. evoked by an electrical stimulus were of smaller amplitude (3 microV and 9 microV, respectively) than that seen in the stance condition, and appeared with a longer latency (mean times to first positive peak: 63 and 43 ms, respectively). When the electrical stimulus was applied during stance after ischaemic blockade of group I afferents, the c.p. were similar to those evoked during gait. The c.p. evoked by perturbations were larger in amplitude than those produced by the electrical stimulus, but similar in latencies in both gait and stance (mean 26 microV and 40 microV; 65 ms and 42 ms, respectively) and configurations. The large gastrocnemius e.m.g. responses evoked by the stance and gait perturbations arose with a latency of 65 to 70 ms. Only in the stance condition was a smaller, shorter latency (40 ms) response seen. It is concluded that during gait the signals of group I afferents are blocked at both segmental and supraspinal levels which was tested by tibial nerve stimulation. It is suggested that the e.m.g. responses induced in the leg by gait perturbations are evoked by group II afferents and mediated via a spinal pathway. The c.p. evoked during gait most probably reflect the processing of this group II input by supraspinal motor centres for the coordination of widespread arm and trunk muscle activation, necessary to restablish body equilibrium.

  20. Aging and exercise training reduce testes microvascular Po2 and alter vasoconstrictor responsiveness in testicular arterioles

    PubMed Central

    Dominguez, James M.; Davis, Robert T.; McCullough, Danielle J.; Stabley, John N.

    2011-01-01

    Testicular function and associated testosterone concentration decline with advancing age, and an impaired O2 supply may contribute, in part, to this reduction. We hypothesized that there would be a reduced microvascular Po2 (Po2m) in the testes from aged rats, and this reduced Po2m would be associated with impaired vasomotor control in isolated resistance arterioles. In addition, given the positive effect of exercise on microvascular Po2 and arteriolar function, we further hypothesized that there would be an enhanced Po2m in the testes from aged animals after aerobic exercise training. Testicular Po2m was measured in vivo via phosphorescence quenching in young and aged sedentary (SED) and exercise-trained (ET; 15 m/min treadmill walking, 15-degree incline, 5 days/wk for 10 wk) male Fischer-344 rats. Vasoconstriction to α-adrenergic [norepinephrine (NE) and phenylephrine (PE)] and myogenic stimuli in testicular arterioles was assessed in vitro. In the SED animals, testicular Po2m was reduced by ∼50% with old age (aged SED 11.8 ± 1.9 vs. young SED 22.1 ± 1.1 mmHg; P = 0.0001). Contrary to our hypothesis, exercise training did not alter Po2m in the aged group and reduced testicular Po2m in the young animals, abolishing age-related differences (young ET, 10.0 ± 0.8 vs. aged ET, 10.7 ± 0.9 mmHg; P = 0.37). Vasoconstrictor responsiveness to NE and PE was diminished in aged compared with young (NE: young SED, 58 ± 2 vs. aged SED, 47 ± 2%; P = 0.001) (PE: young SED, 51 ± 3 vs. aged SED, 36 ± 5%; P = 0.008). Exercise training did not alter maximal vasoconstriction to NE in young or aged groups. In summary, advancing age is associated with a reduced testis Po2m and impaired adrenergic vasoconstriction. The diminished testicular microvascular driving pressure of O2 and associated vascular dysfunction provides mechanistic insight into the old age-related decrease in testicular function, and a reduced Po2m may contribute, in part, to reduced fertility markers after

  1. Acid-sensing by airway afferent nerves

    PubMed Central

    Lee, Lu-Yuan; Gu, Qihai; Xu, Fadi; Hong, Ju-Lun

    2013-01-01

    Inhalation of acid aerosol or aspiration of acid solution evokes a stimulatory effect on airway C-fiber and Aδ afferents, which in turn causes airway irritation and triggers an array of defense reflex responses (e.g., cough, reflex bronchoconstriction, etc.). Tissue acidosis can also occur locally in the respiratory tract as a result of ischemia or inflammation, such as in the airways of asthmatic patients during exacerbation. The action of proton on the airway sensory neurons is generated by activation of two different current species: a transient (rapidly activating and inactivating) current mediated through the acid-sensing ion channels, and a slowly activating and sustained current mediated through the transient receptor potential vanilloid type 1 (TRPV1) receptor. In view of the recent findings that the expression and/or sensitivity of TRPV1 are up-regulated in the airway sensory nerves during chronic inflammatory reaction, the proton-evoked irritant effects on these nerves may play an important part in the manifestation of various symptoms associated with airway inflammatory diseases. PMID:23524016

  2. Cystitis increases colorectal afferent sensitivity in the mouse.

    PubMed

    Brumovsky, Pablo Rodolfo; Feng, Bin; Xu, Linjing; McCarthy, Carly Jane; Gebhart, G F

    2009-12-01

    Studies in humans and rodents suggest that colon inflammation promotes urinary bladder hypersensitivity and, conversely, that cystitis contributes to colon hypersensitivity, events referred to as cross-organ sensitization. To investigate a potential peripheral mechanism, we examined whether cystitis alters the sensitivity of pelvic nerve colorectal afferents. Male C57BL/6 mice were treated with cyclophosphamide (CYP) or saline, and the mechanosensitive properties of single afferent fibers innervating the colorectum were studied with an in vitro preparation. In addition, mechanosensitive receptive endings were exposed to an inflammatory soup (IS) to study sensitization. Urinary bladder mechanosensitive afferents were also tested. We found that baseline responses of stretch-sensitive colorectal afferents did not differ between treatment groups. Whereas IS excited a proportion of colorectal afferents CYP treatment did not alter the magnitude of this response. However, the number of stretch-sensitive fibers excited by IS was increased relative to saline-treated mice. Responses to IS were not altered by CYP treatment, but the proportion of IS-responsive fibers was increased relative to saline-treated mice. In bladder, IS application increased responses of muscular afferents to stretch, although no differences were detected between saline- and CYP-treated mice. In contrast, their chemosensitivity to IS was decreased in the CYP-treated group. Histological examination revealed no changes in colorectum and modest edema and infiltration in the urinary bladder of CYP-treated mice. In conclusion, CYP treatment increased mechanical sensitivity of colorectal muscular afferents and increased the proportion of chemosensitive colorectal afferents. These data support a peripheral contribution to cross-organ sensitization of pelvic organs.

  3. Presynaptic selection of afferent inflow in the spinal cord.

    PubMed

    Rudomin, P

    1999-01-01

    The synaptic effectiveness of sensory fibers ending in the spinal cord of vertebrates can be centrally controlled by means of specific sets of GABAergic interneurons that make axo-axonic synapses with the terminal arborizations of the afferent fibers. In the steady state, the intracellular concentration of chloride ions in these terminals is higher than that predicted from a passive distribution, because of an active transport mechanism. Following the release of GABA by spinal interneurons and activation of GABA(A) receptors in the afferent terminals, there is an outwardly directed efflux of chloride ions that produces primary afferent depolarization (PAD) and reduces transmitter release (presynaptic inhibition). Studies made by intrafiber recording of PAD, or by measuring changes in the intraspinal threshold of single afferent terminals (which is reduced during PAD), have further indicated that muscle and cutaneous afferents have distinctive, but modifiable PAD patterns in response to segmental and descending stimuli. This has suggested that PAD and presynaptic inhibition in the various types of afferents is mediated by separate sets of last-order GABAergic interneurons. Direct activation, by means of intraspinal microstimulation, of single or small groups of last-order PAD-mediating interneurons shows that the monosynaptic PAD elicited in Ia and Ib afferents can remain confined to some sets of the intraspinal collaterals and not spread to nearby collaterals. The local character of PAD allows cutaneous and descending inputs to selectively inhibit the PAD of segmental and ascending intraspinal collaterals of individual muscle spindle afferents. It thus seems that the intraspinal branches of the sensory fibers are not hard wired routes that diverge excitation to spinal neurons, but are instead dynamic pathways that can be centrally controlled to address information to selected neuronal targets. This feature appears to play an important role in the selection of

  4. Visceral perception: sensory transduction in visceral afferents and nutrients.

    PubMed

    Raybould, H E

    2002-07-01

    The possible mechanisms that may be involved in nutrient detection in the wall of the gastrointestinal tract are reviewed. There is strong functional and electrophysiological evidence that both intrinsic and extrinsic primary afferent neurones mediate mechano- and chemosensitive responses in the gastrointestinal tract. This review focuses on the extrinsic afferent pathways as these are the ones that convey information to the central nervous system which is clearly necessary for perception to occur.

  5. Tyrosine Hydroxylase Expression in Type II Cochlear Afferents in Mice.

    PubMed

    Vyas, Pankhuri; Wu, Jingjing Sherry; Zimmerman, Amanda; Fuchs, Paul; Glowatzki, Elisabeth

    2017-02-01

    Acoustic information propagates from the ear to the brain via spiral ganglion neurons that innervate hair cells in the cochlea. These afferents include unmyelinated type II fibers that constitute 5 % of the total, the majority being myelinated type I neurons. Lack of specific genetic markers of type II afferents in the cochlea has been a roadblock in studying their functional role. Unexpectedly, type II afferents were visualized by reporter proteins induced by tyrosine hydroxylase (TH)-driven Cre recombinase. The present study was designed to determine whether TH-driven Cre recombinase (TH-2A-CreER) provides a selective and reliable tool for identification and genetic manipulation of type II rather than type I cochlear afferents. The "TH-2A-CreER neurons" radiated from the spiral lamina, crossed the tunnel of Corti, turned towards the base of the cochlea, and traveled beneath the rows of outer hair cells. Neither the processes nor the somata of TH-2A-CreER neurons were labeled by antibodies that specifically labeled type I afferents and medial efferents. TH-2A-CreER-positive processes partially co-labeled with antibodies to peripherin, a known marker of type II afferents. Individual TH-2A-CreER neurons gave off short branches contacting 7-25 outer hair cells (OHCs). Only a fraction of TH-2A-CreER boutons were associated with CtBP2-immunopositive ribbons. These results show that TH-2A-CreER provides a selective marker for type II versus type I afferents and can be used to describe the morphology and arborization pattern of type II cochlear afferents in the mouse cochlea.

  6. The influence of pain on masseter spindle afferent discharge.

    PubMed

    Capra, Norman F; Hisley, Calvin K; Masri, Radi M

    2007-04-01

    Muscle spindles provide proprioceptive feedback supporting normal patterns of motor activity and kinesthetic sensibility. During mastication, jaw muscle spindles play an important role in monitoring and regulating the chewing cycle and the bite forces generated during mastication. Both acute and chronic orofacial pain disorders are associated with changes in proprioceptive feedback and motor function. Experimental jaw muscle pain also alters the normal response of masseter spindle afferents to ramp and hold jaw movements. It has been proposed that altered motor function and proprioceptive input results from group III muscle afferent modulation of the fusimotor system which alters spindle afferent sensitivity in limb muscles. The response to nociceptive stimuli may enhance or reduce the response of spindle afferents to proprioceptive stimuli. Several experimental observations suggesting the possibility that a similar mechanism also functions in jaw muscles are presented in this report. First, evidence is provided to show that nociceptive stimulation of the masseter muscle primarily influences the amplitude sensitivity of spindle afferents with relatively little effect on the dynamic sensitivity. Second, reversible inactivation of the caudal trigeminal nuclei attenuates the nociceptive modulation of spindle afferents. Finally, functionally identified gamma-motoneurons in the trigeminal motor nucleus are modulated by intramuscular injection with algesic substances. Taken together, these results suggest that pain-induced modulation of spindle afferent responses are mediated by small diameter muscle afferents and that this modulation is dependent, in part, on the relay of muscle nociceptive information from trigeminal subnucleus caudalis onto trigeminal gamma-motoneurons. The implication of these results will be considered in light of current theories on the relationship between jaw muscle pain and oral motor function.

  7. Differential central projections of vestibular afferents in pigeons

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.; Fang, Q.

    1996-01-01

    The question of whether a differential distribution of vestibular afferent information to central nuclear neurons is present in pigeons was studied using neural tracer compounds. Discrete tracing of afferent fibers innervating the individual semicircular canal and otolith organs was produced by sectioning individual branches of the vestibular nerve that innervate the different receptor organs and applying crystals of horseradish peroxidase, or a horseradish peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and transport. Afferent fibers and their terminal distributions within the brainstem and cerebellum were visualized subsequently. Discrete areas in the pigeon central nervous system that receive primary vestibular input include the superior, dorsal lateral, ventral lateral, medial, descending, and tangential vestibular nuclei; the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal afferents projected heavily to medial regions in the superior and descending vestibular nuclei as well as the A group. Vertical canal projections to the medial and lateral vestibular nuclei were observed but were less prominent. Horizontal canal projections to the superior and descending vestibular nuclei were much more centrally located than those of the vertical canals. A more substantial projection to the medial and lateral vestibular nuclei was seen with horizontal canal afferents compared to vertical canal fibers. Afferents innervating the utricle and saccule terminated generally in the lateral regions of all vestibular nuclei in areas that were separate from the projections of the semicircular canals. In addition, utricular fibers projected to regions in the vestibular nuclei that overlapped with the horizontal semicircular canal terminal fields, whereas saccular afferents projected to regions that received vertical canal fiber terminations. Lagenar

  8. Differential central projections of vestibular afferents in pigeons

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.; Fang, Q.

    1996-01-01

    The question of whether a differential distribution of vestibular afferent information to central nuclear neurons is present in pigeons was studied using neural tracer compounds. Discrete tracing of afferent fibers innervating the individual semicircular canal and otolith organs was produced by sectioning individual branches of the vestibular nerve that innervate the different receptor organs and applying crystals of horseradish peroxidase, or a horseradish peroxidase/cholera toxin mixture, or a biocytin compound for neuronal uptake and transport. Afferent fibers and their terminal distributions within the brainstem and cerebellum were visualized subsequently. Discrete areas in the pigeon central nervous system that receive primary vestibular input include the superior, dorsal lateral, ventral lateral, medial, descending, and tangential vestibular nuclei; the A and B groups; the intermediate, medial, and lateral cerebellar nuclei; and the nodulus, the uvula, and the paraflocculus. Generally, the vertical canal afferents projected heavily to medial regions in the superior and descending vestibular nuclei as well as the A group. Vertical canal projections to the medial and lateral vestibular nuclei were observed but were less prominent. Horizontal canal projections to the superior and descending vestibular nuclei were much more centrally located than those of the vertical canals. A more substantial projection to the medial and lateral vestibular nuclei was seen with horizontal canal afferents compared to vertical canal fibers. Afferents innervating the utricle and saccule terminated generally in the lateral regions of all vestibular nuclei in areas that were separate from the projections of the semicircular canals. In addition, utricular fibers projected to regions in the vestibular nuclei that overlapped with the horizontal semicircular canal terminal fields, whereas saccular afferents projected to regions that received vertical canal fiber terminations. Lagenar

  9. The Influence of Pain on Masseter Spindle Afferent Discharge

    PubMed Central

    Capra, Norman F.; Hisley, Calvin K.; Masri, Radi M.

    2007-01-01

    Summary Muscle spindles provide proprioceptive feedback supporting normal patterns of motor activity and kinesthetic sensibility. During mastication, jaw muscle spindles play an important role in monitoring and regulating the chewing cycle and the bite forces generated during mastication. Both acute and chronic orofacial pain disorders are associated with changes in proprioceptive feedback and motor function. Experimental jaw muscle pain also alters the normal response of masseter spindle afferents to ramp and hold jaw movements [1]. It has been proposed that altered motor function and proprioceptive input results from group III muscle afferent modulation of the fusimotor system which alters spindle afferent sensitivity in limb muscles[2]. The response to nociceptive stimuli may enhance or reduce the response of spindle afferents to proprioceptive stimuli. Several experimental observations suggesting the possibility that a similar mechanism also functions in jaw muscles are presented in this report. First, evidence is provided to show that nociceptive stimulation of the masseter muscle primarily influences the amplitude sensitivity of spindle afferents with relatively little effect on the dynamic sensitivity [3]. Second, reversible inactivation of the caudal trigeminal nuclei attenuates the nociceptive modulation of spindle afferents. Finally, functionally identified gamma-motoneurons in the trigeminal motor nucleus are modulated by intramuscular injection with algesic substances. Taken together, these results suggest that pain-induced modulation of spindle afferent responses are mediated by small diameter muscle afferents and that this modulation is dependent, in part, on the relay of muscle nociceptive information from trigeminal subnucleus caudalis onto trigeminal gamma-motoneurons. The implication of these results will be considered in light of current theories on the relationship between jaw muscle pain and oral motor function. PMID:17126284

  10. Effect of erythrocyte aggregation at pathological levels on NO/O2 transport in small arterioles.

    PubMed

    Cho, Seungkwan; Namgung, Bumseok; Kim, Han Sung; Leo, Hwa Liang; Kim, Sangho

    2015-01-01

    This study examined the effects of red blood cell (RBC) aggregation at pathological levels on NO/O2 transport in small arterioles. Transient gas diffusion simulations were performed with in vivo cell-free layer (CFL) widths data obtained from arteriolar flows in the rat cremaster muscle. The CFL data were measured at physiological and pathological levels of aggregation under reduced flow conditions (pseudoshear rate = 31.4 ± 10.5 s-1). Our results showed that the mean peak NO concentration significantly decreased with increasing the aggregation level from non-aggregating to normal-aggregating (P < 0.05) and to hyper-aggregating (P < 0.01) conditions. In contrast, the partial O2 pressure (PO2) in pathological aggregating conditions significantly increased from those under non-aggregating (P < 0.001) and normal-aggregating (P < 0.05) conditions. Although the NO scavenging by RBCs could be impaired with a thicker CFL at higher levels of aggregation, the overall decrease in NO production due to reduction of wall shear stress with the thicker CFL dominantly limited the NO availability in tissue. On the other hand, the O2 availability in tissue increased due to the relatively high core hematocrit in the blood lumen with the thicker CFL.

  11. Arterioles supply oxygen to capillaries by diffusion as well as by convection.

    PubMed

    Ellsworth, M L; Pittman, R N

    1990-04-01

    In the early part of this century, August Krogh proposed a model of oxygen transport in capillaries that assumes that all oxygen is delivered to the capillaries by convection from small terminal arterioles and lost from these capillaries by diffusion. This model and its consequences have been used extensively to interpret whole organ oxygen transport data in terms of diffusion between capillaries and tissues and to relate changes in microvascular hemodynamics to alterations in oxygen transport. We evaluated the appropriateness of such extrapolation by measuring oxygen saturation at discrete locations along the lengths of individual capillaries in the hamster cheek pouch retractor muscle. Our results indicate that the amount of oxygen lost from individual capillaries can be markedly affected by the presence of larger microvessels that frequently cross the capillary path. These larger vessels act either as a diffusive supply of oxygen for the red blood cells within the capillary or as an additional sink for the oxygen depending on the direction of the oxygen tension gradient. This transfer of oxygen between larger microvessels and capillaries attenuates the importance of capillary hemodynamics in oxygen exchange. Therefore, conclusions about local oxygen exchange that utilize only hemodynamic data from whole organ or microvascular experiments and the Krogh model will generally be invalid and should be viewed with caution.

  12. Inherent rhythm of smooth muscle cells in rat mesenteric arterioles: An eigensystem formulation

    NASA Astrophysics Data System (ADS)

    Ho, I. Lin; Moshkforoush, Arash; Hong, Kwangseok; Meininger, Gerald A.; Hill, Michael A.; Tsoukias, Nikolaos M.; Kuo, Watson

    2016-04-01

    On the basis of experimental data and mathematical equations in the literature, we remodel the ionic dynamics of smooth muscle cells (SMCs) as an eigensystem formulation, which is valid for investigating finite variations of variables from the equilibrium such as in common experimental operations. This algorithm provides an alternate viewpoint from frequency-domain analysis and enables one to probe functionalities of SMCs' rhythm by means of a resonance-related mechanism. Numerical results show three types of calcium oscillations of SMCs in mesenteric arterioles: spontaneous calcium oscillation, agonist-dependent calcium oscillation, and agonist-dependent calcium spike. For simple single and double SMCs, we demonstrate properties of synchronization among complex signals related to calcium oscillations, and show different correlation relations between calcium and voltage signals for various synchronization and resonance conditions. For practical cell clusters, our analyses indicate that the rhythm of SMCs could (1) benefit enhancements of signal communications among remote cells, (2) respond to a significant calcium peaking against transient stimulations for triggering globally oscillating modes, and (3) characterize the globally oscillating modes via frog-leap (non-molecular-diffusion) calcium waves across inhomogeneous SMCs.

  13. Focal arteriolar insudation. A response of arterioles to chronic nonspecific irritation.

    PubMed Central

    Cuénoud, H. F.; Joris, I.; Langer, R. S.; Majno, G.

    1987-01-01

    The subcutaneous insertion of sterile, inert plastic pellets over the cremaster muscles of rats induces characteristic focal lesions of the arterioles at a distance from the pellets. These lesions appear with a delay of about 6 hours; by light microscopy they are characterized by a focal dilatation accompanied by endothelial damage and increased permeability. They are more severe if the pellets are loaded with histamine and are inhibited if the pellets are loaded with serotonin. Electron microscopy shows interendothelial gaps; the media is massively infiltrated with blood components and fibrin. The medial smooth muscle cells are stretched and at times necrotic; inflammatory cells are scarce. On the basis of these features the lesion was named focal arteriolar insudation (FAI). Although its pathogenesis is not yet clear, the data at hand suggest that it is caused by endogenous mediators affecting the smooth muscle cells and/or the endothelium. FAI appears to be a specific arteriolar response to chronic nonspecific irritation. Images Figure 7 Figure 2 Figure 1 Figure 3 Figure 6 Figure 8 PMID:3296773

  14. Propagated constriction in mouse pial arterioles: possible role of endothelium in transmitting the propagated response.

    PubMed

    Rosenblum, W I; Weinbrecht, P; Nelson, G H

    1990-01-01

    Two lines of evidence are presented demonstrating propagated constriction in mouse pial arterioles. First, a 2 second microapplication from a 6 micron pipette tip of approximately 12 nanoliters of BaCl2 or uridine triphosphate produced constrictions which spread to points 300 microns or more upstream from the point of application. Second, constrictions were elicited between 2 points of endothelial injury, each made with a focused laser beam 18 microns wide. A helium-neon laser was used in the presence of intravascular Evans blue. The constrictions were produced when a very brief exposure at a downstream site was followed by a more prolonged exposure at an upstream site 300 to 1100 microns from the downstream injury. In approximately half the cases the upstream damage elicited a local platelet aggregate. Therefore, vasoconstrictors released by aggregating platelets may have played a role in initiating constriction. Constriction was limited to the segment between the two endothelial injuries. The necessity for 2 injuries, rather than one, suggests that local losses of endothelium derived vasodilators also played a role in initiating constriction and/or permitting its propagation. Abrupt cessation of constriction at the sites of endothelial damage suggests that endothelium plays a role in propagation of constriction. Propagated constriction may play a role in amplifying the spasmotic effects of local subarachnoid hemorrhage or in the spread of constriction beyond local areas of reduced metabolic demand.

  15. The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-brain Barrier Permeability

    PubMed Central

    Cipolla, Marilyn J.; Godfrey, Julie A.; Wiegman, Marchien J.

    2009-01-01

    Objective We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability. Methods Female ovariectomized Sprague Dawley rats were replaced with estradiol (E2) and estriol (E3) (OVX+E; N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries. Results Ovariectomy increased myogenic tone in PA compared to CTL that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX+E was 44 ± 3% vs. 51 ± 1% and 54 ± 3% (p<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals, however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX and OVX+E was (ng/mL): 3.4 ± 1.2, 20.2 ± 5.3 (p<0.01 vs. CTL) and 6.15 ± 1.2 (n.s.). Conclusions These results suggest that estrogen replacement may not be beneficial for small vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it. PMID:19905968

  16. Effects of aging, TNF-α, and exercise training on angiotensin II-induced vasoconstriction of rat skeletal muscle arterioles.

    PubMed

    Park, Yoonjung; Prisby, Rhonda D; Behnke, Brad J; Dominguez, James M; Lesniewski, Lisa A; Donato, Anthony J; Muller-Delp, Judy; Delp, Michael D

    2012-10-01

    Skeletal muscle vascular resistance during physical exertion is higher with old age. The purpose of this study was to determine whether 1) aging enhances angiotensin II (ANG II)-induced vasoconstriction; 2) the proinflammatory cytokine tumor necrosis factor (TNF)-α contributes to alterations in ANG II-mediated vasoconstriction with aging; 3) exercise training attenuates putative age-associated increases in ANG II-mediated vasoconstriction; and 4) the mechanism(s) through which aging and exercise training alters ANG II-induced vasoconstriction in skeletal muscle arterioles. Male Fischer 344 rats were assigned to four groups: young sedentary (4 mo), old sedentary (24 mo), young trained, and old trained. In a separate group of young sedentary and old sedentary animals, a TNF type 1 receptor inhibitor was administered subcutaneously for 10 wk. First-order arterioles were isolated from soleus and gastrocnemius muscles for in vitro experimentation. Old age augmented ANG II-induced vasoconstriction in both soleus (young: 27 ± 3%; old: 38 ± 4%) and gastrocnemius (young: 42 ± 6%; old: 64 ± 9%) muscle arterioles; this augmented vasoconstriction was abolished with the removal of the endothelium, N(G)-nitro-l-arginine methyl ester, and chronic inhibition of TNF-α. In addition, exercise training ameliorated the age-induced increase in ANG II vasoconstriction. These findings demonstrate that old age enhances and exercise training diminishes ANG II-induced vasoconstrictor responses in skeletal muscle arterioles through an endothelium-dependent nitric oxide synthase signaling pathway. In addition, the enhancement of ANG II vasoconstriction with old age appears to be related to a proinflammatory state.

  17. Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles

    PubMed Central

    Spier, Scott A; Delp, Michael D; Meininger, Cynthia J; Donato, Anthony J; Ramsey, Michael W; Muller-Delp, Judy M

    2004-01-01

    Ageing reduces endothelium-dependent vasodilatation in humans and animals, and in humans, exercise training reverses the ageing-associated reduction in endothelium-dependent vasodilatation. The purpose of this study was to determine the mechanism(s) by which 10–12 weeks of treadmill exercise enhances endothelium-dependent vasodilatation in muscles of differing fibre composition from young and old rats. Three- and 22-month-old male Fischer 344 rats were assigned to young sedentary, young exercise-trained, old sedentary, or old exercise-trained groups. Arterioles were isolated from the soleus and gastrocnemius muscles; luminal diameter changes were determined in response to the endothelium-dependent vasodilator acetylcholine (ACh, 10−9–10−4 mol l−1) alone and in the presence of the nitric oxide synthase (NOS) inhibitor l-NAME (10−5 mol l−1) or the combination of l-NAME and the cyclooxygenase inhibitor indomethacin (10−5 mol l−1). Training ameliorated the ageing-induced reduction in endothelium-dependent vasodilatation in soleus muscle arterioles. Treatment with l-NAME alone and in combination with indomethacin abolished differences in ACh vasodilatation occurring with ageing and training. Expression of endothelial NOS (eNOS) mRNA in soleus arterioles was unaltered by ageing, whereas eNOS protein was increased with age; training elevated both eNOS mRNA and protein. In gastrocnemius muscle arterioles, ageing did not alter maximal vasodilatation, but ageing and training increased maximal arteriolar diameter. These results demonstrate that ageing-induced reductions and training-induced enhancement of endothelial vasodilatation both occur through the nitric oxide signalling mechanism in highly oxidative skeletal muscle, but ageing and training do not appear to act on the same portion of the signalling cascade. PMID:15004211

  18. Mast cells drive mesenteric afferent signalling during acute intestinal ischaemia.

    PubMed

    Jiang, Wen; Kirkup, Anthony J; Grundy, David

    2011-08-01

    Acute intestinal ischaemia stimulates visceral afferent nerves but the mechanisms responsible for this excitation are not fully understood. Mast cells may participate in this process as they are known to signal to mesenteric afferents during intestinal anaphylaxis and contribute to early inflammation and neuronal damage in response to cerebral ischaemia. We therefore hypothesised that mast cells are early responders to acute intestinal ischaemia and their activation initiates rapid signalling to the CNS via the excitation of mesenteric afferents. Primary afferent firing was recorded from a mesenteric nerve bundle supplying a segment of jejunum in anaesthetized adult rats. Acute focal ischaemia was produced by clamping theme senteric vessels for 8 min, and reperfusion followed removal of the vessel clip. Two episodes of ischaemia–reperfusion (I–R) separated by a 30 min interval were performed. Drugs or their vehicles were administered 10 min before the 2nd I–R episode. Ischaemia caused a reproducible, intense and biphasic afferent firing that was temporally dissociated from the concomitantly triggered complex pattern of intestinal motor activity. The L-type calcium channel blocker, nifedipine, significantly attenuated this afferent firing by a mechanism independent of its action on intestinal tone. Ischaemia-induced afferent firing was also abrogated by the mast cell stabilizer, doxantrazole, and the H1 histamine receptor antagonist, pyrilamine. In contrast, the nicotinic receptor antagonist, hexamethonium, and the N-type calcium channel toxin, ω-conotoxin GVIA, each reduced the ischaemia-evoked motor inhibition but not the concurrent afferent discharge. Similarly, the cyclooxygenase inhibitor, naproxen, had no effect on the ischaemic afferent response but reduced the intestinal tone shortly from the onset of ischaemia to the early period of reperfusion. These data support a critical role for mast cell-derived histamine in the direct chemoexcitation of

  19. Afferent innervation of the utricular macula in pigeons

    NASA Technical Reports Server (NTRS)

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  20. Afferent innervation of the utricular macula in pigeons.

    PubMed

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J David

    2003-03-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  1. Afferent innervation of the utricular macula in pigeons

    NASA Technical Reports Server (NTRS)

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  2. Anti-CD31 delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles.

    PubMed Central

    Rosenblum, W. I.; Murata, S.; Nelson, G. H.; Werner, P. K.; Ranken, R.; Harmon, R. C.

    1994-01-01

    The arterioles on the surface of the mouse brain (pial arterioles) were observed by in vivo microscopy. A focus of minor endothelial damage was produced in a single pial arteriole in each mouse by briefly exposing the site to a helium neon laser after an intravenous injection of Evans blue. Mice were injected 10 minutes before injury with a monoclonal antibody (MAb) to mouse CD31, also known as platelet endothelial cell adhesion molecule. This treatment doubled (P < .01) the time required for the laser to produce a recognizable platelet aggregate. In additional experiments, an MAb to mouse CD61 and an MAb to mouse intercellular adhesion molecule 1 had no effect. The data support previous observations indicating that platelet adhesion/aggregation in this model is induced by endothelial injury without exposure of basal lamina. The data are consistent with the hypothesis that the endothelial injury exposes or activates a platelet endothelial cell adhesion molecule on the endothelium which is blocked by the MAb directed against CD31. This may be the first demonstration of an effect of an anti-platelet endothelial cell adhesion molecule on platelet endothelial cell adhesion molecule on platelet adhesion/aggregation in vivo. PMID:8030753

  3. Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

    PubMed Central

    Wang, Ping M.; Kachel, Diane L.; Cesta, Mark F.; Martin, William J.

    2011-01-01

    During acute lung injury and repair, leukocytes are thought to enter the lung primarily across alveolar capillaries and postcapillary venules. We hypothesized that leukocytes also migrate across pulmonary arterioles and venules, which serve as alternative sites for leukocyte influx into the lung during acute lung injury and repair. Lung sections from C57BL/6J mice up to 14 days after intratracheal bleomycin (3.33 U/kg) or saline instillation were assessed by light, fluorescence, confocal, and transmission electron microscopy for evidence of inflammatory cell sequestration and transmigration at these sites. After bleomycin treatment, large numbers of leukocytes (including neutrophils, eosinophils, and monocytes) were present in the vascular lumina and in perivascular interstitia of pulmonary arterioles and venules, as well as within the vascular walls. Leukocytes were observed within well-defined pathways in arteriolar walls and much less structured pathways in venular walls, apparently in the process of transmigration. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were expressed at sites of leukocyte interaction with the luminal surface, especially in arterioles. Leukocytes appeared to exit from the vessels near collagen fibers into the perivascular interstitium. Results indicate that leukocytes can directly migrate across arteriolar and venular walls into the perivascular interstitium, which may represent an important but under-recognized pathway for leukocyte influx into the lung during injury and repair. PMID:21641381

  4. Noradrenaline stimulation of the phosphoinositide system: evidence for a novel hydrophobic inositol-containing compound in resistance arterioles.

    PubMed Central

    Ollerenshaw, J. D.; Heagerty, A. M.; Swales, J. D.

    1988-01-01

    1. Five inositol phosphates were extracted from adult rat resistance arterioles and separated by ion-exchange high performance liquid chromatography. 2. By use of this technique, inositol phosphates liberated were identified as inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. Stimulation of phosphoinositide hydrolysis with noradrenaline produced increases in inositol phosphate production. 3. Three inositol-containing phospholipids extracted from resistance arterioles were measured as their glycerol esters following deacylation, thereby permitting an analysis of both membrane and cytosolic components of the phosphoinositide signalling system. 4. A substantial agonist-sensitive pool of a previously undescribed inositol but not glycerol-containing lipid extract component was also identified in this tissue. 5. These experiments for the first time allow a precise description of phosphoinositide metabolism in resting and agonist-stimulated resistance arterioles and provide data on a novel compound possibly similar to that recently described in other tissues. PMID:2840158

  5. Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BKCa channels in collateral-dependent porcine coronary arterioles

    PubMed Central

    Xie, Wei; Parker, Janet L.; Heaps, Cristine L.

    2012-01-01

    Objective Test the hypothesis that exercise training increases the contribution of large-conductance, Ca2+-dependent K+ (BKCa) channels to endothelium-mediated dilation in coronary arterioles from collateral-dependent myocardial regions of chronically occluded pig hearts and may function downstream of H2O2. Methods An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 wk) regimens. Results Exercise training significantly enhanced bradykinin-mediated dilation in collateral-dependent arterioles (~125 μm diameter) compared with sedentary pigs. The BKCa-channel blocker, iberiotoxin alone or in combination with the H2O2 scavenger, polyethylene glycol catalase, reversed exercise training-enhanced dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K+ currents (i.e., BKCa-channel currents) were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups. Conclusions These data provide evidence that BKCa-channel activity contributes to exercise training-enhanced endothelium-dependent dilation in collateral-dependent coronary arterioles despite no change in smooth muscle BKCa-channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BKCa channels, is enhanced by exercise training in collateral-dependent arterioles and suggest a potential role for H2O2 as the mediator. PMID:23002811

  6. Contraction-evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre-diabetic mice.

    PubMed

    Novielli, N M; Jackson, D N

    2014-06-01

    To investigate the effects of pre-diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre-diabetes compromises contraction-evoked vasodilation of branching second-order (2A), third-order (3A) and fourth-order (4A) arterioles, where distal arterioles would be affected the greatest. Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre-diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice. Baseline diameter and blood flow were similar between groups (2A: ~20 μm, 3A: ~14 μm and 4A: ~8 μm; 2A: ~1 nL s(-1) and 3A: ~0.5 nL s(-1) ). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid-onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of ROV was up to 2-fold greater at distal arterioles (3A and 4A) vs. proximal arterioles (2A) in CTRL; however, in PD, ROV of only 4A was greater than 2A (P < 0.05). Rhythmic contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of vasodilatory responses to rhythmic contraction was also up to 2.5-fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD. Arteriolar dysregulation in pre-diabetes causes deficits in contraction-evoked dilation and blood flow, where greatest deficits occur at distal arterioles. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Patterns of connectivity of spinal interneurons with single muscle afferents.

    PubMed

    Quevedo, J; Eguibar, J R; Lomeli, J; Rudomin, P

    1997-07-01

    A technique was developed to measure, in the anesthetized and paralyzed cat under artificial ventilation, changes of excitability to intraspinal stimulation simultaneously in two different afferent fibers or in two collaterals of the same afferent fiber. Intraspinal stimulation reduced the threshold of single muscle afferent fibers ending in the intermediate nucleus. This effect was seen with strengths below those required to activate the afferent fiber tested (1.5-12 microA), occurred at a short latency (1.5-2.0 ms), reached a maximum between 15 and 30 ms, and lasted up to 100 ms. The effects produced by graded stimulation applied at the shortest conditioning-testing stimulus time intervals increased by fixed steps, suggesting recruitment of discrete elements, most likely of last-order interneurons mediating primary afferent depolarization (PAD). The short-latency increases in excitability produced by the weakest effective intraspinal stimuli were usually detected only in the collateral closest to the stimulating micropipette, indicating that the stimulated interneurons mediating PAD have spatially restricted actions. The short-latency PAD produced by intraspinal stimuli, as well as the PAD produced by stimulation of the posterior biceps and semitendinosus (PBSt) nerve or by stimulation of the bulbar reticular formation (RF), was depressed 19-30 min after the i.v. injection of 0.5 mg/kg of picrotoxin, suggesting that all these effects were mediated by GABAergic mechanisms. The PAD elicited by stimulation of muscle and/or cutaneous nerves was depressed following the i.v. injection of (-)-baclofen, whereas the PAD elicited in the same collateral by stimulation of the RF was baclofen-resistant. The short-latency PAD produced by intraspinal stimulation was not always depressed by i.v. injections of (-)-baclofen. Baclofen-sensitive and baclofen-resistant monosynaptic PADs could be produced in different collaterals of the same afferent fiber. The results suggest that

  8. Gut vagal afferents differentially modulate innate anxiety and learned fear.

    PubMed

    Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

    2014-05-21

    Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior.

  9. Rapid vasodilation in isolated skeletal muscle arterioles: impact of branch order.

    PubMed

    Roseguini, Bruno T; Davis, Michael J; Harold Laughlin, M

    2010-02-01

    We tested the hypothesis that segmental differences in the responsiveness and time course of vasodilation to metabolic signals putatively involved in rapid onset vasodilation (ROV) at the start of exercise exist within the skeletal muscle vasculature. Cannulated first-order (1As) and third-order arterioles (3As) of the rat gastrocnemius (G) muscle were exposed to cumulative doses of KCl, acetylcholine (Ach), or adenosine (Ado). In addition, time course and magnitude of vasodilation to localized application of these agonists were determined. 1As and 3As dilated similarly to incremental doses of the agonists. Continuous monitoring of internal diameter revealed a fast and transient dilatory response to microinjections of the agonists, with an average time delay (TD) before the onset of vasodilation of 2.8 +/- 0.2 seconds (1As: 3.0 +/- 0.3 seconds and 3As: 2.6 +/- 0.3 seconds) and time-to-peak (TP) of 8.2 +/- 0.7 seconds (1As: 10.3 +/- 1 seconds and 3As:5.7 +/- 0.5 seconds). No significant differences were detected for all parameters between 1As and 3As for KCl or Ado application, while 1As had a significantly longer TP and greater peak dilation than 3As to Ach. These findings demonstrate that 1As and 3As from the rat G muscle appear to have similar responsiveness to vasoactive agonists. Furthermore, the average TD before vasodilation supports a role for metabolic signals as contributors to the ROV.

  10. Relationships between retinal arteriole anatomy and aortic geometry and function and peripheral resistance in hypertensives.

    PubMed

    Rosenbaum, David; Kachenoura, Nadjia; Koch, Edouard; Paques, Michel; Cluzel, Philippe; Redheuil, Alban; Girerd, Xavier

    2016-07-01

    Microvascular remodeling and large artery stiffness are key determinants of cardiovascular hemodynamics and can now be studied with new non-invasive methods. Our objective was to study the relationships between retinal arteriole anatomy and aortic geometry and function and peripheral resistance (total peripheral resistance (TPR)) in hypertensives. In 80 subjects (age 52±13 years; 53% males; including 23 normotensives and 57 hypertensives, among which 29 were uncontrolled hypertensives), we used: (1) the new non-invasive RTX1 adaptive optics (AO) camera (Imagine Eyes, Orsay, France) to measure the wall-to-lumen ratio (WLR) on retinal microvasculature; (2) cardiovascular magnetic resonance (CMR) imaging to assess aortic stiffness, geometry and cardiac output; and (3) the validated SphymoCor Xcel device to measure central blood pressure (BP) and carotido-femoral pulse wave velocity (Cf-PWV). TPR was calculated as the central mean BP/cardiac output ratio. WLR and TPR were significantly higher and aortic distensibility was significantly lower in hypertensives. Aortic dilation and arch elongation were found in uncontrolled hypertensives. In the univariate analysis, WLR was positively correlated with central BP (P<0.001), TPR (P<0.001) and Cf-PWV (P<0.05), and it was negatively correlated with aortic distensibility (P=0.003); however, it was not correlated with age or cardiovascular risk factors. The multivariate analysis indicated that WLR was associated with TPR (P=0.002) independent of age, BMI, gender, antihypertensive treatments, aortic diameter and central SBP. As expected, age was the major correlate of ascending aorta distensibility and Cf-PWV. New non-invasive vascular imaging methods are complementary for the detection of the deleterious effects of aging or high BP on large and small arteries. AO examination could represent a useful tool for the study and follow-up of microvasculature anatomical changes.

  11. Flow structures and red blood cell dynamics in arteriole of dilated or constricted cross section.

    PubMed

    Gambaruto, Alberto M

    2016-07-26

    Vessel with 'circular' or 'star-shaped' cross sections are studied, representing respectively dilated or constricted cases where endothelial cells smoothly line or bulge into the lumen. Computational haemodynamics simulations are carried out on idealised periodic arteriole-sized vessels, with red blood cell 'tube' hematocrit value=24%. A further simulation of a single red blood cell serves for comparison purposes. The bulk motion of the red blood cells reproduces well-known effects, including the presence of a cell-free layer and the apparent shear-thinning non-Newtonian rheology. The velocity flow field is analysed in a Lagrangian reference frame, relative to any given red blood cell, hence removing the bulk coaxial motion and highlighting instead the complex secondary flow patterns. An aggregate formation becomes apparent, continuously rearranging and dynamic, brought about by the inter-cellular fluid mechanics interactions and the deformability properties of the cells. The secondary flow field induces a vacillating radial migration of the red blood cells. At different radial locations, the red blood cells express different residence times, orientation and shape. The shear stresses exerted by the flow on the vessel wall are influenced by the motion of red blood cells, despite the presence of the cell-free layer. Spatial (and temporal) variations of wall shear stress patters are observed, especially for the 'circular' vessel. The 'star-shaped' vessel bears considerable stress at the protruding endothelial cell crests, where the stress vectors are coaxially aligned. The bulging endothelial cells hence regularise the transmission of stresses on the vessel wall.

  12. Intraluminal pressure stimulates MAPK phosphorylation in arterioles: temporal dissociation from myogenic contractile response.

    PubMed

    Spurrell, Brian E; Murphy, Timothy V; Hill, Michael A

    2003-10-01

    Members of the MAPK family of enzymes, p42/44 and p38, have been implicated in both the regulation of contractile function and growth responses in vascular smooth muscle. We determined whether such kinases are activated during the arteriolar myogenic response after increases in intraluminal pressure. Particular emphasis was placed on temporal aspects of activation to determine whether such phosphorylation events parallel the known time course for myogenic contraction. Experiments used single cannulated arterioles isolated from the cremaster muscle of rats with some vessels loaded with the fluorescent Ca2+-sensitive dye fura 2 (2 microM). The p42/44 inhibitor PD-98059 (50 microM) caused vasodilation but did not prevent pressure-induced myogenic constriction. The vasodilator response was accompanied by decreased smooth muscle intracellular Ca2+. Western blotting revealed a significant increase in the level of phosphorylation of p42/44 15 min after the application of a 30- to 100-mmHg pressure step. Phosphorylation of p42/44 was a late event that appeared to be temporally dissociated from contraction, which was complete within 1-5 min. EGF (80 nM) caused marked phosphorylation of p42/44 but only acted as a weak vasoconstrictor. The p38 inhibitor SB-203580 (10 microM) did not alter baseline diameter, nor did it prevent myogenic vasoconstriction. Consistent with these observations, SB-203580 did not cause a measurable change in intracellular Ca2+. The results demonstrate activation of the p42/44 class of MAPK resulting from increased transmural pressure. Such activation is, however, dissociated from the acute pressure-induced vasoconstrictor response in terms of time course and may represent the activation of compensatory, but parallel, pathways, including those related to growth and remodeling.

  13. Laparoscopy in Afferent Loop Obstruction Presenting as Acute Pancreatitis

    PubMed Central

    Pettinato, Giovanna; Romessis, Matheos; Ferrari Bravo, Andrea; Barozzi, Geraldine; Giovanetti, Maurizio

    2006-01-01

    Background: We describe an afferent loop obstruction caused by an adhesion band in a case of distal gastrectomy with Roux-en-Y end-to-side jejunal anastomosis for cancer. Methods: An initial clinical presentation of acute pancreatitis was ruled out by a computed tomography scan, which revealed intestinal obstruction; it was then confirmed on laparoscopy. Definitive treatment was laparoscopic adhesiolysis. A complete review of the literature concerning afferent loop obstructions is presented. Results: The treatment was successful, with minimal postoperative pain, and the 5-day hospital stay was uncomplicated. The patient remains asymptomatic at 1-year follow-up. Conclusions: The authors advocate minimally invasive surgery as a complete diagnostic and therapeutic alternative to emergency laparotomy in cases where afferent loop syndrome is suspected, and acknowledge that prompt surgery has a higher rate of success and reduces operative morbidity and mortality. PMID:16882437

  14. The role of gastrointestinal vagal afferent fibres in obesity

    PubMed Central

    Kentish, Stephen J; Page, Amanda J

    2015-01-01

    Gastrointestinal (GI) vagal afferents are a key mediatory of food intake. Through a balance of responses to chemical and mechanical stimuli food intake can be tightly controlled via the ascending satiety signals initiated in the GI tract. However, vagal responses to both mechanical and chemical stimuli are modified in diet-induced obesity (DIO). Much of the research to date whilst in relatively isolated/controlled circumstances indicates a shift between a balance of orexigenic and anorexigenic vagal signals to blunted anorexigenic and potentiated orexigenic capacity. Although the mechanism responsible for the DIO shift in GI vagal afferent signalling is unknown, one possible contributing factor is the gut microbiota. Nevertheless, whatever the mechanism, the observed changes in gastrointestinal vagal afferent signalling may underlie the pathophysiological changes in food consumption that are pivotal for the development and maintenance of obesity. PMID:25433079

  15. Determinants of Spatial and Temporal Coding by Semicircular Canal Afferents

    PubMed Central

    Highstein, Stephen M.; Rabbitt, Richard D.; Holstein, Gay R.; Boyle, Richard D.

    2010-01-01

    The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components—one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below. PMID:15845995

  16. Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis.

    PubMed

    Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A

    2010-09-01

    Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.

  17. Nociceptive primary afferents: they have a mind of their own

    PubMed Central

    Carlton, Susan M

    2014-01-01

    Nociceptive primary afferents have three surprising properties: they are highly complex in their expression of neurotransmitters and receptors and most probably participate in autocrine and paracrine interactions; they are capable of exerting tonic and activity-dependent inhibitory control over incoming nociceptive input; they can generate signals in the form of dorsal root reflexes that are transmitted antidromically out to the periphery and these signals can result in neurogenic inflammation in the innervated tissue. Thus, nociceptive primary afferents are highly complicated structures, capable of modifying input before it is ever transmitted to the central nervous system and capable of altering the tissue they innervate. PMID:24879874

  18. Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles.

    PubMed

    Westcott, Erika B; Jackson, William F

    2011-05-01

    The roles played by ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP₃Rs) in vascular smooth muscle in the microcirculation remain unclear. Therefore, the function of both RyRs and IP₃Rs in Ca(²+) signals and myogenic tone in hamster cremaster muscle feed arteries and downstream arterioles were assessed using confocal imaging and pressure myography. Feed artery vascular smooth muscle displayed Ca(²+) sparks and Ca(²+) waves, which were inhibited by the RyR antagonists ryanodine (10 μM) or tetracaine (100 μM). Despite the inhibition of sparks and waves, ryanodine or tetracaine increased global intracellular Ca(²+) and constricted the arteries. The blockade of IP₃Rs with xestospongin D (5 μM) or 2-aminoethoxydiphenyl borate (100 μM) or the inhibition of phospholipase C using U-73122 (10 μM) also attenuated Ca(2+) waves without affecting Ca(²+) sparks. Importantly, the IP₃Rs and phospholipase C antagonists decreased global intracellular Ca(2+) and dilated the arteries. In contrast, cremaster arterioles displayed only Ca(²+) waves: Ca(²+) sparks were not observed, and neither ryanodine (10-50 μM) nor tetracaine (100 μM) affected either Ca(²+) signals or arteriolar tone despite the presence of functional RyRs as assessed by responses to the RyR agonist caffeine (10 mM). As in feed arteries, arteriolar Ca(²+) waves were attenuated by xestospongin D (5 μM), 2-aminoethoxydiphenyl borate (100 μM), and U-73122 (10 μM), accompanied by decreased global intracellular Ca(²+) and vasodilation. These findings highlight the contrasting roles played by RyRs and IP₃Rs in Ca(²+) signals and myogenic tone in feed arteries and demonstrate important differences in the function of RyRs between feed arteries and downstream arterioles.

  19. Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles

    PubMed Central

    Westcott, Erika B.

    2011-01-01

    The roles played by ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in vascular smooth muscle in the microcirculation remain unclear. Therefore, the function of both RyRs and IP3Rs in Ca2+ signals and myogenic tone in hamster cremaster muscle feed arteries and downstream arterioles were assessed using confocal imaging and pressure myography. Feed artery vascular smooth muscle displayed Ca2+ sparks and Ca2+ waves, which were inhibited by the RyR antagonists ryanodine (10 μM) or tetracaine (100 μM). Despite the inhibition of sparks and waves, ryanodine or tetracaine increased global intracellular Ca2+ and constricted the arteries. The blockade of IP3Rs with xestospongin D (5 μM) or 2-aminoethoxydiphenyl borate (100 μM) or the inhibition of phospholipase C using U-73122 (10 μM) also attenuated Ca2+ waves without affecting Ca2+ sparks. Importantly, the IP3Rs and phospholipase C antagonists decreased global intracellular Ca2+ and dilated the arteries. In contrast, cremaster arterioles displayed only Ca2+ waves: Ca2+ sparks were not observed, and neither ryanodine (10–50 μM) nor tetracaine (100 μM) affected either Ca2+ signals or arteriolar tone despite the presence of functional RyRs as assessed by responses to the RyR agonist caffeine (10 mM). As in feed arteries, arteriolar Ca2+ waves were attenuated by xestospongin D (5 μM), 2-aminoethoxydiphenyl borate (100 μM), and U-73122 (10 μM), accompanied by decreased global intracellular Ca2+ and vasodilation. These findings highlight the contrasting roles played by RyRs and IP3Rs in Ca2+ signals and myogenic tone in feed arteries and demonstrate important differences in the function of RyRs between feed arteries and downstream arterioles. PMID:21357503

  20. Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

    PubMed Central

    Sindler, Amy L.; Reyes, Rafael; Chen, Bei; Ghosh, Payal; Gurovich, Alvaro N.; Kang, Lori S.; Cardounel, Arturo J.; Delp, Michael D.

    2013-01-01

    Exercise training ameliorates age-related impairments in endothelium-dependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise training-induced enhancement of endothelial function occurs, in part, through an increase in ROS signaling. PMID:23288555

  1. Reactive oxygen species facilitate the EDH response in arterioles by potentiating intracellular endothelial Ca(2+) release.

    PubMed

    Chidgey, James; Fraser, Paul A; Aaronson, Philip I

    2016-08-01

    There is abundant evidence that H2O2 can act as an endothelium-derived hyperpolarizing factor in the resistance vasculature. However, whilst scavenging H2O2 can abolish endothelial dependent hyperpolarization (EDH) and the associated vascular relaxation in some arteries, EDH-dependent vasorelaxation can often be mimicked only by using relatively high concentrations of H2O2. We have examined the role of H2O2 in EDH-dependent vasodilatation by simultaneously measuring vascular diameter and changes in endothelial cell (EC) [Ca(2+)]i during the application of H2O2 or carbachol, which triggers EDH. Carbachol (10µM) induced dilatation of phenylephrine-preconstricted rat cremaster arterioles was largely (73%) preserved in the presence of indomethacin (3µM) and l-NAME (300µM). This residual NO- and prostacyclin-independent dilatation was reduced by 89% upon addition of apamin (0.5µM) and TRAM-34 (10µM), and by 74% when an extracellular ROS scavenging mixture of SOD and catalase (S&C; 100Uml(-1) each) was present. S&C also reduced the carbachol-induced EC [Ca(2+)]i increase by 74%. When applied in Ca(2+)-free external medium, carbachol caused a transient increase in EC [Ca(2+)]i. This was reduced by catalase, and was enhanced when 1µM H2O2 was present in the bath. H2O2 -induced dilatation, which occurred only at concentrations ≥100µM, was reduced by a blocking antibody to TRPM2, which had no effect on carbachol-induced responses. Similarly, iberotoxin and Rp-8bromo cGMP reduced the vasodilatation induced by H2O2, but not by carbachol. Inhibiting PLC, PLA2 or CYP450 2C9 each greatly reduced the carbachol-induced increase in EC [Ca(2+)]i and vasodilatation, but adding 10µM H2O2 during PLA2 or CYP450 2C9 inhibition completely restored both responses. The nature of the effective ROS species was investigated by using Fe(2+) chelators to block the formation of ∙OH. A cell permeant chelator was able to inhibit EC Ca(2+) store release, but cell impermeant chelators

  2. Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels.

    PubMed

    Nagaoka, Taiji; Hein, Travis W; Yoshida, Akitoshi; Kuo, Lih

    2007-09-01

    Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrol-induced diameter changes were recorded by videomicroscopic techniques. Retinal arterioles (65 +/- 3 microm) dilated dose dependently in response to resveratrol (1-50 microM). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N(G)-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K(+) channel blocker, tetraethylammonium (TEA), and a large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K(+) channels and voltage-gated K(+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol. Resveratrol elicits endothelium-dependent and -independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase (NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BK(Ca) channels in smooth

  3. Sensations evoked by microstimulation of single mechanoreceptive afferents innervating the human face and mouth.

    PubMed

    Trulsson, M; Essick, G K

    2010-04-01

    Intraneural microneurography and microstimulation were performed on single afferent axons in the inferior alveolar and lingual nerves innervating the face, teeth, labial, or oral mucosa. Using natural mechanical stimuli, 35 single mechanoreceptive afferents were characterized with respect to unit type [fast adapting type I (FA I), FA hair, slowly adapting type I and II (SA I and SA II), periodontal, and deep tongue units] as well as size and shape of the receptive field. All afferents were subsequently microstimulated with pulse trains at 30 Hz lasting 1.0 s. Afferents recordings whose were stable thereafter were also tested with single pulses and pulse trains at 5 and 60 Hz. The results revealed that electrical stimulation of single FA I, FA hair, and SA I afferents from the orofacial region can evoke a percept that is spatially matched to the afferent's receptive field and consistent with the afferent's response properties as observed on natural mechanical stimulation. Stimulation of FA afferents typically evoked sensations that were vibratory in nature; whereas those of SA I afferents were felt as constant pressure. These afferents terminate superficially in the orofacial tissues and seem to have a particularly powerful access to perceptual levels. In contrast, microstimulation of single periodontal, SA II, and deep tongue afferents failed to evoke a sensation that matched the receptive field of the afferent. These afferents terminate more deeply in the tissues, are often active in the absence of external stimulation, and probably access perceptual levels only when multiple afferents are stimulated. It is suggested that the spontaneously active afferents that monitor tension in collagen fibers (SA II and periodontal afferents) may have the role to register the mechanical state of the soft tissues, which has been hypothesized to help maintain the body's representation in the central somatosensory system.

  4. Changes in monkey horizontal semicircular canal afferent responses after spaceflight

    NASA Technical Reports Server (NTRS)

    Correia, M. J.; Perachio, A. A.; Dickman, J. D.; Kozlovskaia, I. B.; Sirota, M. G.; Iakushin, S. B.; Beloozerova, I. N.

    1992-01-01

    Extracellular responses from single horizontal semicircular canal afferents in two rhesus monkeys were studied after recovery from a 14-day biosatellite (Cosmos 2044) orbital spaceflight. On the 1st postflight day, the mean gain for 9 different horizontal canal afferents, tested using one or several different passive yaw rotation waveforms, was nearly twice that for 20 horizontal canal afferents similarly tested during preflight and postflight control studies. Adaptation of the afferent response to passive yaw rotation on the 1st postflight day was also greater. These results suggest that at least one component of the vestibular end organ (the semicircular canals) is transiently modified after exposure to 14 days of microgravity. It is unclear whether the changes are secondary to other effects of microgravity, such as calcium loss, or an adaptive response. If the response is adaptive, then this report is the first evidence that the response of the vestibular end organ may be modified (presumably by the central nervous system via efferent connections) after prolonged unusual vestibular stimulation. If this is the case, the sites of plasticity of vestibular responses may not be exclusively within central nervous system vestibular structures, as previously believed.

  5. Gut chemosensing: interactions between gut endocrine cells and visceral afferents.

    PubMed

    Raybould, Helen E

    2010-02-16

    Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on a new data on endocrine cells in chemosensing in the GI tract, in particular on new findings on glucose-sensing by gut EEC cells and the importance of incretin peptides and vagal afferents in glucose homeostasis, on the role of G protein coupled receptors in gut chemosensing, and on the possibility that gut endocrine cells may be involved in the detection of a luminal constituent other than nutrients, the microbiota. The role of vagal afferent pathways as a downstream target of EEC cell products will be considered and, in particular, exciting new data on the plasticity of the vagal afferent pathway with respect to expression of receptors for GI hormones and how this may play a role in energy homeostasis will also be discussed.

  6. Tactile afferents encode grip safety before slip for different frictions.

    PubMed

    Khamis, Heba A; Redmond, Stephen J; Macefield, Vaughan G; Birznieks, Ingvars

    2014-01-01

    Adjustments to frictional forces are crucial to maintain a safe grip during precision object handling in both humans and robotic manipulators. The aim of this work was to investigate whether a population of human tactile afferents can provide information about the current tangential/normal force ratio expressed as the percentage of the critical load capacity - the tangential/normal force ratio at which the object would slip. A smooth stimulation surface was tested on the fingertip under three frictional conditions, with a 4 N normal force and a tangential force generated by motion in the ulnar or distal direction at a fixed speed. During stimulation, the responses of 29 afferents (12 SA-I, 2 SA-II, 12 FA-I, 3 FA-II) were recorded. A multiple regression model was trained and tested using cross-validation to estimate the percentage of the critical load capacity in real-time as the tangential force increased. The features for the model were the number of spikes from each afferent in windows of fixed length (50, 100 or 200 ms) around points spanning the range from 50% to 100% of the critical load capacity, in 5% increments. The mean regression estimate error was less than 1% of the critical load capacity with a standard deviation between 5% and 10%. A larger number of afferents is expected to improve the estimate error. This work is important for understanding human dexterous manipulation and inspiring improvements in robotic grippers and prostheses.

  7. [Characteristics of unitary afferent discharges of neuromuscular spindles in man].

    PubMed

    Mano, T; Takagi, S; Mitarai, G

    1976-01-01

    The primary ending of muscle spindle in man shows a dynamic and static sensitivity to stretch, but the dynamic and vibratory sensitivities as well as conduction velocity of the afferent fibres seem to be relatively low in comparison to those described in the cat.

  8. Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

    PubMed Central

    Oliva, Idaira; Wanat, Matthew J.

    2016-01-01

    Drug-related behaviors in both humans and rodents are commonly thought to arise from aberrant learning processes. Preclinical studies demonstrate that the acquisition and expression of many drug-dependent behaviors involves the ventral tegmental area (VTA), a midbrain structure comprised of dopamine, GABA, and glutamate neurons. Drug experience alters the excitatory and inhibitory synaptic input onto VTA dopamine neurons, suggesting a critical role for VTA afferents in mediating the effects of drugs. In this review, we present evidence implicating the VTA in drug-related behaviors, highlight the diversity of neuronal populations in the VTA, and discuss the behavioral effects of selectively manipulating VTA afferents. Future experiments are needed to determine which VTA afferents and what neuronal populations in the VTA mediate specific drug-dependent behaviors. Further studies are also necessary for identifying the afferent-specific synaptic alterations onto dopamine and non-dopamine neurons in the VTA following drug administration. The identification of neural circuits and adaptations involved with drug-dependent behaviors can highlight potential neural targets for pharmacological and deep brain stimulation interventions to treat substance abuse disorders. PMID:27014097

  9. Regenerating sprouts of axotomized cat muscle afferents express characteristic firing patterns to mechanical stimulation.

    PubMed

    Johnson, R D; Munson, J B

    1991-12-01

    1. In cats, we studied the physiological properties of regenerating sprouts of muscle afferent fibers and compared them with sprouts from cutaneous afferent fibers. 2. Muscle nerves to the triceps surae and cutaneous sural nerves were axotomized in the popliteal fossa, and the proximal ends were inserted into nerve cuffs. Six days later, we recorded action potentials from single Groups I and II muscle and mostly Group II cutaneous afferents driven by mechanostimulation of the cuff. 3. Most muscle afferent sprouts (91%) had a regular slowly adapting discharge in response to sustained mechanical displacement of the cuff, particularly to sustained stretch stimuli, whereas most cutaneous afferents (92%) did not. Muscle afferents were more likely to have a spontaneous discharge and afterdischarge. 4. Group II muscle afferent sprouts had lower stretch thresholds and a higher incidence of spontaneous discharge compared with Group I fiber sprouts, whereas Group I fibers had a higher incidence of high-frequency afterdischarge to mechanical stimuli. 5. We conclude that, 6 days after axotomy, regenerating sprouts of muscle afferents, particularly Group II afferents, have become mechanosensitive in the absence of a receptor target and exhibit physiological properties similar to those found when innervating their native muscle but significantly different from sprouts of cutaneous afferents. Expression of these native muscle afferent firing patterns after the inappropriate reinnervation of hairy skin may be due to inherent properties of the muscle afferent fiber.

  10. Effects of antidromic discharges in crayfish primary afferents.

    PubMed

    Cattaert, Daniel; Bévengut, Michelle

    2002-10-01

    Contrary to orthodromic spikes that are generated in sensory organs and conveyed to CNS, antidromic spikes are generated in the axon terminals of the sensory neurons within the CNS and are conveyed to the peripheral sensory organ. Antidromic discharges are observed in primary afferent neurons of both vertebrates and invertebrates and seem to be related to the rhythmic activity of central neural networks. In this study, we analyzed the effect of antidromic discharges on the sensory activity of a leg proprioceptor in in vitro preparations of the crayfish CNS. Intracellular microelectrodes were used both to record the orthodromic spikes and to elicit antidromic spikes by injecting squares pulses of depolarizing current at various frequencies. Experiments were performed on the three types of identified sensory afferents (tonic, phasotonic, and phasic). The main results showed a reduction of the firing frequency of the orthodromic activity in 82% of the tested afferents. In tonic afferents, during their occurrences and according to their frequency, antidromic spikes or bursts reduced or suppressed the orthodromic activity. Following their terminations, they also induced a silent period and a gradual recovery of the orthodromic activity, both of which increased as the duration and the frequency of the antidromic bursts increased. In phasotonic and phasic afferents, antidromic bursts reduced or suppressed the phasic responses as their frequency and durations increased. In phasotonic afferents, if elicited prior to the movements, long-duration bursts with increasing frequency reduced more rapidly the tonic background activity than the phasic one whereas short-duration bursts at high frequency produced strong decreases of both. The effect of antidromic bursts accumulated when they are repetitively elicited. Antidromic bursts induced a much larger decrease of the sensory activity than adaptation alone. The occurrences of antidromic spikes or bursts may have a functional role

  11. Section AA Pre2004 Fire, Section AA 2009, Section AA, South ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Section A-A Pre-2004 Fire, Section A-A 2009, Section A-A, South Elevation - Boston & Maine Railroad, Berlin Branch Bridge #148.81, Formerly spanning Moose Brook at former Boston & Maine Railroad, Gorham, Coos County, NH

  12. Short-latency afferent inhibition in chronic spinal cord injury

    PubMed Central

    Bailey, Aaron Z.; Mi, Yiqun P.; Nelson, Aimee J.

    2015-01-01

    Background Short-latency afferent inhibition (SAI) results when somatosensory afferent input inhibits the corticospinal output from primary motor cortex (M1). The present study examined SAI in the flexor carpi radialis (FCR) muscle in individuals with spinal cord injury (SCI) and uninjured controls. Methods Short-latency afferent inhibition (SAI) was evoked by stimulating the median nerve at the elbow at intervals of 15, 20 and 25 ms in advance of a transcranial magnetic stimulation (TMS) pulse over M1. SAI was tested with the FCR at rest and also during ~20% of maximum voluntary contraction. Corticospinal output was assessed through measuring both motor thresholds and motor evoked potential (MEP) recruitment curves. The afferent volley was assessed via the N20–P25 amplitude of the somatosensory evoked potential (SEP) and the amplitude of sensory nerve action potentials (SNAP) recorded over the median nerve at the elbow. Results SAI is reduced in SCI in both the contracted and non-contracted FCR muscle. MEP recruitment curves and thresholds were decreased in SCI only in the active state and not the resting state. N20–P25 amplitude was similar between groups in both the resting and active states although SNAP was significantly reduced in SCI at rest. Conclusions We conclude that reduced SAI in SCI is likely attributed to neuroplasticity altering the intrinsic M1 circuitry mediating SAI and/or reduced afferent input traversing a direct thalamocortical route to M1. These data provide a new avenue of research aimed at identifying therapeutic approaches to alter SAI to improve upper limb function in individuals with SCI. PMID:28123808

  13. Neck muscle afferents influence oromotor and cardiorespiratory brainstem neural circuits.

    PubMed

    Edwards, I J; Lall, V K; Paton, J F; Yanagawa, Y; Szabo, G; Deuchars, S A; Deuchars, J

    2015-01-01

    Sensory information arising from the upper neck is important in the reflex control of posture and eye position. It has also been linked to the autonomic control of the cardiovascular and respiratory systems. Whiplash associated disorders (WAD) and cervical dystonia, which involve disturbance to the neck region, can often present with abnormalities to the oromotor, respiratory and cardiovascular systems. We investigated the potential neural pathways underlying such symptoms. Simulating neck afferent activity by electrical stimulation of the second cervical nerve in a working heart brainstem preparation (WHBP) altered the pattern of central respiratory drive and increased perfusion pressure. Tracing central targets of these sensory afferents revealed projections to the intermedius nucleus of the medulla (InM). These anterogradely labelled afferents co-localised with parvalbumin and vesicular glutamate transporter 1 indicating that they are proprioceptive. Anterograde tracing from the InM identified projections to brain regions involved in respiratory, cardiovascular, postural and oro-facial behaviours--the neighbouring hypoglossal nucleus, facial and motor trigeminal nuclei, parabrachial nuclei, rostral and caudal ventrolateral medulla and nucleus ambiguus. In brain slices, electrical stimulation of afferent fibre tracts lateral to the cuneate nucleus monosynaptically excited InM neurones. Direct stimulation of the InM in the WHBP mimicked the response of second cervical nerve stimulation. These results provide evidence of pathways linking upper cervical sensory afferents with CNS areas involved in autonomic and oromotor control, via the InM. Disruption of these neuronal pathways could, therefore, explain the dysphagic and cardiorespiratory abnormalities which may accompany cervical dystonia and WAD.

  14. Targeting vascular amyloid in arterioles of Alzheimer disease transgenic mice with amyloid β protein antibody-coated nanoparticles.

    PubMed

    Poduslo, Joseph F; Hultman, Kristi L; Curran, Geoffry L; Preboske, Gregory M; Chamberlain, Ryan; Marjańska, Małgorzata; Garwood, Michael; Jack, Clifford R; Wengenack, Thomas M

    2011-08-01

    The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that uses a monoclonal antibody against fibrillar human amyloid-β42 that is surface coated onto a functionalized phospholipid monolayer. We demonstrate that this conjugated nanoparticle binds to CVA deposits in arterioles of AD transgenic mice (Tg2576) after infusion into the external carotid artery using 3 different approaches. The first 2 approaches use a blood vessel enrichment of homogenized brain and a leptomeningeal vessel preparation from thin tangential brain slices from the surface of the cerebral cortex. Targeting of CVA by the antibody-coated nanoparticle was visualized using fluorescent lissamine rhodamine-labeled phospholipids in the nanoparticles, which were compared with fluorescent staining of the endothelial cells and amyloid deposits using confocal laser scanning microscopy. The third approach used high-field strength magnetic resonance imaging of antibody-coated iron oxide nanoparticles after infusion into the external carotid artery. Dark foci of contrast enhancement in cortical arterioles were observed in T2*-weighted images of ex vivo AD mouse brains that correlated histologically with CVA deposits. The targeting ability of these nanoparticles to CVA provides opportunities for the prevention and treatment of CAA.

  15. Targeting Vascular Amyloid in Arterioles of Alzheimer Disease Transgenic Mice with Amyloid Beta Protein Antibody-Coated Nanoparticles

    PubMed Central

    Poduslo, Joseph F.; Hultman, Kristi L.; Curran, Geoffry L.; Preboske, Gregory M.; Chamberlain, Ryan; Marjańska, Małgorzata; Garwood, Michael; Jack, Clifford R.; Wengenack, Thomas M.

    2015-01-01

    The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that utilizes a monoclonal antibody against fibrillar human amyloid-β42 that is surface-coated onto a functionalized phospholipid monolayer. We demonstrate that this conjugated nanoparticle binds to CVA deposits in arterioles of AD transgenic mice (Tg2576) following infusion into the external carotid artery using 3 different approaches. The first 2 approaches utilize a blood vessel enrichment of homogenized brain and a leptomeningeal vessel preparation from thin tangential brain slices from the surface of the cerebral cortex. Targeting of CVA by the antibody-coated nanoparticle was visualized using fluorescent lissamine rhodamine-labeled phospholipids in the nanoparticles, which were compared with fluorescent staining of the endothelial cells and amyloid deposits utilizing confocal laser scanning microscopy. The third approach utilized high field strength magnetic resonance imaging of antibody-coated iron oxide nanoparticles (MIONs) following infusion into the external carotid artery. Dark foci of contrast enhancement in cortical arterioles were observed in T2*-weighted images of ex vivo AD mouse brains that correlated histologically with CVA deposits. The targeting ability of these nanoparticles to CVA provides opportunities for the prevention and treatment of CAA. PMID:21760540

  16. Androgen Action via Testicular Arteriole Smooth Muscle Cells Is Important for Leydig Cell Function, Vasomotion and Testicular Fluid Dynamics

    PubMed Central

    Welsh, Michelle; Sharpe, Richard M.; Moffat, Lindsey; Atanassova, Nina; Saunders, Philippa T. K.; Kilter, Sigrid; Bergh, Anders; Smith, Lee B.

    2010-01-01

    Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis. PMID:21049031

  17. Senescence marker protein-30 (SMP30) deficiency impairs myocardium-induced dilation of coronary arterioles associated with reactive oxygen species.

    PubMed

    Mizukami, Hiroyuki; Saitoh, Shu-Ichi; Machii, Hirofumi; Yamada, Shinya; Hoshino, Yasuto; Misaka, Tomofumi; Ishigami, Akihito; Takeishi, Yasuchika

    2013-04-29

    Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30's effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT) mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria) decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium.

  18. Coronary Arterioles in Type 2 Diabetic (db/db) Mice Undergo a Distinct Pattern of Remodeling Associated with Decreased Vessel Stiffness

    PubMed Central

    Katz, Paige S.; Trask, Aaron J.; Souza-Smith, Flavia M.; Hutchinson, Kirk R.; Galantowicz, Maarten L.; Lord, Kevin C.; Stewart, James A.; Cismowski, Mary J.; Varner, Kurt J.; Lucchesi, Pamela A.

    2011-01-01

    Background Little is known about the impact of type 2 diabetes mellitus (DM) on coronary arteriole remodeling. The aim of this study was to determine the mechanisms that underlie coronary arteriole structural remodeling in type 2 diabetic (db/db) mice. Methods and Results Passive structural properties of septal coronary arterioles isolated from 12- and 16-wk-old diabetic db/db and control mice were assessed by pressure myography. Coronary arterioles from 12-wk-old db/db mice were structurally similar to age-matched controls. By 16-wks of age, coronary wall thickness was increased in db/db arterioles (p < 0.01), while luminal diameter was reduced (Control: 118±5μm; db/db: 102±4μm, p < 0.05), augmenting the wall-to-lumen ratio by 58% (Control: 5.9±0.6; db/db: 9.5±0.4, p < 0.001). Inward hypertrophic remodeling was accompanied by a 56% decrease in elastic modulus (p < 0.05, indicating decreased vessel coronary wall stiffness) and a ~30% reduction in coronary flow reserve in diabetic mice. Interestingly, aortic pulse wave velocity and femoral artery incremental modulus were increased (p < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular tissue analysis revealed increased elastin-to-collagen ratio in diabetic coronaries when compared to control and a decrease in the same ratio in the diabetic aortas. Conclusions These data show that coronary arterioles isolated from type 2 diabetic mice undergo inward hypertrophic remodeling associated with decreased stiffness and increased elastin-to-collagen ratio which results in a decreased coronary flow reserve. This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM. PMID:21744279

  19. Adaptation of coronary microvascular exchange in arterioles and venules to exercise training and a role for sex in determining permeability responses

    PubMed Central

    Huxley, Virginia H.; Wang, Jian Jie; Sarelius, Ingrid H.

    2007-01-01

    Studies of physical performance and energy metabolism during and following exercise have shown significant sex-specific musculoskeletal adaptations; less is known of vascular adaptations, particularly with respect to exchange capacity. In response to adenosine (ADO), a metabolite produced during exercise, permeability (Ps) of coronary arterioles from female pigs changed acutely; the magnitude and direction of the change (ΔPs) were determined by training status. In the present study Ps to albumin was assessed in arterioles (n = 138) and venules (n = 24) isolated from hearts of male (N = 27) and female (N = 59) pigs in the exercise training group (EX). We evaluated the hypothesis that coronary microvessel exchange adapts to endurance exercise training not by altering basal Ps, per se, but by elevating Ps on exposure to ADO. In contrast, training resulted in a reduction of basal Ps in all arterioles, and in venules from males, with no change in venules from EX females. Exposure to ADO resulted in the predicted increase in Ps except for venules from EX males where Ps was reduced. ΔPs responses of arterioles to mediators of adenylyl cyclase (isoproterenol)- and guanylyl cyclase (atrial natriuretic peptide)-signaling pathways were attenuated in EX pigs relative to pigs in the sedentary group. The adaptation of EX arterioles involves an upregulation of a nitric oxide-dependent pathway since nitric oxide synthase inhibition blocks ΔPs by ADO. Thus adaptation of microvascular exchange capacity to endurance exercise training not only occurs but also involves multiple mechanisms that differ in arterioles and venules with their relative contribution to net flux being a function of sex. PMID:17434979

  20. Function and expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles.

    PubMed

    Westcott, Erika B; Goodwin, Erica L; Segal, Steven S; Jackson, William F

    2012-04-15

    We tested the hypothesis that vasomotor control is differentially regulated between feed arteries and downstream arterioles from the cremaster muscle of C57BL/6 mice. In isolated pressurized arteries, confocal Ca(2+) imaging of smooth muscle cells (SMCs) revealed Ca(2+) sparks and Ca(2+) waves. Ryanodine receptor (RyR) antagonists (ryanodine and tetracaine) inhibited both sparks and waves but increased global Ca(2+) and myogenic tone. In arterioles, SMCs exhibited only Ca(2+) waves that were insensitive to ryanodine or tetracaine. Pharmacological interventions indicated that RyRs are functionally coupled to large-conductance, Ca(2+)-activated K(+) channels (BK(Ca)) in SMCs of arteries, whereas BK(Ca) appear functionally coupled to voltage-gated Ca2+ channels in SMCs of arterioles. Inositol 1,4,5-trisphosphate receptor (IP3R) antagonists (xestospongin D or 2-aminoethoxydiphenyl borate) or a phospholipase C inhibitor (U73122) attenuated Ca(2+) waves, global Ca(2+) and myogenic tone in arteries and arterioles but had no effect on arterial sparks. Real-time PCR of isolated SMCs revealed RyR2 as the most abundant isoform transcript; arteries expressed twice the RyR2 but only 65% the RyR3 of arterioles and neither vessel expressed RyR1. Immunofluorescent localisation of RyR protein indicated bright, clustered staining of arterial SMCs in contrast to diffuse staining in arteriolar SMCs. Expression of IP(3)R transcripts and protein immunofluorescence were similar in SMCs of both vessels with IP(3)R1>IP(3)R2>IP(3)R3. Despite similar expression of IP(3)Rs and dependence of Ca(2+) waves on IP(3)Rs, these data illustrate pronounced regional heterogeneity in function and expression of RyRs between SMCs of the same vascular resistance network. We conclude that vasomotor control is differentially regulated in feed arteries vs. downstream arterioles.

  1. Function and expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles

    PubMed Central

    Westcott, Erika B; Goodwin, Erica L; Segal, Steven S; Jackson, William F

    2012-01-01

    We tested the hypothesis that vasomotor control is differentially regulated between feed arteries and downstream arterioles from the cremaster muscle of C57BL/6 mice. In isolated pressurized arteries, confocal Ca2+ imaging of smooth muscle cells (SMCs) revealed Ca2+ sparks and Ca2+ waves. Ryanodine receptor (RyR) antagonists (ryanodine and tetracaine) inhibited both sparks and waves but increased global Ca2+ and myogenic tone. In arterioles, SMCs exhibited only Ca2+ waves that were insensitive to ryanodine or tetracaine. Pharmacological interventions indicated that RyRs are functionally coupled to large-conductance, Ca2+-activated K+ channels (BKCa) in SMCs of arteries, whereas BKCa appear functionally coupled to voltage-gated Ca2+ channels in SMCs of arterioles. Inositol 1,4,5-trisphosphate receptor (IP3R) antagonists (xestospongin D or 2-aminoethoxydiphenyl borate) or a phospholipase C inhibitor (U73122) attenuated Ca2+ waves, global Ca2+ and myogenic tone in arteries and arterioles but had no effect on arterial sparks. Real-time PCR of isolated SMCs revealed RyR2 as the most abundant isoform transcript; arteries expressed twice the RyR2 but only 65% the RyR3 of arterioles and neither vessel expressed RyR1. Immunofluorescent localisation of RyR protein indicated bright, clustered staining of arterial SMCs in contrast to diffuse staining in arteriolar SMCs. Expression of IP3R transcripts and protein immunofluorescence were similar in SMCs of both vessels with IP3R1>>IP3R2>IP3R3. Despite similar expression of IP3Rs and dependence of Ca2+ waves on IP3Rs, these data illustrate pronounced regional heterogeneity in function and expression of RyRs between SMCs of the same vascular resistance network. We conclude that vasomotor control is differentially regulated in feed arteries vs. downstream arterioles. PMID:22331418

  2. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    PubMed

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned

  3. The AAS Workforce Survey

    NASA Astrophysics Data System (ADS)

    Postman, Marc; Norman, D. J.; Evans, N. R.; Ivie, R.

    2014-01-01

    The AAS Demographics Committee, on behalf of the AAS, was tasked with initiating a biennial survey to improve the Society's ability to serve its members and to inform the community about changes in the community's demographics. A survey, based in part on similar surveys for other scientific societies, was developed in the summer of 2012 and was publicly launched in January 2013. The survey randomly targeted 2500 astronomers who are members of the AAS. The survey was closed 4 months later (April 2013). The response rate was excellent - 63% (1583 people) completed the survey. I will summarize the results from this survey, highlighting key results and plans for their broad dissemination.

  4. Mechanical activation of angiotensin II type 1 receptors causes actin remodelling and myogenic responsiveness in skeletal muscle arterioles.

    PubMed

    Hong, Kwangseok; Zhao, Guiling; Hong, Zhongkui; Sun, Zhe; Yang, Yan; Clifford, Philip S; Davis, Michael J; Meininger, Gerald A; Hill, Michael A

    2016-12-01

    Candesartan, an inverse agonist of the type 1 angiotensin II receptor (AT1 R), causes a concentration-dependent inhibition of pressure-dependent myogenic tone consistent with previous reports of mechanosensitivity of this G protein-coupled receptor. Mechanoactivation of the AT1 R occurs independently of local angiotensin II production and the type 2 angiotensin receptor. Mechanoactivation of the AT1 R stimulates actin polymerization by a protein kinase C-dependent mechanism, but independently of a change in intracellular Ca(2+) . Using atomic force microscopy, changes in single vascular smooth muscle cell cortical actin are observed to remodel following mechanoactivation of the AT1 R. The Gq/11 protein-coupled angiotensin II type 1 receptor (AT1 R) has been shown to be activated by mechanical stimuli. In the vascular system, evidence supports the AT1 R being a mechanosensor that contributes to arteriolar myogenic constriction. The aim of this study was to determine if AT1 R mechanoactivation affects myogenic constriction in skeletal muscle arterioles and to determine underlying cellular mechanisms. Using pressure myography to study rat isolated first-order cremaster muscle arterioles the AT1 R inhibitor candesartan (10(-7) -10(-5)  m) showed partial but concentration-dependent inhibition of myogenic reactivity. Inhibition was demonstrated by a rightward shift in the pressure-diameter relationship over the intraluminal pressure range, 30-110 mmHg. Pressure-induced changes in global vascular smooth muscle intracellular Ca(2+) (using Fura-2) were similar in the absence or presence of candesartan, indicating that AT1 R-mediated myogenic constriction relies on Ca(2+) -independent downstream signalling. The diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) reversed the inhibitory effect of candesartan, while this rescue effect was prevented by the protein kinase C (PKC) inhibitor GF 109203X. Both candesartan and PKC inhibition caused increased G-actin levels

  5. Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

    NASA Technical Reports Server (NTRS)

    Schrage, William G.; Woodman, Christopher R.; Laughlin, M. Harold

    2002-01-01

    The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (approximately 300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of L-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

  6. Afferent projections to the deep mesencephalic nucleus in the rat

    SciTech Connect

    Veazey, R.B.; Severin, C.M.

    1982-01-10

    Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medial and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist.

  7. Influences of neck afferents on sympathetic and respiratory nerve activity.

    PubMed

    Bolton, P S; Kerman, I A; Woodring, S F; Yates, B J

    1998-11-15

    It is well established that the vestibular system influences the sympathetic nervous system and the respiratory system; presumably, vestibulosympathetic and vestibulorespiratory responses participate in maintaining stable blood pressure and blood oxygenation during movement and changes in posture. Many brainstem neurons that generate vestibulospinal reflexes integrate signals from the labyrinth and neck muscles to distinguish between head movements on a stable body and whole body movements. In the present study, responses were recorded from the splanchnic (sympathetic), hypoglossal (inspiratory) and abdominal (expiratory) nerves during stimulation of the C2 dorsal root ganglion or C2 or C3 nerve branches innervating dorsal neck muscles. Stimulation of neck afferents using low current intensities, in many cases less than twice the threshold for producing an afferent volley recordable from the cord dorsum, elicited changes in sympathetic and respiratory nerve activity. These data suggest that head rotation on a stable body would elicit both cervical and vestibular inputs to respiratory motoneurons and sympathetic preganglionic neurons. The effects of cervical afferent stimulation on abdominal, splanchnic and hypoglossal nerve activity were not abolished by transection of the brainstem caudal to the vestibular nuclei; thus, pathways in addition to those involving the vestibular nuclei are involved in relaying cervical inputs to sympathetic preganglionic neurons and respiratory motoneurons. Transection of the C1-3 dorsal roots enhanced responses of the splanchnic and abdominal nerves to pitch head rotations on a fixed body but diminished responses of the hypoglossal nerve. Thus, neck and vestibular afferent influences on activity of respiratory pump muscles and sympathetic outflow appear to be antagonistic, so that responses will occur during whole body movements but not head movements on a stationary trunk. In contrast, neck and vestibular influences on tongue

  8. Tonic Investigation Concept of Cervico-vestibular Muscle Afferents

    PubMed Central

    Dorn, Linda Josephine; Lappat, Annabelle; Neuhuber, Winfried; Scherer, Hans; Olze, Heidi; Hölzl, Matthias

    2016-01-01

    Introduction Interdisciplinary research has contributed greatly to an improved understanding of the vestibular system. To date, however, very little research has focused on the vestibular system's somatosensory afferents. To ensure the diagnostic quality of vestibular somatosensory afferent data, especially the extra cranial afferents, stimulation of the vestibular balance system has to be precluded. Objective Sophisticated movements require intra- and extra cranial vestibular receptors. The study's objective is to evaluate an investigation concept for cervico-vestibular afferents with respect to clinical feasibility. Methods A dedicated chair was constructed, permitting three-dimensional trunk excursions, during which the volunteer's head remains fixed. Whether or not a cervicotonic provocation nystagmus (c-PN) can be induced with static trunk excursion is to be evaluated and if this can be influenced by cervical monophasic transcutaneous electrical nerve stimulation (c-TENS) with a randomized test group. 3D-video-oculography (VOG) was used to record any change in cervico-ocular examination parameters. The occurring nystagmuses were evaluated visually due to the small caliber of nystagmus amplitudes in healthy volunteers. Results The results demonstrate: no influence of placebo-controlled c-TENS on the spontaneous nystagmus; a significant increase of the vertical nystagmus on the 3D-trunk-excursion chair in static trunk flexion with cervical provocation in all young healthy volunteers (n = 49); and a significant difference between vertical and horizontal nystagmuses during static trunk excursion after placebo-controlled c-TENS, except for the horizontal nystagmus during trunk torsion. Conclusion We hope this cervicotonic investigation concept on the 3D trunk-excursion chair will contribute to new diagnostic and therapeutic perspectives on cervical pathologies in vestibular head-to-trunk alignment. PMID:28050208

  9. Mechanically insensitive afferents (MIAs) in cutaneous nerves of monkey.

    PubMed

    Meyer, R A; Davis, K D; Cohen, R H; Treede, R D; Campbell, J N

    1991-10-11

    A problem in the study of nociceptors is that intense stimuli are used to locate the receptive field (RF), and thus the receptor may be damaged before the first responses are recorded. In addition, some nociceptors do not respond to the mechanical stimuli often used to search for the RF. To overcome these problems, an electrical search technique was developed to locate the RF of cutaneous nociceptors. In the hairy skin of anesthetized monkey, we used this technique to locate the RF of 63 A delta-fibers and 22 C-fibers that had extremely high thresholds or were unresponsive to mechanical stimuli. We refer to these afferents as mechanically insensitive afferents (MIAs). Ten A delta-fiber MIAs had a short latency response to stepped heat stimuli and could be responsible for first pain sensation. Five A delta-fiber MIAs and one C-fiber MIA did not respond to mechanical or heat stimuli but did respond to injection into the electrical RF of an artificial inflammatory soup containing histamine, bradykinin, prostaglandin E1, and serotonin. These chemoreceptors might be responsible for the pain and itch sensations that result from chemical stimuli. Some MIAs became more responsive to mechanical stimuli after injection into the RF of the inflammatory soup and, thus, may contribute to the hyperalgesia to mechanical stimuli associated with cutaneous injury. A large proportion of the A delta-fiber (48%) and C-fiber (30%) afferents in this study were insensitive to mechanical stimuli. The role of these MIAs in sensation needs to be studied further. The electrical search technique enables a systematic study of these afferents to be performed. This technique may also be of use to identify and characterize dorsal horn neurons that have inputs from MIAs.

  10. Afferent connections of the cerebellum in various types of reptiles.

    PubMed

    Bangma, G C; ten Donkelaar, H

    1982-05-20

    The origin of cerebellar afferents was studied in various types of reptiles, viz., the turtles Pseudemys scripta elegans and Testudo hermanni, the lizard Varanus exanthematicus, and the snake Python regius, with retrograde tracers (the enzyme horseradish peroxidase and the fluorescent tracer "Fast Blue"). Projections to the cerebellum were demonstrated from the nucleus of the basal optic root, the interstitial nucleus of the fasciculus longitudinalis medialis, the vestibular ganglion, and the vestibular nuclear complex, two somatosensory nuclei, viz., the descending nucleus of the trigeminal nerve and the nucleus of the dorsal funiculus, the nucleus of the solitary tract, the reticular formation, and throughout the spinal cord. A distinct bilateral projection to the cerebellum was found to arise in a nucleus previously called nucleus parvocellularis medialis (Ebbesson, '67). In the present study this cell mass is termed the perihypoglossal nuclear complex, considering its comparable position and fiber connections to the perihypoglossal nuclei in mammals. In all reptilian species studied a contralateral cerebellar projection of a cell mass located in the caudal brainstem adjacent to the nucleus raphes inferior was observed. It seems likely that this cell mass represents the reptilian homologue of the mammalian inferior olive. Most of the spinocerebellar fibers appeared to arise in neurons located in area VII-VIII of the gray matter. In this respect the origin of the spinocerebellar projection in reptiles resembles the origin of the rostral and ventral spinocerebellar tracts in mammals. No indications for the existence of a column of Clarke or a central cervical nucleus in the reptilian spinal cord were obtained. On comparison of the cerebellum afferents in reptiles with the known connections of the cerebellum in amphibians, birds, and mammals, a basic pattern of cerebellar afferent projections appears to exist in these vertebrate classes, including retinal

  11. AAS 227: Welcome!

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Greetings from the 227th American Astronomical Society meeting in Kissimmee, Florida! This week, along with several fellow authors from astrobites, Iwill bewritingupdates on selectedevents at themeeting and posting at the end of each day. You can follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.If youre an author or referee (or plan to be!) and youre here at the meeting, consider joining us at our Author and Referee Workshop on Wednesday in the Tallahassee room, where well be sharingsome of the exciting new features of the AAS journals. You can drop intoeither of the two-hour sessions(10 AM 12 PM or 1 PM 3 PM), and there will be afree buffet lunch at noon.Heres the agenda:Morning SessionTopic Speaker10:00 am 10:05 amIntroductionsJulie Steffen10:05 am 10:35 amChanges at AAS Journals; How to Be a Successful AAS AuthorEthan Vishniac10:35 am 11:00 amThe Peer Review ProcessButler Burton11:00 am 11:15 amAAS Nova: Sharing AAS Authors Research with the Broader CommunitySusanna Kohler11:15 am 11:30 amFixing Software and Instrumentation Publishing: New Paper Styles in AAS JournalsChris Lintott11:30 am 11:45 amMaking Article Writing Easier with the New AASTeX v6.0Greg Schwarz11:45 am 12:00 pmBringing JavaScript and Interactivity to Your AAS Journal FiguresGus MuenchLunch SessionTopic Speaker12:00 pm 12:15 pmUnified Astronomy ThesaurusKatie Frey12:15 pm 12:30 pmAAS/ADS ORCID Integration ToolAlberto Accomazzi12:30 pm 12:45 pmWorldWide Telescope and Video AbstractsJosh Peek12:45 pm 01:00 pmArizona Astronomical Data Hub (AADH)Bryan HeidornAfternoon SessionTopic Speaker01:00 pm 01:05 pmIntroductionsJulie Steffen01:05 pm 01:35 pmChanges at AAS Journals; How to Be a Successful AAS AuthorEthan Vishniac01:35 pm 02:00 pmThe Peer Review ProcessButler Burton02:00 pm 02:15 pmAAS Nova: Sharing AAS Authors Research with the Broader CommunitySusanna Kohler02:15 pm 02:30 pm

  12. AAS 228: Welcome!

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Greetings from the 228th American Astronomical Society meeting in San Diego, California! This week, along with a team of fellow authorsfrom astrobites, Iwill bewritingupdates on selectedevents at themeeting and posting twiceeach day. You can follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.If youre at the meeting, come stop by the AAS booth (Booth #211-213) to learn about the newly-announced partnership between AAS and astrobites and pick up some swag.And dont forget to visit the IOP booth in the Exhibit Hall (Booth #223) to learn more about the new corridors for AAS Journals and to pick up a badge pin to representyour corridor!

  13. The efferent and afferent connections of the supplementary motor area.

    PubMed

    Jürgens, U

    1984-05-21

    The efferent and afferent connections of the supplementary motor area (SMA) were studied in 6 squirrel monkeys using [3H]leucine and horseradish peroxidase, respectively. Efferent projections, common to all leucine-injected animals, were found to the cortical areas 9,8,44,4,2,5,7,24 and 23. Subcortically , efferents were found to the putamen, caudate nucleus, claustrum, the thalamic nuclei reticularis, ventrialis anterior, ventralis lateralis, medialis dorsalis, centralis lateralis, paracentralis , centrum medianum, parafascicularis, centralis superior lateralis, centralis inferior and lateralis posterior, the subthalamic nucleus, field H of Forel, nuel . ruber, reticular formation of midbrain, pons and medulla, the pontine gray and nucl . reticularis tegmenti pontis. Afferent connections exist with the cortical areas 9,8,6,44,4,1,2,5,7, 24 and 23, insula, fronto-parietal operculum and superior temporal sulcus. Subcortical afferent connections exist with the claustrum, nucleus of the diagonal band, nucl . basalis Meynert, basolateral amygdaloid nucleus, the thalamic nuclei ventralis anterior, ventralis lateralis, medialis dorsalis, centralis lateralis, paracentralis , centrum medianum, centralis superior lateralis, centralis inferior, lateralis posterior and pulvinaris , the posterior hypothalamus, ventral tegmental area, nucl . ruber pars parvicellularis , reticular formation of midbrain and pons, locus coeruleus and nucl . centralis superior Bechterew. The projections are discussed with respect to the possible role SMA plays in the voluntary initiation of motor actions.

  14. Transfer characteristics of the hair cell's afferent synapse

    NASA Astrophysics Data System (ADS)

    Keen, Erica C.; Hudspeth, A. J.

    2006-04-01

    The sense of hearing depends on fast, finely graded neurotransmission at the ribbon synapses connecting hair cells to afferent nerve fibers. The processing that occurs at this first chemical synapse in the auditory pathway determines the quality and extent of the information conveyed to the central nervous system. Knowledge of the synapse's input-output function is therefore essential for understanding how auditory stimuli are encoded. To investigate the transfer function at the hair cell's synapse, we developed a preparation of the bullfrog's amphibian papilla. In the portion of this receptor organ representing stimuli of 400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one to three hair cells. By performing simultaneous voltage-clamp recordings from presynaptic hair cells and postsynaptic afferent fibers, we established that the rate of evoked vesicle release, as determined from the average postsynaptic current, depends linearly on the amplitude of the presynaptic Ca2+ current. This result implies that, for receptor potentials in the physiological range, the hair cell's synapse transmits information with high fidelity. auditory system | exocytosis | glutamate | ribbon synapse | synaptic vesicle

  15. Subcortical afferent connections of the amygdala in the monkey

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1980-01-01

    The cells of origin of the afferent connections of the amygdala in the rhesus and squirrel monkeys are determined according to the retrograde axonal transport of the enzyme horseradish peroxidase injected into various quadrants of the amygdala. Analysis of the distribution of enzyme-labeled cells reveals afferent amygdalar connections with the ipsilateral halves of the midline nucleus paraventricularis thalami and both the parvo- and magnocellular parts of the nucleus subparafascicularis in the dorsal thalamus, all the subdivisions of the midline nucleus centralis complex, the nucleus reuniens ventralis and the nucleus interventralis. The largest populations of enzyme-labeled cells in the hypothalamus are found to lie in the middle and posterior parts of the ipsilateral, lateral hypothalamus and the ventromedial hypothalamic nucleus, with scattered cells in the supramammillary and dorsomedial nuclei and the posterior hypothalamic area, Tsai's ventral tegmental area, the rostral and caudal subdivisions of the nucleus linearis in the midbrain and the dorsal raphe nucleus. The most conspicuous subdiencephalic source of amygdalar afferent connections is observed to be the pars lateralis of the nucleus parabrachialis in the dorsolateral pontine tegmentum, with a few labeled cells differentiated from pigmented cells in the locus coeruleus.

  16. The visceromotor and somatic afferent nerves of the penis.

    PubMed

    Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

    2015-05-01

    Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

  17. Vagal Afferent Innervation of the Lower Esophageal Sphincter

    PubMed Central

    Powley, Terry L.; Baronowsky, Elizabeth A.; Gilbert, Jared M.; Hudson, Cherie N.; Martin, Felecia N.; Mason, Jacqueline K.; McAdams, Jennifer L.; Phillips, Robert J.

    2013-01-01

    To supply a fuller morphological characterization of the vagal afferents innervating the lower esophageal sphincter (LES), specifically to label vagal terminals in the tissues forming the LES in the gastroesophageal junction, the present experiment employed injections of dextran biotin into the nodose ganglia of rats. Four types of vagal afferents innervated the LES. Clasp and sling muscle fibers were directly and prominently innervated by intramuscular arrays (IMAs). Individual IMA terminals subtended about 16° of arc of the esophageal circumference, and, collectively, the terminal fields were distributed within the muscle ring to establish a 360° annulus of mechanoreceptors in the sphincter wall. 3D morphometry of the terminals established that, compared to sling muscle IMAs, clasp muscle IMAs had more extensive arbors and larger receptive fields. In addition, at the cardia, local myenteric ganglia between smooth muscle sheets and striated muscle bundles were innervated by intraganglionic laminar endings (IGLEs), in a pattern similar to the innervation of the myenteric plexus throughout the stomach and esophagus. Finally, as previously described, the principle bundle of sling muscle fibers that links LES sphincter tissue to the antropyloric region of the lesser curvature was innervated by exceptionally long IMAs as well as by unique web ending specializations at the distal attachment of the bundle. Overall, the specialized varieties of densely distributed vagal afferents innervating the LES underscore the conclusion that these sensory projections are critically involved in generating LES reflexes and may be promising targets for managing esophageal dysfunctions. PMID:23583280

  18. Neck afferent involvement in cardiovascular control during movement

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Ray, C. A.

    2000-01-01

    It is well established that labyrinth and neck afferent information contributes to the regulation of somatomotor function during movement and changes in posture. There is also convincing evidence that the vestibular system participates in the modulation of sympathetic outflow and cardiovascular function during changes in posture, presumably to prevent orthostatic hypotension. However, the labyrinth organs do not provide any signals concerning body movements with respect to the head. In contrast, the neck receptors, particularly muscle spindles, are well located and suited to provide information about changes in body position with respect to the head and vestibular signals. Studies in the cat suggest that neck afferent information may modulate the vestibulosympathetic reflex responses to head-neck movements. There is some evidence in the cat to suggest involvement of low threshold mechanoreceptors. However, human studies do not indicate that low threshold mechanoreceptors in the neck modulate cardiovascular responses. The human studies are consistent with the studies in the cat in that they demonstrate the importance of otolith activation in mediating cardiovascular and sympathetic responses to changes in posture. This paper briefly reviews the current experimental evidence concerning the involvement of neck afferent information in the modulation of cardiovascular control during movement and changes in posture.

  19. Subcortical afferent connections of the amygdala in the monkey

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1980-01-01

    The cells of origin of the afferent connections of the amygdala in the rhesus and squirrel monkeys are determined according to the retrograde axonal transport of the enzyme horseradish peroxidase injected into various quadrants of the amygdala. Analysis of the distribution of enzyme-labeled cells reveals afferent amygdalar connections with the ipsilateral halves of the midline nucleus paraventricularis thalami and both the parvo- and magnocellular parts of the nucleus subparafascicularis in the dorsal thalamus, all the subdivisions of the midline nucleus centralis complex, the nucleus reuniens ventralis and the nucleus interventralis. The largest populations of enzyme-labeled cells in the hypothalamus are found to lie in the middle and posterior parts of the ipsilateral, lateral hypothalamus and the ventromedial hypothalamic nucleus, with scattered cells in the supramammillary and dorsomedial nuclei and the posterior hypothalamic area, Tsai's ventral tegmental area, the rostral and caudal subdivisions of the nucleus linearis in the midbrain and the dorsal raphe nucleus. The most conspicuous subdiencephalic source of amygdalar afferent connections is observed to be the pars lateralis of the nucleus parabrachialis in the dorsolateral pontine tegmentum, with a few labeled cells differentiated from pigmented cells in the locus coeruleus.

  20. Neck afferent involvement in cardiovascular control during movement

    NASA Technical Reports Server (NTRS)

    Bolton, P. S.; Ray, C. A.

    2000-01-01

    It is well established that labyrinth and neck afferent information contributes to the regulation of somatomotor function during movement and changes in posture. There is also convincing evidence that the vestibular system participates in the modulation of sympathetic outflow and cardiovascular function during changes in posture, presumably to prevent orthostatic hypotension. However, the labyrinth organs do not provide any signals concerning body movements with respect to the head. In contrast, the neck receptors, particularly muscle spindles, are well located and suited to provide information about changes in body position with respect to the head and vestibular signals. Studies in the cat suggest that neck afferent information may modulate the vestibulosympathetic reflex responses to head-neck movements. There is some evidence in the cat to suggest involvement of low threshold mechanoreceptors. However, human studies do not indicate that low threshold mechanoreceptors in the neck modulate cardiovascular responses. The human studies are consistent with the studies in the cat in that they demonstrate the importance of otolith activation in mediating cardiovascular and sympathetic responses to changes in posture. This paper briefly reviews the current experimental evidence concerning the involvement of neck afferent information in the modulation of cardiovascular control during movement and changes in posture.

  1. Receptive field properties of human periodontal afferents responding to loading of premolar and molar teeth.

    PubMed

    Johnsen, Skjalg E; Trulsson, Mats

    2003-03-01

    Impulses in 45 single mechanoreceptive afferents were recorded from the human inferior alveolar nerve with permucosally inserted tungsten microelectrodes. All afferents responded to mechanical stimulation of one or more premolar or molar teeth and most likely innervated their periodontal ligaments. For each afferent, isolated "ramp-and-hold" shaped force profiles of similar magnitudes (252 +/- 24 mN; mean +/- SD) were applied to the lower first premolar, the second premolar, and the first molar on the recording side. The tooth loads were applied in six directions: lingual, facial, mesial, and distal in the horizontal plane and up and down in the vertical direction of the tooth. The afferents response during the static phase of the stimulus was analyzed. All afferents were slowly adapting, discharging continuously in response to static forces in at least one stimulation direction. Twenty-nine afferents (64%) were spontaneously active, exhibiting an ongoing discharge in the absence of external stimulation. Stimulation of a single tooth was found to excite each afferent most strongly. The most sensitive tooth (MST) was the first premolar for 23, the second premolar for 13, and the first molar for 9 afferents. About half of the afferent population also responded to loading of one or two more teeth. The response profiles of these afferents indicated that the multiple-teeth receptive fields were due to mechanical coupling between the teeth rather than branching of single afferents to innervate several teeth. The afferent responses to loading the mesial and distal halves of the first molars were very similar. Thus both intensive and directional aspects of the afferent response when loading one side of the tooth was preserved to a great extent when loading the other side. When loading the MST, the afferents typically showed excitatory responses in two to four of the six stimulation directions, i.e., the afferents were broadly tuned to direction of tooth loading. In the

  2. Fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal.

    PubMed

    Rosenblum, William I

    2008-10-01

    Cerebral hemorrhage in hypertensive patients is still an important source of morbidity and death. Understanding its underlying pathological basis is essential for the development of fact-based attempts to prevent the hemorrhage. Fibrinoid necrosis and miliary aneurysms are associated with and are the probable underlying causative lesions. Unfortunately much misunderstanding and confusion surrounds understanding of both lesions. This review clarifies several points. These include the following: the nature of fibrinoid necrosis and the susceptibility of small brain arteries and arterioles to this lesion even in the so-called benign hypertension; the relationship of fibrinoid necrosis to lipohyalinosis and the reasons for preferring the term fibrinoid; the existence of miliary aneurysms; the distinction between these aneurysms and pseudo-aneurysms or fibrin globes; the importance of, and basis for, recognizing healed miliary aneurysms; the relationship of fibrinoid necrosis to these aneurysms.

  3. Vestibular afferent responses to linear accelerations in the alert squirrel monkey

    NASA Technical Reports Server (NTRS)

    Somps, Christopher J.; Schor, Robert H.; Tomko, David L.

    1994-01-01

    The spontaneous activity of 40 otolith afferents and 44 canal afferents was recorded in 4 alert, intact squirrel monkeys. Polarization vectors and response properties of otolith afferents were determined during static re-orientations relative to gravity and during Earth-horizontal, sinusoidal, linear oscillations. Canal afferents were tested for sensitivity to linear accelerations. For regular otolith afferents, a significant correlation between upright discharge rate and sensitivity to dynamic acceleration in the horizontal plane was observed. This correlation was not present in irregular units. The sensitivity of otolith afferents to both static tilts and dynamic linear acceleration was much greater in irregularly discharging units than in regularly discharging units. The spontaneous activity and static and dynamic response properties of regularly discharging otolith afferents were similar to those reported in barbiturate-anesthetized squirrel monkeys. Irregular afferents also had similar dynamic response properties when compared to anesthetized monkeys. However, this sample of irregular afferents in alert animals had higher resting discharge rates and greater sensitivity to static tilts. The majority of otolith polarization vectors were oriented near the horizontal in the plane of the utricular maculae; however, directions of maximum sensitivity were different during dynamic and static testing. Canal afferents were not sensitive to static tilts or linear oscillations of the head.

  4. Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for ‘collateral failure' and infarct expansion after ischemic stroke

    PubMed Central

    Beard, Daniel J; McLeod, Damian D; Logan, Caitlin L; Murtha, Lucy A; Imtiaz, Mohammad S; van Helden, Dirk F; Spratt, Neil J

    2015-01-01

    Recent human imaging studies indicate that reduced blood flow through pial collateral vessels (‘collateral failure') is associated with late infarct expansion despite stable arterial occlusion. The cause for ‘collateral failure' is unknown. We recently showed that intracranial pressure (ICP) rises dramatically but transiently 24 hours after even minor experimental stroke. We hypothesized that ICP elevation would reduce collateral blood flow. First, we investigated the regulation of flow through collateral vessels and the penetrating arterioles arising from them during stroke reperfusion. Wistar rats were subjected to intraluminal middle cerebral artery (MCA) occlusion (MCAo). Individual pial collateral and associated penetrating arteriole blood flow was quantified using fluorescent microspheres. Baseline bidirectional flow changed to MCA-directed flow and increased by >450% immediately after MCAo. Collateral diameter changed minimally. Second, we determined the effect of ICP elevation on collateral and watershed penetrating arteriole flow. Intracranial pressure was artificially raised in stepwise increments during MCAo. The ICP increase was strongly correlated with collateral and penetrating arteriole flow reductions. Changes in collateral flow post-stroke appear to be primarily driven by the pressure drop across the collateral vessel, not vessel diameter. The ICP elevation reduces cerebral perfusion pressure and collateral flow, and is the possible explanation for ‘collateral failure' in stroke-in-progression. PMID:25669909

  5. Effect of hypergravity on the development of vestibulocerebellar afferent fibers

    NASA Astrophysics Data System (ADS)

    Bruce, L. L.

    Gravity is a critical factor in the normal development of the vestibular system, as prolonged prenatal exposures to either micro- or hypergravity will alter the pattern of projections from specific vestibular organs to specific targets in the vestibular nuclei. This study addresses the effect of gravity on the development of vestibulocerebellar projections. In adult rats the semicircular canal afferents project mainly to the cerebellar nodulus whereas the otolith maculae project mainly to the ventral uvula of the cerebellum. To determine if the distribution pattern of these afferents is altered by exposures to altered gravity, 10 pregnant rats were exposed to hypergravity (1.5g) from embryonic day 12 (before vestibular ganglion neurons contact vestibular nuclei) to embryonic day 21 (near the time when the vestibular system becomes functional). Controls were exposed to Earth's gravity but otherwise received the same treatment. At the end of the exposure the embryos were deeply anesthetized and fixed by transcardiac perfusion with 4% paraformaldehyde in 0.1 M phosphate buffer (pH7.4). Filter strips coated with DiI and PTIR were implanted into the saccule (gravistatic vestibular receptor) or into the posterior vertical canal (angular acceleration receptor), and allowed to diffuse for 2 weeks at 37°C. Then the brains were dissected and sectioned for fluorescent confocal imaging. Examination of the control cerebella revealed that the canal and otolith afferents have reached the nodulus and uvula, and axons extend into the internal granular, Purkinje, and molecular layers. Projections from the saccule and posterior vertical canal were partially segregated into their respective domains, the uvula and nodulus. In contrast, in hypergravity-exposed rat fetuses the saccule and posterior vertical canal projections were poorly segregated, and both organs contributed labeled fibers to all layers of the nodulus and uvula. This contrasts with the increased afferent segregation

  6. Low-threshold mechanoreceptive afferents in the human lingual nerve.

    PubMed

    Trulsson, M; Essick, G K

    1997-02-01

    Intrafascicular multiunit activity and impulses in single mechanoreceptive afferents were recorded from the human lingual nerve with permucosally inserted tungsten microelectrodes. Nylon filaments and blunt glass probes were used for mechanical stimulation of the mucosa of the dorsal surface of the tongue. The innervation territories of nine nerve fascicles were mapped during multiunit recordings. All fascicle fields included the tip of the tongue, suggesting a particularly high innervation density for this area. Thirty-three single mechanoreceptive afferents were isolated and studied. Of these afferents, 22 were characterized by very small mucosal receptive fields (range: 1-19.6 mm2; geometric mean: 2.4 mm2) and responded to extremely low mechanical forces (force threshold range: 0.03-2 mN; geometric mean: 0.15 mN). As such, it was concluded that these "superficial" units terminated near the surface of the tongue. The remaining 11 units responded to probing of large areas of the tongue (> 200 mm2) and exhibited high force thresholds (> or = 4 mN). It was concluded that these "deep" units terminated in the muscle mass of the tongue. Fourteen of the superficial units were classified as rapidly adapting and resembled the fast-adapting type I afferents described for the glabrous skin of the human hand. The rapidly adapting units responded both during the application and removal of, but not during maintenance of, the mechanical stimuli on the receptive field. Two types of slowly adapting responses were observed. One type (characteristic of only 2 units) was characterized by a pronounced sensitivity to force change during the application and removal of the mechanical stimuli and an irregular static discharge during maintenance of the stimulus on the receptive field. In contrast, the other six units exhibited a weak sensitivity to force change, a highly regular static discharge, and spontaneous activity. As such, these two types of slowly adapting units resembled the

  7. Afferent fibers supplying the uterus in the rat.

    PubMed

    Berkley, K J; Robbins, A; Sato, Y

    1988-01-01

    1. In the present three-part study electrophysiological techniques were used to characterize responses of afferent fibers in the rat hypogastric nerve to mechanical or chemical stimulation of the uterus, and anatomical techniques were used to identify the spinal segments through which uterine afferent fibers enter the spinal cord. 2. In an in vivo barbiturate-anesthetized preparation, hypogastric afferent fibers responded in a time-locked manner to mechanical stimulation confined to restricted regions of the uterus and adjacent ligament. Receptive fields were most often located on the uterine body, particularly over the cervix. The few located on the uterine horn were usually near regions irritated during preparative surgery. Effective mechanical stimuli (pressure, stretching, squeezing, probing, rarely contractions) were typically greater than 5 g and simultaneously accompanied by transient ischemia around the probe or contracted area. Distension, unless extreme, was not an effective stimulus. Retrospective analysis of the data indicated that fibers may be more sensitive to uterine stimulation when rats are in vaginal estrus/proestrus than in diestrus/metestrus. 3. In an in vitro preparation, hypogastric afferent fibers responded in a dose-dependent fashion to injections into the uterine artery of the algesic chemicals bradykinin, 5-hydroxytryptamine, and KCl. They also responded to high doses of CO2 (in saline) and NaCN, but rarely to lower doses. Nearly all fibers responded to more than one chemical with response characteristics unique to each chemical (e.g., latency, duration, peak rate). 4. Injections of horseradish peroxidase into the uterine body and small portions of the adjacent horns in rats in vaginal estrus consistently labeled a small number of cells in the L1-S1 dorsal root ganglia, with peaks at L2 and L6. Virtually no cells were labeled in rats whose estrous cycle had been disrupted (by inadvertently keeping them in constant light conditions for

  8. Human intersegmental reflexes from intercostal afferents to scalene muscles.

    PubMed

    McBain, Rachel A; Taylor, Janet L; Gorman, Robert B; Gandevia, Simon C; Butler, Jane E

    2016-10-01

    What is the central question of this study? The aim was to determine whether specific reflex connections operate between intercostal afferents and the scalene muscles in humans, and whether these connections operate after a clinically complete cervical spinal cord injury. What is the main finding and its importance? This is the first description of a short-latency inhibitory reflex connection between intercostal afferents from intercostal spaces to the scalene muscles in able-bodied participants. We suggest that this reflex is mediated by large-diameter afferents. This intercostal-to-scalene inhibitory reflex is absent after cervical spinal cord injury and may provide a way to monitor the progress of the injury. Short-latency intersegmental reflexes have been described for various respiratory muscles in animals. In humans, however, only short-latency reflex responses to phrenic nerve stimulation have been described. Here, we examined the reflex connections between intercostal afferents and scalene muscles in humans. Surface EMG recordings were made from scalene muscles bilaterally, in seven able-bodied participants and seven participants with motor- and sensory-complete cervical spinal cord injury (median 32 years postinjury, range 5 months to 44 years). We recorded the reflex responses produced by stimulation of the eighth or tenth left intercostal nerve. A short-latency (∼38 ms) inhibitory reflex was evident in able-bodied participants, in ipsilateral and contralateral scalene muscles. This bilateral intersegmental inhibitory reflex occurred in 46% of recordings at low stimulus intensities (at three times motor threshold). It was more frequent (in 75-85% of recordings) at higher stimulus intensities (six and nine times motor threshold), but onset latency (38 ± 9 ms, mean ± SD) and the size of inhibition (23 ± 10%) did not change with stimulus intensity. The reflex was absent in all participants with spinal cord injury. As the intercostal

  9. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse

    PubMed Central

    Daly, Donna M; Park, Sung Jin; Valinsky, William C; Beyak, Michael J

    2011-01-01

    Abstract Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity. PMID:21486762

  10. Trpv1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision.

    PubMed

    Banik, Ratan K; Brennan, Timothy J

    2009-01-01

    TrpV1, the receptor for capsaicin, contributes to nociception in animals but appears to be much more important for signaling increased behavioral sensitivity in the injured state. The current study examined the relationship between the marked reduction in heat hyperalgesia after incision in TrpV1 knockout (KO) mice and the activity of the nociceptors in these same mice. Also, the role of TrpV1 in spontaneous activity (SA) of afferents after incision was examined. Standard teased-fiber techniques were used to record from glabrous skin afferents from incised and control TrpV1 KO and C57Bl6 mice. The loss of TrpV1 had minimal effect on the responses of mechano-heat-sensitive C-fiber afferents in the normal and incised states. However, a different group of heat sensitive afferents, termed unclassified afferents, was sensitized to heat by incision and had markedly reduced sensitization in the TrpV1 KO mice. These unclassified afferents also developed SA after incision, and generally had a lower threshold temperature compared to unclassified afferents without SA. The rate of SA was inversely correlated to the threshold temperature for heat; afferents that exhibited a higher rate of SA had a lower heat threshold. The proportion of unclassified afferents with SA was also reduced in incised TrpV1 KO mice compared to incised C57Bl6 mice. We conclude that a distinct class of afferents outside the mechano-heat-sensitive afferent population likely contributes to heat hypersensitivity after plantar incision. KO of TrpV1 influences SA in these unclassified afferents in incised skin. SA in these afferents is perhaps a manifestation of heat sensitization.

  11. Encoding of tangential torque in responses of tactile afferent fibres innervating the fingerpad of the monkey

    PubMed Central

    Birznieks, Ingvars; Wheat, Heather E; Redmond, Stephen J; Salo, Lauren M; Lovell, Nigel H; Goodwin, Antony W

    2010-01-01

    Torsional loads are ubiquitous during everyday dextrous manipulations. We examined how information about torque is provided to the sensorimotor control system by populations of tactile afferents. Torsional loads of different magnitudes were applied in clockwise and anticlockwise directions to a standard central site on the fingertip. Three different background levels of contact (grip) force were used. The median nerve was exposed in anaesthetized monkeys and single unit responses recorded from 66 slowly adapting type-I (SA-I) and 31 fast adapting type-I (FA-I) afferents innervating the distal segments of the fingertips. Most afferents were excited by torque but some were suppressed. Responses of the majority of both afferent types were scaled by torque magnitude applied in one or other direction, with the majority of FA-I afferent responses and about half of SA-I afferent responses scaled in both directions. Torque direction affected responses in both afferent types, but more so for the SA-I afferents. Latencies of the first spike in FA-I afferent responses depended on the parameters of the torque. We used a Parzen window classifier to assess the capacity of the SA-I and FA-I afferent populations to discriminate, concurrently and in real-time, the three stimulus parameters, namely background normal force, torque magnitude and direction. Despite the potentially confounding interactions between stimulus parameters, both the SA-I and the FA-I populations could extract torque magnitude accurately. The FA-I afferents signalled torque magnitude earlier than did the SA-I afferents, but torque direction was extracted more rapidly and more accurately by the SA-I afferent population. PMID:20142274

  12. Stimulation of μ-opioid receptors dilates retinal arterioles by neuronal nitric oxide synthase-derived nitric oxide in rats.

    PubMed

    Someya, Eriko; Mori, Asami; Sakamoto, Kenji; Ishii, Kunio; Nakahara, Tsutomu

    2017-03-21

    Opioids contribute to the regulation of cerebral vascular tone. The purpose of this study was to examine the effects of herkinorin, a non-opioid μ-opioid receptor agonist derived from salvinorin A, on blood vessels in the rat retina and to investigate the mechanism underlying the herkinorin-induced retinal vasodilatory response. Ocular fundus images were captured using an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal arterioles in the fundus images. Both systemic blood pressure and heart rate were continuously recorded. Herkinorin increased the retinal arteriolar diameter without significantly changing mean blood pressure and heart rate. The retinal vasodilator response to herkinorin was almost completely prevented following treatment with naloxone, a nonselective opioid receptor antagonist and H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective μ-opioid receptor antagonist. N(ω)-nitro-L-arginine methyl ester, a nonselective nitric oxide (NO) synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, significantly attenuated the herkinorin-induced retinal vasodilator responses. In addition, N(ω)-propyl-L-arginine, an inhibitor of neuronal NO synthase, diminished the herkinorin-induced retinal vasodilator responses. Seven days after an intravitreal injection of N-methyl-d-aspartic acid, loss of inner retinal neurons and abolishment of the retinal vasodilator response to herkinorin were observed. These results suggest that herkinorin dilates rat retinal arterioles through stimulation of retinal μ-opioid receptors. The μ-opioid receptor-mediated retinal vasodilator response is likely mediated by NO generated by neuronal NO synthase. Retinal neurons play an important role in the retinal vasodilator mechanism involving μ-opioid receptors in rats.

  13. Endothelium-dependent vasodilation in myogenically active mouse skeletal muscle arterioles: role of EDH and K(+) channels.

    PubMed

    Potocnik, Simon J; McSherry, Iain; Ding, Hong; Murphy, Timothy V; Kotecha, Neela; Dora, Kim A; Yuill, Kathryn H; Triggle, Chris R; Hill, Michael A

    2009-07-01

    As smooth muscle cell (SMC) membrane potential (E(m)) is critical for vascular responsiveness, and arteriolar SMCs are depolarized at physiological intraluminal pressures, we hypothesized that myogenic tone impacts on dilation mediated by endothelium-derived hyperpolarization (EDH). Studies were performed on cannulated mouse cremaster arterioles [diameter, 33+/-2 microm (n=23) at 60 mmHg; SMC Em -34.6+/-1.2 mV (n=7)]. Myogenic activity was assessed as tone developed in response to intraluminal pressure. Functional observations were related to mRNA, protein expression, and anatomy. Acetylcholine concentration-response curves showed a modest shift following indomethacin (10 microM) and L-NAME (100 microM), although maximal vasodilation was achieved. Residual dilation was removed by apamin (1 microM) in combination with TRAM-34 (1 microM) or charybotoxin (0.1 microM), indicating the requirement of small (S) and intermediate (I) calcium-activated potassium channels (K(Ca)). Charybdotoxin, but not TRAM-34, caused vasoconstriction, presumably through the inhibition of SMC BK(Ca). Expression of SK3 and IK1 was confirmed by immunohistochemistry and polymerase chain reaction, while myoendothelial junctions were common, suggesting a high degree of cell coupling. Also consistent with a role for endothelial K(Ca) channels, acetylcholine increased endothelium [Ca(2 +)](i). Apamin and TRAM-34 similarly blocked EDH-mediated dilation at intraluminal pressures of 30 and 90 mmHg, suggesting that in mouse arterioles, SK(Ca -) and IK(Ca -) mediated mechanisms predominate and operate independently of physiological levels of myogenic activation.

  14. Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

    PubMed

    Banek, Christopher T; Knuepfer, Mark M; Foss, Jason D; Fiege, Jessica K; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W

    2016-12-01

    Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. © 2016 American Heart Association, Inc.

  15. Primary afferent depolarization of muscle afferents elicited by stimulation of joint afferents in cats with intact neuraxis and during reversible spinalization.

    PubMed

    Quevedo, J; Eguibar, J R; Jiménez, I; Schmidt, R F; Rudomin, P

    1993-11-01

    1. In the anesthetized and artificially ventilated cat, stimulation of the posterior articular nerve (PAN) with low strengths (1.2-1.4 x T) produced a small negative response (N1) in the cord dorsum of the lumbosacral spinal cord with a mean onset latency of 5.2 ms. Stronger stimuli (> 1.4 x T) produced two additional components (N2 and N3) with longer latencies (mean latencies 7.5 and 15.7 ms, respectively), usually followed by a slow positivity lasting 100-150 ms. With stimulus strengths above 10 x T there was in some experiments a delayed response (N4; mean latency 32 ms). 2. Activation of posterior knee joint nerve with single pulses and intensities producing N1 responses only, usually produced no dorsal root potentials (DRPs), or these were rather small. Stimulation with strengths producing N2 and N3 responses produced distinct DRPs. Trains of pulses were clearly more effective than single pulses in producing DRPs, even in the low-intensity range. 3. Cooling the thoracic spinal cord to block impulse conduction, increased the DRPs and the N3 responses produced by PAN stimulation without significantly affecting the N2 responses. Reversible spinalization also increased the DRPs produced by stimulation of cutaneous nerves. In contrast, the DRPs produced by stimulation of group I afferents from flexors were reduced. 4. Conditioning electrical stimulation of intermediate and high-threshold myelinated fibers in the PAN depressed the DRPs produced by stimulation of group I muscle and of cutaneous nerves. 5. Analysis of the intraspinal threshold changes of single Ia and Ib fibers has provided evidence that stimulation of intermediate and high threshold myelinated fibers in the posterior knee joint nerve inhibits the primary afferent depolarization (PAD) of Ia fibers, and may either produce PAD or inhibit the PAD in Ib fibers, in the same manner as stimulation of cutaneous nerves. In 7/16 group I fibers the inhibition of the PAD was increased during reversible

  16. The future of GI and liver research: editorial perspectives. IV. Visceral afferents: an update.

    PubMed

    Raybould, Helen E

    2003-06-01

    The number of articles published in American Journal of Physiology Gastrointestinal and Liver Physiology over the last 15 years on visceral afferents has increased dramatically. This reflects our growing ability to study the characteristics and function of visceral afferents and also the recognition of their importance in the maintenance of homeostasis and also in a number of pathophysiological conditions. However, there are several key unanswered questions concerning the function of visceral afferents that await further investigation.

  17. Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla.

    PubMed

    Hirvonen, Timo P; Minor, Lloyd B; Hullar, Timothy E; Carey, John P

    2005-02-01

    Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P < 0.001) on the treated side (early: 44.3 +/- 16.3; late: 33.9 +/- 13.2 spikes x s(-1)) than on the untreated side (54.9 +/- 16.8 spikes x s(-1)). Spontaneous rates of irregular and intermediate afferents did not change. The majority of treated afferents did not measurably respond to tilt or rotation (82% in the early group, 76% in the late group). Those that did respond had abnormally low sensitivities (P < 0.001). Treated canal units that responded to rotation had mean sensitivities only 5-7% of the values for untreated canal afferents. Treated otolith afferents had mean sensitivities 23-28% of the values for untreated otolith units. Sensitivity to externally applied galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.

  18. Corneal afferents differentially target thalamic- and parabrachial-projecting neurons in spinal trigeminal nucleus caudalis.

    PubMed

    Aicher, S A; Hermes, S M; Hegarty, D M

    2013-03-01

    Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal nucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Corneal afferents differentially target thalamic- and parabrachial-projecting neurons in trigeminal subnucleus caudalis

    PubMed Central

    Aicher, Sue A.; Hermes, Sam M.; Hegarty, Deborah M.

    2012-01-01

    Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal subnucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway. PMID:23201828

  20. Cold- and menthol-sensitive C afferents of cat urinary bladder

    PubMed Central

    Jiang, C H; Maziéres, L; Lindström, S

    2002-01-01

    Cold-sensitive C afferents of the urinary bladder were studied in adult cats anaesthetised with α-chloralose. The bladder was catheterised for fluid instillations and bladder pressure recordings. Pelvic nerve branches were stimulated electrically close to the bladder. Evoked afferent activity was recorded from dissected filaments of the ipsilateral S1-S2 dorsal roots. Responsive afferents were identified using the ‘marking technique', based on activity-dependent decrease in C fibre conduction velocity. Of 108 examined bladder C afferents, 14 were activated by innocuous cooling of the bladder wall. Their conduction velocities ranged from 0.6 to 1.7 ms−1 and their activity dependent decrease in conduction velocity was <10 %. All nine cold-sensitive afferents tested responded to menthol exposure. Cold-sensitive C afferents failed to respond to bladder filling with body-warm saline and to active bladder contractions. These characteristics indicate that the cold-sensitive C afferents of the bladder resemble cutaneous cold receptors rather than cold-sensitive mechanoreceptors or nociceptors. It is concluded that the bladder wall is endowed with cold receptors with unmyelinated C afferents in the pelvic nerves and that these afferents are responsible for the bladder cooling reflex. PMID:12181293

  1. Antidromic discharges of dorsal root afferents in the neonatal rat.

    PubMed

    Vinay, L; Brocard, F; Fellippa-Marques, S; Clarac, F

    1999-01-01

    Presynaptic inhibition of primary afferents can be evoked from at least three sources in the adult animal: 1) by stimulation of several supraspinal structures; 2) by spinal reflex action from sensory inputs; or 3) by the activity of spinal locomotor networks. The depolarisation in the intraspinal afferent terminals which is due, at least partly, to the activation of GABA(A) receptors may be large enough to reach firing threshold and evoke action potentials that are antidromically conducted into peripheral nerves. Little is known about the development of presynaptic inhibition and its supraspinal control during ontogeny. This article, reviewing recent experiments performed on the in vitro brainstem/spinal cord preparation of the neonatal rat, demonstrates that a similar organisation is present, to some extent, in the new-born rat. A spontaneous activity consisting of antidromic discharges can be recorded from lumbar dorsal roots. The discharges are generated by the underlying afferent terminal depolarizations reaching firing threshold. The number of antidromic action potentials increases significantly in saline solution with chloride concentration reduced to 50% of control. Bath application of the GABA(A) receptor antagonist, bicuculline (5-10 microM) blocks the antidromic discharges almost completely. Dorsal root discharges are therefore triggered by chloride-dependent GABA(A) receptor-mediated mechanisms; 1) activation of descending pathways by stimulation delivered to the ventral funiculus (VF) of the spinal cord at the C1 level; 2) activation of sensory inputs by stimulation of a neighbouring dorsal root; or 3) pharmacological activation of the central pattern generators for locomotion evokes antidromic discharges in dorsal roots. VF stimulation also inhibited the response to dorsal root stimulation. The time course of this inhibition overlapped with that of the dorsal root discharge suggesting that part of the inhibition of the monosynaptic reflex may be

  2. Kv1 channels and neural processing in vestibular calyx afferents

    PubMed Central

    Meredith, Frances L.; Kirk, Matthew E.; Rennie, Katherine J.

    2015-01-01

    Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K+ channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K+ channels could help alleviate vestibular dysfunction on earth and in space. PMID:26082693

  3. Heat pulse excitability of vestibular hair cells and afferent neurons

    PubMed Central

    Brichta, Alan M.; Tabatabaee, Hessam; Boutros, Peter J.; Ahn, JoongHo; Della Santina, Charles C.; Poppi, Lauren A.; Lim, Rebecca

    2016-01-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at −68 mV and in 67% of hair cells at −60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability. PMID:27226448

  4. Purinergic signaling in cochleovestibular hair cells and afferent neurons

    PubMed Central

    Dulon, Didier

    2010-01-01

    Purinergic signaling in the mammalian cochleovestibular hair cells and afferent neurons is reviewed. The scope includes P2 and P1 receptors in the inner hair cells (IHCs) of the cochlea, the type I spiral ganglion neurons (SGNs) that convey auditory signals from IHCs, the vestibular hair cells (VHCs) in the vestibular end organs (macula in the otolith organs and crista in the semicircular canals), and the vestibular ganglion neurons (VGNs) that transmit postural and rotatory information from VHCs. Various subtypes of P2X ionotropic receptors are expressed in IHCs as well as P2Y metabotropic receptors that mobilize intracellular calcium. Their functional roles still remain speculative, but adenosine 5′-triphosphate (ATP) could regulate the spontaneous activity of the hair cells during development and the receptor potentials of mature hair cells during sound stimulation. In SGNs, P2Y metabotropic receptors activate a nonspecific cation conductance that is permeable to large cations as NMDG+ and TEA+. Remarkably, this depolarizing nonspecific conductance in SGNs can also be activated by other metabotropic processes evoked by acetylcholine and tachykinin. The molecular nature and the role of this depolarizing channel are unknown, but its electrophysiological properties suggest that it could lie within the transient receptor potential channel family and could regulate the firing properties of the afferent neurons. Studies on the vestibular partition (VHC and VGN) are sparse but have also shown the expression of P2X and P2Y receptors. There is still little evidence of functional P1 (adenosine) receptors in the afferent system of the inner ear. PMID:20806012

  5. Directional sensitivity of hair cell afferents in the Octopus statocyst.

    PubMed

    Budelmann, B U; Williamson, R

    1994-02-01

    Changes in threshold sensitivity of hair cell afferents of the macula and crista of the Octopus statocyst were analyzed when the hair cells were stimulated with sinusoidal water movements from different directions. The experiments indicate that cephalopod statocyst hair cells are directionally sensitive in a way that is similar to the responses of the hair cells of the vertebrate vestibular and lateral line systems, with the amplitude of the response changing according to the cosine of the angle by which the direction of the stimulus (the deflection of the ciliary bundle) deviates from the direction of the hair cell's morphological polarization.

  6. AAS Career Services

    NASA Astrophysics Data System (ADS)

    Marvel, Kevin B.

    2012-08-01

    The American Astronomical Society provides substantial programs in the area of Career Services.Motivated by the Society's mission to enhance and share humanity's understanding of the Universe, the AAS provides a central resource for advertising positions, interviewing opportunities at its annual winter meeting and information, workshops and networks to enable astronomers to find employment.The programs of the Society in this area are overseen by an active committee on employment and the AAS Council itself.Additional resources that help characterize the field, its growth and facts about employment such as salaries and type of jobs available are regularly summarized and reported on by the American Institute of Physics.

  7. Does glaucoma medication influence the diameter of the retinal arteriole in the human eye? (A pilot study using the retinal vessel analyser).

    PubMed

    Kóthy, P; Holló, G

    2001-01-01

    To investigate the potential in vivo influence of different topical glaucoma medications on the diameter of the retinal arterioles of healthy volunteers and glaucoma patients. The diameter of one pre-selected retinal arteriole per eye was measured using the Retinal Vessel Analyser (RVA), an instrument developed for non-invasive clinical measurement of the diameter of the main retinal vessels. The instrument contains a video system, and the integrated software recognises the boundaries of the retinal vessels by detecting their light-transmission profile. The vessel diameter (in arbitrary units) is plotted against time (seconds) on a separate display screen. In Study I the vessel diameter was measured in 12 eyes of six healthy volunteers (age 21-26 years, mean age 24.0 years) on six occasions each separated by 14 days. In a double-masked fashion, each subject's right eye was treated with one of 5 glaucoma medications (brinzolamide 1%, timolol 0.5%, betaxolol 0.5%, brimonidine 0.2% or latanoprost 0.005%) and the left eye always received balanced salt solution. In Study II, one randomly selected eye of 16 patients (age 50-79 years, mean age 65.2 years) suffering from primary open-angle glaucoma controlled with topical monotherapy was investigated, in an unmasked fashion. Four patients were on betaxolol 0.5% treatment, six subjects were receiving non-selective topical beta receptor blockers and six subjects were being treated with once daily latanoprost 0.005%. The coefficient of variation for the arteriole diameter in the healthy volunteers was less than 12% in each case. No significant post-treatment change of the diameter of the pre-selected arteriole was found for any topical medication investigated, either in the healthy volunteers (Study I) or in the patients suffering from glaucoma (Study II) (p>0.05, paired t-test). In addition, in Study I no difference was observed in the alteration of the arteriole diameter between the baseline and the hour 2 measurements when

  8. Transfection of CYP4A1 cDNA decreases diameter and increases responsiveness of gracilis muscle arterioles to constrictor stimuli.

    PubMed

    Zhang, Fan; Wang, Mong-Heng; Wang, Ji-Shi; Zand, Barbara; Gopal, V Raj; Falck, John R; Laniado-Schwartzman, Michal; Nasjletti, Alberto

    2004-09-01

    Cytochrome P-450-4A1 (CYP4A1) is an omega-hydroxylase that catalyzes the metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE). The goal of this study was to determine the vasomotor consequences of vascular overexpression of CYP4A1. Isolated rat gracilis muscle arterioles transfected ex vivo with an expression plasmid containing CYP4A1 cDNA expressed more CYP4A protein than vessels transfected with the control plasmid. In arterioles pressurized to 80 mmHg, the internal diameter of vessels transfected with CYP4A1 cDNA (55 +/- 3 microm) was surpassed (P < 0.05) by that of vessels transfected with control plasmid (97 +/- 4 microm). Treatment with a CYP4A inhibitor (N-methylsulfonyl-12,12-dibromododec-11-enamide; DDMS) or with an antagonist of 20-HETE actions [20-hydroxyeicosa-6(Z),15(Z)-dienoic acid; 20-HEDE] elicited robust dilation of arterioles transfected with CYP4A1 cDNA, whereas the treatment had little or no effect in vessels transfected with control plasmid. Examination of the intraluminal pressure-internal diameter relationship revealed that pressure increments over the range of 40-100 mmHg elicited a more intense (P < 0.05) myogenic constrictor response in arterioles transfected with CYP4A1 cDNA than in those with control plasmid. Arterioles transfected with CYP4A1 cDNA also displayed enhanced sensitivity to the constrictor action of phenylephrine. Treatment with DDMS or 20-HEDE greatly attenuated the constrictor responsiveness to both constrictor stimuli in vessels overexpressing CYP4A1, whereas the treatment had much less effect in control vessels. These data suggest that CYP4A1 overexpression promotes constriction of gracilis muscle arterioles by intensifying the responsiveness of vascular smooth muscle to constrictor stimuli. This effect of CYP4A1 overexpression appears to be mediated by a CYP4A1 product.

  9. Neuropeptide Y-mediated sex- and afferent-specific neurotransmissions contribute to sexual dimorphism of baroreflex afferent function

    PubMed Central

    He, Jian-Li; Yuan, Mei; Zhao, Miao; Wang, Jian-Xin; He, Jian; Wang, Lu-Qi; Guo, Xin-Jing; Zuo, Meng; Zhao, Shu-Yang; Ma, Mei-Na; Li, Jun-Nan; Shou, Weinian; Qiao, Guo-Fen; Li, Bai-Yan

    2016-01-01

    Background Molecular and cellular mechanisms of neuropeptide-Y (NPY)-mediated gender-difference in blood pressure (BP) regulation are largely unknown. Methods Baroreceptor sensitivity (BRS) was evaluated by measuring the response of BP to phenylephrine/nitroprusside. Serum NPY concentration was determined using ELISA. The mRNA and protein expression of NPY receptors were assessed in tissue and single-cell by RT-PCR, immunoblot, and immunohistochemistry. NPY was injected into the nodose while arterial pressure was monitored. Electrophysiological recordings were performed on nodose neurons from rats by patch-clamp technique. Results The BRS was higher in female than male and ovariectomized rats, while serum NPY concentration was similar among groups. The sex-difference was detected in Y1R, not Y2R protein expression, however, both were upregulated upon ovariectomy and canceled by estrogen replacement. Immunostaining confirmed Y1R and Y2R expression in myelinated and unmyelinated afferents. Single-cell PCR demonstrated that Y1R expression/distribution was identical between A- and C-types, whereas, expressed level of Y2R was ∼15 and ∼7 folds higher in Ah- and C-types than A-types despite similar distribution. Activation of Y1R in nodose elevated BP, while activation of Y2R did the opposite. Activation of Y1R did not alter action potential duration (APD) of A-types, but activation of Y2R- and Y1R/Y2R in Ah- and C-types frequency-dependently prolonged APD. N-type ICa was reduced in A-, Ah- and C-types when either Y1R, Y2R, or both were activated. The sex-difference in Y1R expression was also observed in NTS. Conclusions Sex- and afferent-specific expression of Neuropeptide-Y receptors in baroreflex afferent pathway may contribute to sexual-dimorphic neurocontrol of BP regulation. PMID:27623075

  10. Facilitated diffusion of angiotensin II from perivascular interstitium to AT1 receptors of the arteriole. A regulating step in vasoconstriction.

    PubMed

    Schalekamp, Maarten A D H; Danser, A H Jan

    2011-05-01

    A kinetic model for the binding of angiotensin (Ang) II to AT1 receptors (AT1R) in arterioles in vivo did suggest a novel mechanism of stimulus amplification. To further clarify the role of this mechanism in the functioning of the local renin-angiotensin systems, as opposed to circulating Ang II. The model was refined in order to account for geometric characteristics of the vascular smooth muscle (VSM) cells in arterioles with a single VSM cell layer. Results show that, unlike experiments in vitro, the graph of AT1R occupancy, that is, [Rec(occ)]/[Rec(total)] where [Rec(total)]=[Rec(occ)]+[Rec(free)], as a function of log [Ang II], is shifted to the left at higher [Rec(total)]. This leads to the concept of association rate amplification (ASRA) and facilitated Ang II diffusion. Considering that abluminal Ang II has to cross a diffusion fluid-barrier 1-10 times the glycocalyx to reach VSM AT1R, it appears that the ASRA factor is 1500 to 150 respectively, whereas more than 90% of Ang II is captured, at 10% occupancy, and with [Ang II] as low as 10(-15)-10(-14) mol/ml. Due to the presence of endothelium, intraluminal [Ang II] needs to be 20-30 times higher. ASRA favors a low [Ang II] threshold for AT1R stimulation, but it also favors a flat stimulus/response curve by promoting receptor-mediated endocytosis and receptor downregulation. The model predicts that, in small resistance vessels, abluminal rather than intraluminal Ang II is important for maintaining vasoconstrictor tone. ASRA minimizes the overflow of de-novo generated tissue Ang II into the circulation. It explains why Ang II acts at levels far below K(D), why AT1R blockers are effective in hypertension even when [Ang II] is low, and why the constrictor action of Ang II appears so much suppressed by sodium depletion. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

  11. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  12. Classification of muscle spindle afferents innervating the masseter muscle in rats.

    PubMed

    Masri, Radi; Ro, Jin Y; Dessem, Dean; Capra, Norman

    2006-09-01

    Taylor et al. [Taylor, A., Durbaba, R., Rodgers, J.F., 1992a. The classification of afferents from muscle spindles of the jaw-closing muscles of the cat. J Physiol 456, 609-628] developed a method to classify muscle spindle afferents using succinylcholine (Sch) and ramp and hold stretches. They demonstrated that cat jaw muscle spindle afferents show high proportion of intermediate responses to ramp and hold jaw stretch. Together with observations on the responses to Sch their data suggests that the majority of jaw muscle spindle afferents are influenced by a combination of nuclear bag(2) and nuclear chain fibres. Relatively few are influenced solely by nuclear bag(1) fibres. The purpose of this study was to categorize jaw muscle spindle afferent in rodents in response to ramp and hold stretches. Several measures were used to classify spindle afferents including (1) conduction velocity, (2) coefficient of variation (C.V.) of the interspike interval during jaw opening, and (3) the dynamic sensitivity and the initial discharge of spindle afferents before and after succinylcholine infusion (Sch, 100mg/kg, i.v.). Consistent with observations in the cat jaw muscles, the distribution of the conduction velocity and the C.V. of Vmes masseter afferents were unimodal. Therefore, these parameters were of little value in functional classification of spindle innervation. Succinylcholine injection either markedly increased the dynamic sensitivity or produced no change in Vmes afferents. Unlike cat jaw muscle spindle afferents, the effect of Sch on the initial discharge was not clearly separable from those responding or not responding to Sch. These results suggest that rat jaw muscle spindle afferents, have physiological properties that are primarily intermediate in nature and are likely to reflect a predominance of influence from nuclear bag(2) and chain fibres. However, the distinction between bag(2) and chain fibres influences is not as clearly defined in the rat compared to

  13. Use of tactile afferent information in sequential finger movements.

    PubMed

    Gordon, A M; Soechting, J F

    1995-01-01

    We have investigated how tactile afferent information contributes to the generation of sequences of skilled finger movements by anesthetizing the right index fingers of experienced typists. Subjects were asked to type phrases in which the right index finger was used only once every seven to 12 keypresses. The time at which each key was depressed was recorded with a digital timer, and the translational and rotational motion of the fingers and wrist of the right hand were recorded optoelectronically from the location of reflective markers placed on the fingers. Midway through the experiment, a local anesthetic was injected at the base of the distal phalange of the right index finger. Following digital anesthesia, error rates increased considerably, mainly due to the diminished accuracy of movements of the anesthetized finger. The typing intervals following keypresses with the anesthetized fingertip were unaffected by the removal of tactile information. When errors occurred during control trials, the intervals immediately following the errors were greatly prolonged. However, errors produced with the anesthetized right index finger did not influence the timing of subsequent keypresses, implying that lack of tactile cues affected error recognition. The movement patterns during keypresses were similar before and after digital anesthesia for some subjects, while a less pronounced flexion-extension movement was seen in other subjects. The results suggest that tactile afferent information is not essential for initiating movement segments in a sequence. Rather, they emphasize the importance of this information for ensuring movement accuracy and for detecting errors.

  14. Cross-Modal Calibration of Vestibular Afference for Human Balance

    PubMed Central

    Héroux, Martin E; Law, Tammy C. Y.; Fitzpatrick, Richard C.; Blouin, Jean-Sébastien

    2015-01-01

    To determine how the vestibular sense controls balance, we used instantaneous head angular velocity to drive a galvanic vestibular stimulus so that afference would signal that head movement was faster or slower than actual. In effect, this changed vestibular afferent gain. This increased sway 4-fold when subjects (N = 8) stood without vision. However, after a 240 s conditioning period with stable balance achieved through reliable visual or somatosensory cues, sway returned to normal. An equivalent galvanic stimulus unrelated to sway (not driven by head motion) was equally destabilising but in this situation the conditioning period of stable balance did not reduce sway. Reflex muscle responses evoked by an independent, higher bandwidth vestibular stimulus were initially reduced in amplitude by the galvanic stimulus but returned to normal levels after the conditioning period, contrary to predictions that they would decrease after adaptation to increased sensory gain and increase after adaptation to decreased sensory gain. We conclude that an erroneous vestibular signal of head motion during standing has profound effects on balance control. If it is unrelated to current head motion, the CNS has no immediate mechanism of ignoring the vestibular signal to reduce its influence on destabilising balance. This result is inconsistent with sensory reweighting based on disturbances. The increase in sway with increased sensory gain is also inconsistent with a simple feedback model of vestibular reflex action. Thus, we propose that recalibration of a forward sensory model best explains the reinterpretation of an altered reafferent signal of head motion during stable balance. PMID:25894558

  15. A quantitative study of cochlear afferent axons in birds.

    PubMed

    Köppl, C; Wegscheider, A; Gleich, O; Manley, G A

    2000-01-01

    This paper is a comparative study of auditory-nerve morphology in birds. The chicken (Gallus gallus), the emu (Dromaius novaehollandiae) and the starling (Sturnus vulgaris) were chosen as unspecialised birds that have already been used in auditory research. The data are discussed in comparison to a similar earlier study on the barn owl, a bird with highly specialised hearing, in an attempt to separate general avian patterns from species specialisations. Average numbers of afferent fibres from 8775 (starling) to 12¿ omitted¿406 (chicken) were counted, excluding fibres to the lagenar macula. The number of fibres representing different frequency ranges showed broad maxima in the chicken and emu, corresponding to hearing ranges of best sensitivity and/or particular behavioural relevance. Mean axon diameters were around 2 microm in the chicken and starling, and around 3 microm in the emu. Virtually all auditory afferents were myelinated. The mean thickness of the myelin sheaths was between 0.33 microm (starling) and 0.4 microm (emu). There was a consistent pattern in the diameters of axons deriving from different regions. Axons from very basal, i.e. highest-frequency, parts of the basilar papilla were always the smallest. In the emu and the chicken, axons from the middle papillar regions were, in addition, larger than axons innervating apical regions.

  16. Interactions between visceral afferent signaling and stimulus processing

    PubMed Central

    Critchley, Hugo D.; Garfinkel, Sarah N.

    2015-01-01

    Visceral afferent signals to the brain influence thoughts, feelings and behavior. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated) physiological arousal to emotional, social and motivational behaviors, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain's representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed. PMID:26379481

  17. Anatomy and physiology of the afferent visual system.

    PubMed

    Prasad, Sashank; Galetta, Steven L

    2011-01-01

    The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Microsecond-Scale Timing Precision in Rodent Trigeminal Primary Afferents

    PubMed Central

    Bale, Michael R.; Campagner, Dario; Erskine, Andrew

    2015-01-01

    Communication in the nervous system occurs by spikes: the timing precision with which spikes are fired is a fundamental limit on neural information processing. In sensory systems, spike-timing precision is constrained by first-order neurons. We found that spike-timing precision of trigeminal primary afferents in rats and mice is limited both by stimulus speed and by electrophysiological sampling rate. High-speed video of behaving mice revealed whisker velocities of at least 17,000°/s, so we delivered an ultrafast “ping” (>50,000°/s) to single whiskers and sampled primary afferent activity at 500 kHz. Median spike jitter was 17.4 μs; 29% of neurons had spike jitter < 10 μs. These results indicate that the input stage of the trigeminal pathway has extraordinary spike-timing precision and very high potential information capacity. This timing precision ranks among the highest in biology. PMID:25878266

  19. AAS Oral History Project

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Holbrook, Jarita; AAS Oral History Team

    2016-06-01

    Now in its fourth year, the AAS Oral History Project has interviewed over 80 astronomers from all over the world. Led by the AAS Historical Astronomy Division (HAD) and partially funded by the American Institute of Physics Niels Bohr Library and ongoing support from the AAS, volunteers have collected oral histories from astronomers at professional meetings starting in 2015, including AAS, DPS, and the IAU general assembly. Each interview lasts one and a half to two hours and focuses on interviewees’ personal and professional lives. Questions include those about one’s family, childhood, strong influences on one’s scientific career, career path, successes and challenges, perspectives on how astronomy is changing as a field, and advice to the next generation. Each interview is audio recorded and transcribed, the content of which is checked with each interviewee. Once complete, interview transcripts are posted online as part of a larger oral history library at https://www.aip.org/history-programs/niels-bohr-library/oral-histories. Future analysis will reveal a rich story of astronomers and will help the community address issues of diversity, controversies, and the changing landscape of science. We are still recruiting individuals to be interviewed from all stages of career from undergraduate students to retired and emeritus astronomers. Contact Jarita Holbrook to schedule an interview or to find out more information about the project (astroholbrook@gmail.com). Also, contact Jarita Holbrook if you would like to become an interviewer for the project.

  20. Role of the kallikrein-kinin system in Ang-(1-7)-induced vasodilation in mesenteric arterioles of Wistar rats studied in vivo-in situ.

    PubMed

    Marangoni, Rossana Anderson; Carmona, Adriana Karaoglanovic; Passaglia, Rita Cássia A Tostes; Nigro, Dorothy; Fortes, Zuleica Bruno; de Carvalho, Maria Helena Catelli

    2006-07-01

    Angiotensin-(1-7) [Ang-(1-7)], exerts a variety of actions in the cardiovascular system, with an important effect being vasodilation. In this work, we investigated the relationship between the vasodilatory activity of Ang-(1-7) and the kallikrein-kinin system. Intravital microscopy was used to study the vasodilation caused by Ang-(1-7) in the mesenteric vascular bed of anesthetized Wistar rats. The topical application of Ang-(1-7) caused vasodilation of mesenteric arterioles that was reduced by A-779, JE 049 and peptidase inhibitors (aprotinin, SBTI, PKSI 527, E-64, PMSF). These results indicated that the vasodilation induced by Ang-(1-7) in the mesenteric arterioles of Wistar rats was heavily dependent on the activation of kallikrein and subsequent kinin formation.

  1. Persistence of PAD and presynaptic inhibition of muscle spindle afferents after peripheral nerve crush.

    PubMed

    Enríquez-Denton, M; Manjarrez, E; Rudomin, P

    2004-11-19

    Two to twelve weeks after crushing a muscle nerve, still before the damaged afferents reinnervate the muscle receptors, conditioning stimulation of group I fibers from flexor muscles depolarizes the damaged afferents [M. Enriquez, I. Jimenez, P. Rudomin, Changes in PAD patterns of group I muscle afferents after a peripheral nerve crush. Exp. Brain Res., 107 (1996), 405-420]. It is not known, however, if this primary afferent depolarization (PAD) is indeed related to presynaptic inhibition. We now show in the cat that 2-12 weeks after crushing the medial gastrocnemius nerve (MG), conditioning stimulation of group I fibers from flexors increases the excitability of the intraspinal terminals of both the intact lateral gastrocnemius plus soleus (LGS) and of the previously damaged MG fibers ending in the motor pool, because of PAD. The PAD is associated with the depression of the pre- and postsynaptic components of the extracellular field potentials (EFPs) evoked in the motor pool by stimulation of either the intact LGS or of the previously damaged MG nerves. These observations indicate, in contrast to what has been reported for crushed cutaneous afferents [K.W. Horch, J.W. Lisney, Changes in primary afferent depolarization of sensory neurones during peripheral nerve regeneration in the cat, J. Physiol., 313 (1981), 287-299], that shortly after damaging their peripheral axons, the synaptic efficacy of group I spindle afferents remains under central control. Presynaptic inhibitory mechanisms could be utilized to adjust the central actions of muscle afferents not fully recovered from peripheral lesions.

  2. Primary afferent depolarization and inhibory interactions in spinal cord of the stingray, Dasyatis sabina.

    PubMed

    Rudomín, P; Leonard, R B; Willis, W D

    1978-01-01

    1. Excitability changes in primary afferents and inhibitory interactions in evoked spinal cord activity were investigated in unanesthetized stingrays (Dasyatis subina) with high cervical spinal transections. 2. Primary afferent excitability increases following a conditioning stimulus to an adjacent segmental nerve were demonstrated with the Wall (31) technique. 3. Stimulation of A-alpha,beta and A-delta afferent fibers produced excitability increases in both A-alpha,beta and delta-fibers of the adjacent segment. 4. The excitability increase had a latency of about 10 ms, it peaked around 25 ms, and the change lasted more than 100 ms. 5. The central afferent volley in A-alpha,beta fibers and the N1- and late negative waves due to postsynaptic activity of dorsal horn interneurons were reduced by conditioning volleys in adjacent afferent nerves. The time course of the inhibition paralleled that of the excitability increases in afferent terminal arborizations, suggesting that the depression of postsynaptic activity is, at least in part, due to presynaptic inhibition. 6. Reduction of evoked discharges and excitatory postsynaptic potentials was observed in recordings from interneurons with a time course similar to that of the primary afferent depolarization (PAD). 7. Conditioning volleys in afferents of adjacent peripheral nerves produced facilitation or inhibition of segmental reflexes.

  3. Primary afferent depolarization and flexion reflexes produced by radiant heat stimulation of the skin.

    PubMed

    Burke, R E; Rudomin, P; Vyklický, L; Zajac, F E

    1971-02-01

    1. The reflex effects of pulses of intense radiant heat applied to the skin of the central plantar pad have been studied in unanaesthetized (decerebrate) spinal cats.2. Pad heat pulses produced flexion of the ipsilateral hind limb and increased ipsilateral flexor monosynaptic reflexes, due to post-synaptic excitation of flexor alpha motoneurones. These effects were accompanied by reduction of extensor monosynaptic reflexes and post-synaptic inhibition of extensor motoneurones.3. Ipsilateral (and contralateral) pad heat pulses consistently evoked negative dorsal root potentials (DRPs) as well as increased excitability of both cutaneous and group Ib muscle afferent terminals. The excitability of group Ia afferents was sometimes also increased during pad heat pulses, but to a lesser extent.4. Pad heat pulses produced negative DRPs in preparations in which positive DRP components could be demonstrated following electrical stimulation of both skin and muscle nerves.5. The motor and primary afferent effects of heat pulses always accompanied one another, beginning after the pad surface temperature had reached rather high levels (usually 48-55 degrees C).6. Negative DRPs increased excitability of cutaneous and group Ib afferents, and motoneurone activation produced by pad heat pulses was essentially unmodified when conduction in large myelinated afferents from the central plantar pad was blocked by cooling the posterior tibial nerve trunk.7. It is concluded that adequate noxious activation of cutaneous afferents of small diameter produces primary afferent depolarization in a variety of large diameter afferent fibres, as well as post-synaptic effects in alpha motoneurones.

  4. Primary afferent depolarization and flexion reflexes produced by radiant heat stimulation of the skin

    PubMed Central

    Burke, R. E.; Rudomin, P.; Vyklický, L.; Zajac, F. E.

    1971-01-01

    1. The reflex effects of pulses of intense radiant heat applied to the skin of the central plantar pad have been studied in unanaesthetized (decerebrate) spinal cats. 2. Pad heat pulses produced flexion of the ipsilateral hind limb and increased ipsilateral flexor monosynaptic reflexes, due to post-synaptic excitation of flexor alpha motoneurones. These effects were accompanied by reduction of extensor monosynaptic reflexes and post-synaptic inhibition of extensor motoneurones. 3. Ipsilateral (and contralateral) pad heat pulses consistently evoked negative dorsal root potentials (DRPs) as well as increased excitability of both cutaneous and group Ib muscle afferent terminals. The excitability of group Ia afferents was sometimes also increased during pad heat pulses, but to a lesser extent. 4. Pad heat pulses produced negative DRPs in preparations in which positive DRP components could be demonstrated following electrical stimulation of both skin and muscle nerves. 5. The motor and primary afferent effects of heat pulses always accompanied one another, beginning after the pad surface temperature had reached rather high levels (usually 48-55° C). 6. Negative DRPs increased excitability of cutaneous and group Ib afferents, and motoneurone activation produced by pad heat pulses was essentially unmodified when conduction in large myelinated afferents from the central plantar pad was blocked by cooling the posterior tibial nerve trunk. 7. It is concluded that adequate noxious activation of cutaneous afferents of small diameter produces primary afferent depolarization in a variety of large diameter afferent fibres, as well as post-synaptic effects in alpha motoneurones. PMID:5575337

  5. Early postnatal development of GABAergic presynaptic inhibition of Ia proprioceptive afferent connections in mouse spinal cord.

    PubMed

    Sonner, Patrick M; Ladle, David R

    2013-04-01

    Sensory feedback is critical for normal locomotion and adaptation to external perturbations during movement. Feedback provided by group Ia afferents influences motor output both directly through monosynaptic connections and indirectly through spinal interneuronal circuits. For example, the circuit responsible for reciprocal inhibition, which acts to prevent co-contraction of antagonist flexor and extensor muscles, is driven by Ia afferent feedback. Additionally, circuits mediating presynaptic inhibition can limit Ia afferent synaptic transmission onto central neuronal targets in a task-specific manner. These circuits can also be activated by stimulation of proprioceptive afferents. Rodent locomotion rapidly matures during postnatal development; therefore, we assayed the functional status of reciprocal and presynaptic inhibitory circuits of mice at birth and compared responses with observations made after 1 wk of postnatal development. Using extracellular physiological techniques from isolated and hemisected spinal cord preparations, we demonstrate that Ia afferent-evoked reciprocal inhibition is as effective at blocking antagonist motor neuron activation at birth as at 1 wk postnatally. In contrast, at birth conditioning stimulation of muscle nerve afferents failed to evoke presynaptic inhibition sufficient to block functional transmission at synapses between Ia afferents and motor neurons, even though dorsal root potentials could be evoked by stimulating the neighboring dorsal root. Presynaptic inhibition at this synapse was readily observed, however, at the end of the first postnatal week. These results indicate Ia afferent feedback from the periphery to central spinal circuits is only weakly gated at birth, which may provide enhanced sensitivity to peripheral feedback during early postnatal experiences.

  6. Symmetry recovery of cell-free layer after bifurcations of small arterioles in reduced flow conditions: effect of RBC aggregation.

    PubMed

    Ng, Yan Cheng; Namgung, Bumseok; Tien, Sim Leng; Leo, Hwa Liang; Kim, Sangho

    2016-08-01

    Heterogeneous distribution of red blood cells (RBCs) in downstream vessels of arteriolar bifurcations can be promoted by an asymmetric formation of cell-free layer (CFL) in upstream vessels. Consequently, the CFL widths in subsequent downstream vessels become an important determinant for tissue oxygenation (O2) and vascular tone change by varying nitric oxide (NO) availability. To extend our previous understanding on the formation of CFL in arteriolar bifurcations, this study investigated the formation of CFL widths from 2 to 6 vessel-diameter (2D-6D) downstream of arteriolar bifurcations in the rat cremaster muscle (D = 51.5 ± 1.3 μm). As the CFL widths are highly influenced by RBC aggregation, the degree of aggregation was adjusted to simulate levels seen during physiological and pathological states. Our in vivo experimental results showed that the asymmetry of CFL widths persists along downstream vessels up to 6D from the bifurcating point. Moreover, elevated levels of RBC aggregation appeared to retard the recovery of CFL width symmetry. The required length of complete symmetry recovery was estimated to be greater than 11D under reduced flow conditions, which is relatively longer than interbifurcation distances of arterioles for vessel diameter of ∼50 μm. In addition, our numerical prediction showed that the persistent asymmetry of CFL widths could potentially result in a heterogeneous vasoactivity over the entire arteriolar network in such abnormal flow conditions.

  7. MMP-2 Is Mainly Expressed in Arterioles and Contributes to Cerebral Vascular Remodeling Associated with TGF-β1 Signaling.

    PubMed

    Hua, Ye; Zhang, Weifeng; Xie, Zhenying; Xu, Nanfei; Lu, Yunnan

    2016-07-01

    There is increasing evidence to suggest that matrix metalloproteinases (MMPs) play a crucial role in vascular remodeling. It has been reported that hypoxia stimulated MMP-9 expression in brain endothelial cells and MMP-9 plays an important role in cerebral vascular remodeling. However, little is known about MMP-2 in the cerebral vessels remodeling. Herein, the aim of this study is to examine the class of vessel and cell type expressing MMP-2 in cerebral vessels and to investigate its potential role in vascular remodeling. In the present study, dual-immunofluorescence assay showed that MMP-2 was mainly expressed in arterioles. In addition, we found that MMP-2 expression in cerebral vessels was derived from endothelial cells, not astrocyte cells. Notably, in the normoxic central nervous system (CNS), there was no effect on vascular development, integrity, or endothelial proliferation when MMP-2 was knocked out, but lack of MMP-2 led to defective arteriolar remodeling and associated with transforming growth factor β1 (TGF-β1) signaling in CNS. Moreover, blocking TGF-β with SB431542, a specific TGF-β inhibitor, significantly reduced the messenger RNA (mRNA) and protein expression levels of MMP-2 in human umbilical vein endothelial cells (HUVECs). Our findings reveal that the level of MMP-2 is high in arteriolar endothelial cells and demonstrate a novel connection between MMP-2 and TGF-β1 signaling in cerebral vascular remodeling.

  8. Numerical simulation of red blood cell behavior in a stenosed arteriole using the immersed boundary-lattice Boltzmann method.

    PubMed

    Vahidkhah, Koohyar; Fatouraee, Nasser

    2012-02-01

    Because of their deformability and tendency to form aggregates, red blood cells (RBCs) immensely affect the hydrodynamic properties of blood flow in microcirculation. In this paper, RBCs' two-dimensional deformation and motion in Poiseuille flow and in a stenosed arteriole is numerically investigated by the immersed boundary-lattice Boltzmann method. The RBCs are modeled as suspended capsules of fluid in plasma flow. A neo-Hookean elastic model with bending resistance is utilized for the RBC membrane. Also, the suspending plasma is modeled as an incompressible Newtonian fluid. To take the effects of aggregation and dissociation of RBCs into account, intercellular interaction is modeled by the Morse potential. The effects of essential parameters namely, mechanical resistance of the RBC membrane, plasma viscous forces, and cell membrane adhesion strength on RBC behavior are presented. Motions and deformations of RBCs in a stenosis and the effects of the stenosed zone on the behavior of cell aggregates were also simulated and analyzed in this study.

  9. Relationship between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles evaluated noninvasively by scanning laser Doppler flowmetry.

    PubMed

    Rizzoni, Damiano; Porteri, Enzo; Duse, Sarah; De Ciuceis, Carolina; Rosei, Claudia Agabiti; La Boria, Elisa; Semeraro, Francesco; Costagliola, Ciro; Sebastiani, Adolfo; Danzi, Paola; Tiberio, Guido A M; Giulini, Stefano M; Docchio, Franco; Sansoni, Giovanna; Sarkar, Annamaria; Rosei, Enrico Agabiti

    2012-06-01

    Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach. We investigated 40 individuals and patients, 24 of them were hypertensive patients and 16 normotensive individuals. All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and media-to-lumen ratio was measured. In addition, an evaluation of wall-to-lumen ratio of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles (r = 0.76, P < 0.001; P < 0.001, r(2) = 0.57). A noninvasive and easily repeatable procedure (intraobserver and interobserver variation coefficient <13%) such as an evaluation of the arterioles in the fundus oculi by SLDF may provide similar information regarding microvascular morphology compared with an invasive, accurate and prognostically relevant micromyographic measurement of media-to-lumen ratio of subcutaneous small arteries.

  10. Presynaptic inhibition of muscle spindle and tendon organ afferents in the mammalian spinal cord.

    PubMed

    Rudomin, P

    1990-12-01

    More than 30 years ago, Frank and Fuortes proposed that the synaptic effectiveness of muscle spindle afferents associated with spinal motoneurones could be diminished by the activation of nerves from flexor muscles. Since that time, research has focused on disclosing the mode of operation and the spinal pathways involved in this presynaptic inhibitory control. Initially, it was assumed that the same last-order interneurones mediated presynaptic inhibition of both muscle spindle and tendon organ afferent fibres. More recent evidence indicates that the synaptic effectiveness of these two groups of afferents is controlled by separate sets of GABAergic interneurones synapsing directly with the intraspinal terminals of the afferent fibres. This unique arrangement allows for selective control of the information on muscle length or muscle tension, despite the convergence of muscle spindle and tendon organ afferents on second-order interneurones.

  11. Pial arteries respond earlier than penetrating arterioles to neural activation in the somatosensory cortex in awake mice exposed to chronic hypoxia: an additional mechanism to proximal integration signaling?

    PubMed

    Sekiguchi, Yuta; Takuwa, Hiroyuki; Kawaguchi, Hiroshi; Kikuchi, Takahiro; Okada, Eiji; Kanno, Iwao; Ito, Hiroshi; Tomita, Yutaka; Itoh, Yoshiaki; Suzuki, Norihiro; Sudo, Ryo; Tanishita, Kazuo; Masamoto, Kazuto

    2014-11-01

    The pial and penetrating arteries have a crucial role in regulating cerebral blood flow (CBF) to meet neural demand in the cortex. Here, we examined the longitudinal effects of chronic hypoxia on the arterial diameter responses to single whisker stimulation in the awake mouse cortex, where activity-induced responses of CBF were gradually attenuated. The vasodilation responses to whisker stimulation under prehypoxia normal conditions were 8.1% and 12% relative to their baselines in the pial arteries and penetrating arterioles, respectively. After 3 weeks of hypoxia, however, these responses were significantly reduced to 5.5% and 4.1%, respectively. The CBF response, measured using laser-Doppler flowmetry (LDF), induced by the same whisker stimulation was also attenuated (14% to 2.6%). A close linear correlation was found for the responses between the penetrating arteriolar diameter and LDF, and their temporal dynamics. After 3 weeks of chronic hypoxia, the initiation of vasodilation in the penetrating arterioles was significantly extended, but the pial artery responses remained unchanged. These results show that vasodilation of the penetrating arterioles followed the pial artery responses, which are not explainable in terms of proximal integration signaling. The findings therefore indicate an additional mechanism for triggering pial artery dilation in the neurovascular coupling.

  12. Functional capacities of tactile afferent fibres in neonatal kittens

    PubMed Central

    Ferrington, D. G.; Rowe, Mark J.

    1980-01-01

    1. Responses were recorded from individual tactile afferent fibres isolated by microdissection from the median nerve of pentobarbitone-anaesthetized neonatal kittens (1-5 days post-natal age). Experiments were also conducted on adult cats to permit precise comparisons between neonatal and adult fibres. 2. Neonatal fibres with receptive fields on the glabrous skin of the foot pads were classified into two broad groups, a slowly adapting class (40%) which responded throughout a 1 sec period of steady indentation and a rapidly adapting or dynamically sensitive class comprising 60% of units. Fibres in these two groups had overlapping conduction velocities in the range 4·3 to 7·5 m/sec and were believed to be the developing Group II afferents of the adult. 3. Neonatal slowly adapting fibres qualitatively resembled their adult counter-parts. They displayed graded stimulus-response relations which, over the steepest segment of the curves, had mean slopes of 15·7 impulses/100 μm of indentation. Plateau levels of response were often reached at amplitudes of skin indentation of < 0·5-0·7 mm. 4. Dynamically sensitive fibres with receptive fields on the glabrous skin were studied using sinusoidal cutaneous vibration which in the adult enables them to be divided into two distinct classes. However, in the neonate, they formed a continuum whether criteria of sensitivity or responsiveness were used. 5. In response to vibration neonatal fibres differed from adult ones according to the following quantitative indices: (i) sensitivity as measured by both absolute thresholds and thresholds for a 1: 1 pattern of response, both of which were higher in the neonate than in the adult at all frequencies > 50 Hz and differed by an order of magnitude at frequencies ≥ 200 Hz; (ii) responsiveness based on the mean impulse rate evoked at a fixed amplitude of cutaneous vibration; (iii) band width of vibratory sensitivity which in the neonate was confined to approximately 5-300 Hz whereas

  13. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  14. Gastric vagal afferent modulation by leptin is influenced by food intake status

    PubMed Central

    Kentish, Stephen J; O'Donnell, Tracey A; Isaacs, Nicole J; Young, Richard L; Li, Hui; Harrington, Andrea M; Brierley, Stuart M; Wittert, Gary A; Blackshaw, L Ashley; Page, Amanda J

    2013-01-01

    Energy intake is strongly influenced by vagal afferent signals from the stomach, and is also modulated by leptin. Leptin may be secreted from gastric epithelial cells, so we aimed to determine the direct effect of leptin on gastric vagal afferents under different feeding conditions. Female C57BL/6 mice were fed standard laboratory diet, high-fat diet or were food restricted. The expression of leptin receptor (Lep-R) and its signal transduction molecules in vagal afferents was determined by retrograde tracing and reverse-transcription polymerase chain reaction, and the relationship between leptin-immunopositive cells and gastric vagal afferent endings determined by anterograde tracing and leptin immunohistochemistry. An in vitro preparation was used to determine the functional effects of leptin on gastric vagal afferents and the second messenger pathways involved. Leptin potentiated vagal mucosal afferent responses to tactile stimuli, and epithelial cells expressing leptin were found close to vagal mucosal endings. After fasting or diet-induced obesity, potentiation of mucosal afferents by leptin was lost and Lep-R expression reduced in the cell bodies of gastric mucosal afferents. These effects in diet-induced obese mice were accompanied by a reduction in anatomical vagal innervation of the gastric mucosa. In striking contrast, after fasting or diet-induced obesity, leptin actually inhibited responses to distension in tension receptors. The inhibitory effect on gastric tension receptors was mediated through phosphatidylinositol 3-kinase-dependent activation of large-conductance calcium-activated potassium channels. The excitatory effect of leptin on gastric mucosal vagal afferents was mediated by phospholipase C-dependent activation of canonical transient receptor potential channels. These data suggest the effect of leptin on gastric vagal afferent excitability is dynamic and related to the feeding state. Paradoxically, in obesity, leptin may reduce responses to

  15. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  16. Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles

    PubMed Central

    Ikeda, Ryo

    2016-01-01

    Whisker hair follicles are sensory organs that sense touch and perform tactile discrimination in animals, and they are sites where sensory impulses are initiated when whisker hairs touch an object. The sensory signals are then conveyed by whisker afferent fibers to the brain for sensory perception. Electrophysiological property and chemical sensitivity of whisker afferent fibers, important factors affecting whisker sensory processing, are largely not known. In the present study, we performed patch-clamp recordings from pre-identified whisker afferent neurons in whole-mount trigeminal ganglion preparations and characterized their electrophysiological property and sensitivity to ATP, serotonin and glutamate. Of 97 whisker afferent neurons examined, 67% of them are found to be large-sized (diameter ≥45 µm) cells and 33% of them are medium- to small-sized (diameter <45 µm) cells. Almost every large-sized whisker afferent neuron fires a single action potential but many (40%) small/medium-sized whisker afferent neurons fire multiple action potentials in response to prolonged stepwise depolarization. Other electrophysiological properties including resting membrane potential, action potential threshold, and membrane input resistance are also significantly different between large-sized and small/medium-sized whisker afferent neurons. Most large-sized and many small/medium-sized whisker afferent neurons are sensitive to ATP and/or serotonin, and ATP and/or serotonin could evoke strong inward currents in these cells. In contrast, few whisker afferent neurons are sensitive to glutamate. Our results raise a possibility that ATP and/or serotonin may be chemical messengers involving sensory signaling for different types of rat whisker afferent fibers. PMID:27927797

  17. Melittin selectively activates capsaicin-sensitive primary afferent fibers.

    PubMed

    Shin, Hong Kee; Kim, Jin Hyuk

    2004-08-06

    Whole bee venom (WBV)-induced pain model has been reported to be very useful for the study of pain. However, the major constituent responsible for the production of pain by WBV is not apparent. Intraplantar injection of WBV and melittin dramatically reduced mechanical threshold, and increased flinchings and paw thickness. In behavioral experiments, capsaicin pretreatment almost completely prevented WBV- and melittin-induced reduction of mechanical threshold and flinchings. Intraplantar injection of melittin increased discharge rate of dorsal horn neurons only with C fiber input from peripheral receptive field, which was completely blocked by topical application of capsaicin to sciatic nerve. These results suggest that both melittin and WBV induce nociceptive responses by selective activation of capsaicin-sensitive afferent fibers.

  18. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    PubMed Central

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  19. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents.

    PubMed

    Wild, Vanessa; Messlinger, Karl; Fischer, Michael J M

    2015-08-18

    Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation.

  20. Cardiac afferent activity modulates the expression of racial stereotypes

    PubMed Central

    Azevedo, Ruben T.; Garfinkel, Sarah N.; Critchley, Hugo D.; Tsakiris, Manos

    2017-01-01

    Negative racial stereotypes tend to associate Black people with threat. This often leads to the misidentification of harmless objects as weapons held by a Black individual. Yet, little is known about how bodily states impact the expression of racial stereotyping. By tapping into the phasic activation of arterial baroreceptors, known to be associated with changes in the neural processing of fearful stimuli, we show activation of race-threat stereotypes synchronized with the cardiovascular cycle. Across two established tasks, stimuli depicting Black or White individuals were presented to coincide with either the cardiac systole or diastole. Results show increased race-driven misidentification of weapons during systole, when baroreceptor afferent firing is maximal, relative to diastole. Importantly, a third study examining the positive Black-athletic stereotypical association fails to demonstrate similar modulations by cardiac cycle. We identify a body–brain interaction wherein interoceptive cues can modulate threat appraisal and racially biased behaviour in context-dependent ways. PMID:28094772

  1. Selective cortical and segmental control of primary afferent depolarization of single muscle afferents in the cat spinal cord.

    PubMed

    Eguibar, J R; Quevedo, J; Rudomin, P

    1997-03-01

    This study was primarily aimed at investigating the selectivity of the cortico-spinal actions exerted on the pathways mediating primary afferent depolarization (PAD) of muscle spindle and tendon organ afferents ending within the intermediate nucleus at the L6-L7 segmental level. To this end we analyzed, in the anesthetized cat, the effects produced by electrical stimulation of sensory nerves and of the cerebral cortex on (a) the intraspinal threshold of pairs of single group I afferent fibers belonging to the same or to different hindlimb muscles and (b) the intraspinal threshold of two collaterals of the same muscle afferent fiber. Afferent fibers were classified in three categories, according to the effects produced by stimulation of segmental nerves and of the cerebral cortex. Twenty-five of 40 fibers (62.5%) were depolarized by stimulation of group I posterior biceps and semitendinosus (PBSt) or tibialis (Tib) fibers, but not by stimulation of the cerebral cortex or of cutaneous and joint nerves, which instead inhibited the PBSt- or Tib-induced PAD (type A PAD pattern, usually seen in Ia fibers). The remaining 15 fibers (37.5%) were all depolarized by stimulation of the PBSt or Tib nerves and the cerebral cortex. Stimulation of cutaneous and joint nerves produced PAD in 10 of those 15 fibers (type B PAD pattern) and inhibited the PBSt- or Tib-induced PAD in the 5 remaining fibers (type C PAD pattern). Fibers with a type B or C PAD pattern are likely to be Ib. Not all sites in the cerebral cortex inhibited with the same effectiveness the segmentally induced PAD of group I fibers with a type A PAD pattern. With the weakest stimulation of the cortical surface, the most effective sites that inhibited the PAD of individual fibers were surrounded by less effective sites, scattered all along the motor cortex (area 4gamma and 6) and sensory cortex (areas 3, 2 and 1), far beyond the area of projection of group I fibers from the hindlimb. With higher strengths of

  2. K+ Currents in Isolated Vestibular Afferent Calyx Terminals

    PubMed Central

    Dhawan, Ritu; Mann, Scott E.; Meredith, Frances L.

    2010-01-01

    Vestibular hair cells transduce mechanical displacements of their hair bundles into an electrical receptor potential which modulates transmitter release and subsequent action potential firing in afferent neurons. To probe ionic mechanisms underlying sensory coding in vestibular calyces, we used the whole-cell patch-clamp technique to record action potentials and K+ currents from afferent calyx terminals isolated from the semicircular canals of Mongolian gerbils. Calyx terminals showed minimal current at the mean zero-current potential (−60 mV), but two types of outward K+ currents were identified at potentials above −50 mV. The first current was a rapidly activating and inactivating K+ current that was blocked by 4-aminopyridine (4-AP, 2.5 mM) and BDS-I (up to 250 nM). The time constant for activation of this current decreased with membrane depolarization to a minimum value of ∼1 ms. The 4-AP-sensitive current showed steady-state inactivation with a half-inactivation of approximately −70 mV. A second, more slowly activating current (activation time constant was 8.5 ± 0.7 ms at −8 mV) was sensitive to TEA (30 mM). The TEA-sensitive current also showed steady-state inactivation with a half-inactivation of −95.4 ± 1.4 mV, following 500-ms duration conditioning pulses. A combination of 4-AP and TEA blocked ∼90% of the total outward current. In current clamp, single Na+-dependent action potentials were evoked following hyperpolarization to potentials more negative than the resting potential. 4-AP application increased action potential width, whereas TEA both increased the width and greatly reduced repolarization of the action potential. PMID:20407915

  3. Vagal afferent control of opioidergic effects in rat brainstem circuits

    PubMed Central

    Browning, Kirsteen N; Zheng, Zhongling; Gettys, Thomas W; Travagli, R Alberto

    2006-01-01

    We demonstrated recently that increasing the levels of cAMP allows opioids to modulate GABAergic synaptic transmission between the nucleus of the tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMV). Using a combination of electrophysiological, immunohistochemical and biochemical approaches, we provide evidence that vagal afferent fibres dampen cAMP levels within the vagal brainstem circuits via tonic activation of group II metabotropic glutamate receptors (mGluRs). Whole-cell patch-clamp recordings were made from identified neurons of the rat DMV. Following chronic vagal deafferentation, the opioid agonist methionine-enkephalin (ME) inhibited the amplitude of evoked IPSC (eIPSC) in 32 of 33 neurons, without exogenous enhancement of cAMP levels. The ME-induced inhibition was prevented by the group II mGluR-selective agonist APDC. Following perfusion with the group II mGluR-selective antagonist EGLU, ME inhibited eIPSC amplitude in brainstem slices of control rats. Immunohistochemical experiments revealed that, following vagal deafferentation, μ-opioid receptors were colocalized on GABAergic profiles apposing DMV neurons; the number of colocalized profiles was significantly decreased by pretreatment with APDC. Radioimmunoassay and Western blot analysis showed that cAMP and phosphorylated cyclic AMP response element binding protein (pCREB) levels in the dorsal vagal complex were increased following vagal deafferentation. Our data show that by tonically dampening the levels of cAMP within the GABAergic synaptic contacts, activated group II mGluRs prevent the modulation of this synapse by endogenous opioids. These data suggest that the plasticity, hence the response, of central circuits controlling the vagal motor outflow to visceral organs is modulated and finely tuned by vagal afferent fibres. PMID:16825311

  4. Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity.

    PubMed

    Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung; Tavares, Matthew J; Gokina, Natalia; Brayden, Joseph E

    2014-07-01

    Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs (P < 0.01), and VSM calcium was 200 ± 20 nmol/l in PAs vs. 104 ± 15 nmol/l in MCAs (P < 0.01). In vessels permeabilized with Staphylococcus aureus α-toxin, PAs were not more sensitive to calcium, suggesting calcium sensitization was not at the level of the contractile apparatus. PAs were 30-fold more sensitive to the voltage-dependent calcium channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs;P < 0.01); however, electrophysiological properties of the VDCC were not different in VSM. PAs had little to no response to the calcium-activated potassium channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

  5. Neutralizing VEGF Decreases Tortuosity and Alters Endothelial Cell Division Orientation in Arterioles and Veins in a Rat Model of ROP

    PubMed Central

    Hartnett, M. Elizabeth; Martiniuk, David; Byfield, Grace; Geisen, Pete; Zeng, Gefei; Bautch, Victoria L.

    2008-01-01

    Purpose To study the effects of vascular endothelial growth factor (VEGF) on endothelial nitric oxide synthetase (eNOS) and retinal vascular tortuosity and cleavage planes in a rat model of retinopathy of prematurity (ROP). Methods Within 4 hours of birth, pups and mothers were cycled between 50% and 10% oxygen daily. At postnatal day (p)12, pups received either intravitreous anti-rat neutralizing antibody to VEGF or control nonimmune rat IgG in one eye and returned to oxygen cycling until p14 when they were placed in room air (RA) for 4 days (50/10 oxygen-induced retinopathy [50/10 OIR]). Tortuosity indices and endothelial cleavage plane angles relative to the long axes of the major retinal vessels during anaphase were calculated from phosphohistone- and Alexa-isolectin-stained retinal flatmounts. Some retinas were processed for eNOS protein or phosphorylated/total eNOS. Results Retinas from 50/10 OIR had increased tortuosity over time with peaks at p12 and p14 (P < 0.001 vs. RA) before the development of intravitreous neovascularization, which peaked at p18. Compared with RA, eNOS/actin in 50/10 OIR retinas was increased at p12 (P = 0.0003) and p14 (P = 0.047). Inhibition of VEGF with a neutralizing antibody decreased tortuosity and caused endothelial mitosis cleavage planes to orient in favor of vessel elongation but did not affect eNOS protein or activation. Conclusions In the 50/10 OIR model, a model with relevance to ROP, arteriolar tortuosity, and venous dilation are increased through VEGF, which influences the orientation of endothelial cell cleavage in major arterioles and veins, independent of eNOS. PMID:18378573

  6. Treatment for cerebral small vessel disease: effect of relaxin on the function and structure of cerebral parenchymal arterioles during hypertension.

    PubMed

    Chan, Siu-Lung; Sweet, Julie G; Cipolla, Marilyn J

    2013-10-01

    We investigated the effect of hypertension on the function and structure of cerebral parenchymal arterioles (PAs), a major target of cerebral small vessel disease (SVD), and determined whether relaxin is a treatment for SVD during hypertension. PAs were isolated from 18-wk-old female normotensive Wistar-Kyoto (WKY) rats, spontaneous hypertensive rats (SHRs), and SHRs treated with human relaxin 2 for 14 d (4 μg/h; n=8/group) and studied using a pressurized arteriograph system. Hypertension reduced PA inner diameter (58±3 vs. 49±3 μm at 60 mmHg in WKY rats, P<0.05), suggesting inward remodeling that was reversed by relaxin (56±4 μm, P<0.05). Relaxin also increased PA distensibility in SHRs (34±2 vs. 10±2% in SHRs, P<0.05). Relaxin was detected in cerebrospinal fluid (110±30 pg/ml) after systemic administration, suggesting that it crosses the blood-brain barrier (BBB). Relaxin receptors (RXFP1/2) were not detected in cerebral vasculature, but relaxin increased vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2) expression in brain cortex. Inhibition of VEGF receptor tyrosine kinase (axitinib, 4 mg/kg/d, 14 d) had no effect on increased distensibility with relaxin, but caused outward hypertrophic remodeling of PAs from SHRs. These results suggest that relaxin crosses the BBB and activates MMP-2 in brain cortex, which may interact with PAs to increase distensibility. VEGF appears to be involved in remodeling of PAs, but not relaxin-induced increased distensibility.

  7. Contractile 5-HT1 receptors in human isolated pial arterioles: correlation with 5-HT1D binding sites.

    PubMed Central

    Hamel, E.; Bouchard, D.

    1991-01-01

    1. The 5-hydroxytryptamine (5-HT) receptor responsible for inducing vasoconstriction in human isolated pial arterioles has been pharmacologically characterized. 2. Of several 5-HT agonists tested, 5-carboxamidotryptamine (5-CT) was the most potent and the rank order of agonist potency can be summarized as: 5-CT greater than 5-HT greater than RU 24969 = alpha-methyl-5-HT = methysergide much greater than MDL 72832 = 2-methyl-5-HT much greater than 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT). With few exceptions, the maximal contractile responses of these agonists were comparable to that induced by 5-HT. 3. A correlation analysis performed between the agonists vascular potency (pD2 values) and their affinities (pKD values) published at various subtypes of 5-HT binding sites showed a positive significant correlation with rat cortical 5-HT1B (r = 0.86; P less than 0.01) and human caudate 5-HT1D (r = 0.98; P less than 0.005) subtypes. 4. Selective antagonists at 5-HT2 (ketanserin, mianserin, MDL 11939) and 5-HT3 (MDL 72222) sites were totally devoid of inhibitory activity on the 5-HT-induced contraction, an observation which agreed with the agonist data and further excluded activation of these receptors. In contrast, the 5-HT1-like/5-HT2 antagonist methiothepin and the non-selective 5-HT1D compound metergoline inhibited with high affinity the contraction induced by 5-HT with respective pA2 values of 8.55 +/- 0.16 and 6.88 +/- 0.05. This contractile response was, however, insensitive to 5-HT1B (propranolol) and 5-HT1C (mesulergine, mianserin) antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043924

  8. Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat

    PubMed Central

    Hermes, Sam M.; Andresen, Michael C.; Aicher, Sue A.

    2016-01-01

    The vagus nerve is dominated by afferent fibers that convey sensory information from the viscera to the brain. Most vagal afferents are unmyelinated, slow-conducting C-fibers, while a smaller portion are myelinated, fast-conducting A-fibers. Vagal afferents terminate in the nucleus tractus solitarius (NTS) in the dorsal brainstem and regulate autonomic and respiratory reflexes, as well as ascending pathways throughout the brain. Vagal afferents form glutamatergic excitatory synapses with postsynaptic NTS neurons that are modulated by a variety of channels. The organization of vagal afferents with regard to fiber type and channels is not well understood. In the present study, we used tract tracing methods to identify distinct populations of vagal afferents to determine if key channels are selectively localized to specific groups of afferent fibers. Vagal afferents were labeled with isolectin B4 (IB4) or cholera toxin B (CTb) to detect unmyelinated and myelinated afferents, respectively. We find that TRPV1 channels are preferentially found in unmyelinated vagal afferents identified with IB4, with almost half of all IB4 fibers showing co-localization with TRPV1. These results agree with prior electrophysiological findings. In contrast, we found that the ATP-sensitive channel P2X3 is found in a subset of both myelinated and unmyelinated vagal afferent fibers. Specifically, 18% of IB4 and 23% of CTb afferents contained P2X3. The majority of CTb-ir vagal afferents contained neither channel. Since neither channel was found in all vagal afferents, there are likely further degrees of heterogeneity in the modulation of vagal afferent sensory input to the NTS beyond fiber type. PMID:26706222

  9. Novel Afferent Terminal Structure in the Crista Ampullaris of the Goldfish, Carassius auratus

    NASA Technical Reports Server (NTRS)

    Lanford, Pamela J.; Popper, Arthur N.

    1996-01-01

    Using transmission electron microscopy, we have identified a new type of afferent terminal structure in the crista ampullaris of the goldfish Carassius auratus. In addition to the bouton-type afferent terminals previously described in the ear of this species, the crista also contained enlarged afferent terminals that enveloped a portion of the basolateral hair cell membrane. The hair cell membrane was evaginated and protruded into the afferent terminal in a glove-and-finger configuration. The membranes of the two cells were regularly aligned in the protruded region of the contact and had a distinct symmetrical electron density. The electron-dense profiles of these contacts were easily identified and were present in every crista sampled. In some cases, efferent terminals synapsed onto the afferents at a point where the hair cell protruded into the terminal. The ultrastructural similarities of the goldfish crista afferents to calyx afferents found in amniotes (birds, reptiles, and mammals) are discussed. The results of the study support the hypothesis that structural variation in the vertebrate inner ear may have evolved much earlier in evolution than previously supposed.

  10. The effects of antidromic discharges on orthodromic firing of primary afferents in the cat.

    PubMed

    Gossard, J P; Bouyer, L; Rossignol, S

    1999-04-17

    This study investigated the effects of antidromically conducted nerve impulses on the transmission of orthodromic volleys in primary afferents of the hindlimb in decerebrated paralyzed cats. Two protocols were used: (A) Single skin and muscle afferents (N=20) isolated from the distal part of cut dorsal rootlets (L7-S1) were recorded while stimulation was applied more caudally. The results showed that during the trains of three to 20 stimuli, the orthodromic firing frequency decreased or ceased, depending on the frequency of stimulation. Remarkably, subsequent to these trains, the occurrence of orthodromic spikes could be delayed for hundreds of ms (15/20 afferents) and sometimes stopped for several seconds (10/20 afferents). Longer stimulation trains, simulating antidromic bursts reported during locomotion, caused a progressive decrease, and a slow recovery of, orthodromic firing frequency (7/20 afferents), indicating a cumulative long-lasting depressing effect from successive bursts. (B) Identified stretch-sensitive muscle afferents were recorded intra-axonally and antidromic spikes were evoked by the injection of square pulses of current through the micropipette. In this case, one to three antidromic spikes were sufficient to delay the occurrence of the next orthodromic spike by more than one control inter-spike interval. If the control inter-spike interval was decreased by stretching the muscle, the delay evoked by antidromic spikes decreased proportionally. Overall, these findings suggest that antidromic activity could alter the mechanisms underlying spike generation in peripheral sensory receptors and modify the orthodromic discharges of afferents during locomotion.

  11. Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis.

    PubMed

    Garretson, John T; Szymanski, Laura A; Schwartz, Gary J; Xue, Bingzhong; Ryu, Vitaly; Bartness, Timothy J

    2016-08-01

    Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). 2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis.

  12. Hair cell tufts and afferent innervation of the bullfrog crista ampullaris

    NASA Technical Reports Server (NTRS)

    Myers, Steven F.; Lewis, Edwin R.

    1990-01-01

    Within the bullfrog semicircular canal crista, hair cell tuft types were defined and mapped with the aid of scanning electron microscopy. Dye-filled planar afferent axons had mean distal axonal diameters of 1.6-4.9 microns, highly branched arbors, and contacted 11-24 hair cells. Dye-filled isthmus afferent axons had mean distal axonal diameters of 1.8-7.9 microns, with either small or large field arbors contacting 4-9 or 25-31 hair cells. The estimated mean number of contacts per innervated hair cell was 2.2 for planar and 1.3 for isthmus afferent neurons. Data on evoked afferent responses were available only for isthmus units that were observed to respond to our microrotational stimuli. Of 21 such afferent neurons, eight were successfully dye-filled. Within this sample, high-gain units had large field arbors and lower-gain units had small field arbors. The sensitivity of each afferent neuron was analyzed in terms of noise equivalent input (NEI), the stimulus amplitude for which the afferent response amplitude is just equivalent to the rms deviation of the instantaneous spike rate. NEI for isthmus units varied from 0.63 to 8.2 deg/s; the mean was 3.2 deg/s.

  13. Technetium-99m HIDA hepatobiliary scanning in evaluation of afferent loop syndrome

    SciTech Connect

    Sivelli, R.; Farinon, A.M.; Sianesi, M.; Percudani, M.; Ugolotti, G.; Calbiani, B.

    1984-08-01

    A study of 118 patients, operated on with Billroth II gastrectomy for peptic disease and affected by postgastrectomy syndromes, was carried out. Fifty patients were investigated by means of technetium-99m HIDA hepatobiliary scanning. In 18 patients, in whom an afferent loop syndrome was clinically suspected, hepatobiliary scanning demonstrated an altered afferent loop emptying in 8 and atonic distension of the gallbladder without afferent loop motility changes in 10. Among the patients in the first group, four were treated with a biliary diversion surgical procedure and in the second group, two patients underwent cholecystectomy. Our findings indicate that biliary vomiting, right upper abdominal pain pyrosis, and biliary diarrhea in Billroth II gastrectomized patients are not always pathognomonic symptoms of afferent loop syndrome. Technetium-99m HIDA hepatobiliary scanning represents the only diagnostic means of afferent loop syndrome definition. A differential diagnosis of abnormal afferent loop emptying and gallbladder dyskinesia is necessary for the management planning of these patients, and furthermore, when a surgical treatment is required, biliary diversion with Roux-Y anastomosis or Braun's biliary diversion seems the treatment of choice for afferent loop syndrome, whereas cholecystectomy represents the best procedure for atonic distension of the gallbladder.

  14. Vagal afferents sense meal-associated gastrointestinal and pancreatic hormones: mechanism and physiological role.

    PubMed

    Iwasaki, Yusaku; Yada, Toshihiko

    2012-12-01

    Some gastrointestinal and pancreatic hormones are potently secreted by meal intake and reduce food intake, therefore these hormones play a role in the meal-evoked satiety peptides. Previous reports have demonstrated that peripheral administration of these gastrointestinal or pancreatic hormones decrease feeding and the anorectic effects are abolished by lesions of vagal afferent nerves using surgical or chemical protocols, indicative of the involvement of the vagal afferents. Vagal afferent nerves link between several peripheral organs and the nucleus tractus solitarius of the brainstem. The present review focuses on cholecystokinin, peptide YY(3-36), pancreatic polypeptide, and nesfatin-1 released from endocrine cells of the gut and pancreas. These hormonal peptides directly act on and increase cytosolic Ca(2+) in vagal afferent nodose ganglion neurons and finally suppress food intake via vagal afferents. Therefore, peripheral terminals of vagal afferents could sense gastrointestinal and pancreatic hormones and regulate food intake. Here, we review how the vagal afferent neurons sense a variety of gastrointestinal and pancreatic hormones and discuss its physiological significance in regulation of feeding.

  15. Local control of information flow in segmental and ascending collaterals of single afferents.

    PubMed

    Lomelí, J; Quevedo, J; Linares, P; Rudomin, P

    1998-10-08

    In the vertebrate spinal cord, the activation of GABA(gamma-amino-butyric acid)-releasing interneurons that synapse with intraspinal terminals of sensory fibres leading into the central nervous system (afferent fibres) produces primary afferent depolarization and presynaptic inhibition. It is not known to what extent these presynaptic mechanisms allow a selective control of information transmitted through specific sets of intraspinal branches of individual afferents. Here we study the local nature of the presynaptic control by measuring primary afferent depolarization simultaneously in two intraspinal collaterals of the same muscle spindle afferent. One of these collaterals ends at the L6-L7 segmental level in the intermediate nucleus, and the other ascends to segment L3 within Clarke's column, the site of origin of spinocerebellar neurons. Our results indicate that there are central mechanisms that are able to affect independently the synaptic effectiveness of segmental and ascending collaterals of individual muscle spindle afferents. Focal control of presynaptic inhibition thus allows the intraspinal branches of afferent fibres to function as a dynamic assembly that can be fractionated to convey information to selected neuronal targets. This may be a mechanism by which different spinal postsynaptic targets that are coupled by sensory input from a common source could be uncoupled.

  16. Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons

    PubMed Central

    Peters, James H.; McDougall, Stuart J.; Fawley, Jessica A.; Smith, Stephen M.; Andresen, Michael C.

    2010-01-01

    SUMMARY TRPV1 receptors feature prominently in nociception of spinal primary afferents but are also expressed in unmyelinated cranial visceral primary afferents linked to homeostatic regulation. Cranial visceral afferents enter the brain at the solitary tract nucleus (NTS) to control the heart, lungs and other vital organs. Here we identify a novel role for central TRPV1 in the activity-dependent facilitation of glutamatergic transmission from solitary tract (ST) afferents. Fast, synchronous ST-NTS transmission from capsaicin sensitive (TRPV1+) and insensitive (TRPV1−) afferents was similar. However, afferent activation triggered long lasting asynchronous glutamate release only from TRPV1+ synapses. Asynchronous release was proportional to synchronous EPSC amplitude, activity, and calcium entry. TRPV1 antagonists and low temperature blocked asynchronous release but not evoked EPSCs. At physiological afferent frequencies, asynchronous release strongly potentiated the duration of postsynaptic spiking. This activity dependent TPRV1-mediated facilitation is a novel form of synaptic plasticity that brings a unique central integrative feature to the CNS and autonomic regulation. PMID:20223201

  17. Age-Related Changes in Vagal Afferents Innervating the Gastrointestinal Tract

    PubMed Central

    Phillips, Robert J.; Walter, Gary C.; Powley, Terry L.

    2009-01-01

    Recent progress in understanding visceral afferents, some of it reviewed in the present issue, serves to underscore how little is known about the aging of the visceral afferents in the gastrointestinal (GI) tract. In spite of the clinical importance of the issue--with age, GI function often becomes severely compromised--only a few initial observations on age-related structural changes of visceral afferents are available. Primary afferent cell bodies in both the nodose ganglia and dorsal root ganglia lose Nissl material and accumulate lipofucsin, inclusions, aggregates, and tangles. Additionally, in changes that we focus on in the present review, vagal visceral afferent terminals in both the muscle wall and the mucosa of the GI tract exhibit age-related structural changes. In aged animals, both of the vagal terminal types examined, namely intraganglionic laminar endings and villus afferents, exhibit dystrophic or regressive morphological changes. These neuropathies are associated with age-related changes in the structural integrity of the target organs of the affected afferents, suggesting that local changes in trophic environment may give rise to the aging of GI innervation. Given the clinical relevance of GI tract aging, a more complete understanding both of how aging alters the innervation of the gut and of how such changes might be mitigated should be made research priorities. PMID:19665435

  18. Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice

    PubMed Central

    Brierley, Stuart M; Carter, R; Jones, W; Xu, Linjing; Robinson, David R; Hicks, Gareth A; Gebhart, GF; Blackshaw, L Ashley

    2005-01-01

    Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here we determined whether these pathways also differ in their chemosensitivity and receptor expression. Using an in vitro mouse colon preparation, individual primary afferents were tested with selective P2X and transient receptor potential vanilloid receptor 1 (TRPV1) receptor ligands. Afferent cell bodies in thoracolumbar and lumbosacral dorsal root ganglia (DRG) were retrogradely labelled from the colon and analysed for P2X3- and TRPV1-like immunoreactivity (LI). Forty per cent of LSN afferents responded to α,β-methylene adenosine 5′-triphosphate (α,β-meATP; 1 mm), an effect that was concentration dependent and reversed by the P2X antagonist pyridoxyl5-phosphate 6-azophenyl-2′,4′-disulphonic acid (PPADS) (100 μm). Significantly fewer PN afferents (7%) responded to α,β-meATP. Correspondingly, 36% of colonic thoracolumbar DRG neurones exhibited P2X3-LI compared with only 19% of colonic lumbosacral neurones. Capsaicin (3 μm) excited 61% of LSN afferents and 47% of PN afferents; 82% of thoracolumbar and 50% of lumbosacral colonic DRG neurones displayed TRPV1-LI. Mechanically insensitive afferents were recruited by α,β-meATP or capsaicin, and were almost exclusive to the LSN. Capsaicin-responsive LSN afferents displayed marked mechanical desensitization after responding to capsaicin, which did not occur in capsaicin-responsive PN afferents. Therefore, colonic LSN and PN pathways differ in their chemosensitivity to known noxious stimuli and their corresponding receptor expression. As these pathways relay information that may relate to symptoms in functional gastrointestinal disease, these results may have implications for the efficacy of therapies targeting receptor modulation. PMID:15946967

  19. A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin

    PubMed Central

    Foss, Jason D.; Wainford, Richard D.; Engeland, William C.; Fink, Gregory D.

    2014-01-01

    Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt other afferent pathways. To do this, we adapted a technique for sensory denervation of the adrenal gland by topical application of capsaicin and tested the hypothesis that exposure of the renal nerves to capsaicin (renal-CAP) causes ablation of afferent but not efferent renal nerves. Renal-CAP had no effect on renal content of the efferent nerve markers tyrosine hydroxylase and norepinephrine; however, the afferent nerve marker, calcitonin gene-related peptide was largely depleted from the kidney 10 days after intervention, but returned to roughly half of control levels by 7 wk postintervention. Moreover, renal-CAP abolished the cardiovascular responses to acute pharmacological stimulation of afferent renal nerves. Renal-CAP rats showed normal weight gain, as well as cardiovascular and fluid balance regulation during dietary sodium loading. To some extent, renal-CAP did blunt the bradycardic response and increase the dipsogenic response to increased salt intake. Lastly, renal-CAP significantly attenuated the development of deoxycorticosterone acetate-salt hypertension. These results demonstrate that renal-CAP effectively causes selective ablation of afferent renal nerves in rats. PMID:25411365

  20. Estradiol alters the chemosensitive cardiac afferent reflex in female rats by augmenting sympathoinhibition and attenuating sympathoexcitation.

    PubMed

    Pinkham, Maximilian I; Barrett, Carolyn J

    2015-06-01

    The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were performed in anaesthetized, sinoaortic baroreceptor denervated male, female and ovariectomized female (OVX) Wistar rats with either intact cardiac innervation or bilateral vagotomy. To investigate the chemosensitive cardiac afferent reflexes renal SNA, heart rate (HR) and arterial pressure (AP) were recorded before and following application of capsaicin onto the epicardial surface of the left ventricle. Compared to males, ovary-intact females displayed similar cardiac afferent reflex mediated changes in renal SNA albeit with a reduced maximum sympathetic reflex driven increase in renal SNA. In females, ovariectomy significantly attenuated the cardiac vagal afferent reflex mediated inhibition of renal SNA (renal SNA decreased 2 ± 17% in OVX versus -50 ± 4% in ovary-intact females, P < 0.05) and augmented cardiac sympathetic afferent reflex mediated sympathoexcitation (renal SNA increased 91 ± 11% in OVX vs 62 ± 9% in ovary-intact females, P < 0.05) so that overall increases in reflex driven sympathoexcitation were significantly enhanced. Chronic estradiol replacement, but not progesterone replacement, begun at time of ovariectomy restored cardiac afferent reflex responses to be similar as ovary-intact females. Vagal denervation eliminated all group differences. The current findings show ovariectomy in female rats, mimicking menopause in women, results in greater chemosensitive cardiac afferent reflex driven sympathoexcitation and does so, at least partly, via the loss of estradiols actions on the cardiac vagal afferent reflex pathway. © 2015 Wiley Publishing Asia Pty Ltd.

  1. A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin.

    PubMed

    Foss, Jason D; Wainford, Richard D; Engeland, William C; Fink, Gregory D; Osborn, John W

    2015-01-15

    Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due to ablation of afferent or efferent renal nerves. To investigate the role of afferent renal nerves in arterial pressure regulation, previous studies have used methods that disrupt both renal and nonrenal afferent signaling. The present study was conducted to develop and validate a technique for selective ablation of afferent renal nerves that does not disrupt other afferent pathways. To do this, we adapted a technique for sensory denervation of the adrenal gland by topical application of capsaicin and tested the hypothesis that exposure of the renal nerves to capsaicin (renal-CAP) causes ablation of afferent but not efferent renal nerves. Renal-CAP had no effect on renal content of the efferent nerve markers tyrosine hydroxylase and norepinephrine; however, the afferent nerve marker, calcitonin gene-related peptide was largely depleted from the kidney 10 days after intervention, but returned to roughly half of control levels by 7 wk postintervention. Moreover, renal-CAP abolished the cardiovascular responses to acute pharmacological stimulation of afferent renal nerves. Renal-CAP rats showed normal weight gain, as well as cardiovascular and fluid balance regulation during dietary sodium loading. To some extent, renal-CAP did blunt the bradycardic response and increase the dipsogenic response to increased salt intake. Lastly, renal-CAP significantly attenuated the development of deoxycorticosterone acetate-salt hypertension. These results demonstrate that renal-CAP effectively causes selective ablation of afferent renal nerves in rats.

  2. Functional Organization of Cutaneous and Muscle Afferent Synapses onto Immature Spinal Lamina I Projection Neurons

    PubMed Central

    Li, Jie

    2017-01-01

    It is well established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared with skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared with pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn neurons process sensory input from muscle versus skin at the synaptic level. Using a novel ex vivo spinal cord preparation, here we identify the functional organization of muscle and cutaneous afferent synapses onto immature rat lamina I spino-parabrachial neurons, which serve as a major source of nociceptive transmission to the brain. Stimulation of the gastrocnemius nerve and sural nerve revealed significant convergence of muscle and cutaneous afferent synaptic input onto individual projection neurons. Muscle afferents displayed a higher probability of glutamate release, although short-term synaptic plasticity was similar between the groups. Importantly, muscle afferent synapses exhibited greater relative expression of Ca2+-permeable AMPARs compared with cutaneous inputs. In addition, the prevalence and magnitude of spike timing-dependent long-term potentiation were significantly higher at muscle afferent synapses, where it required Ca2+-permeable AMPAR activation. Collectively, these results provide the first evidence for afferent-specific properties of glutamatergic transmission within the superficial dorsal horn. A larger propensity for activity-dependent strengthening at muscle afferent synapses onto developing spinal projection neurons could contribute to the enhanced ability of these sensory inputs to sensitize central nociceptive networks and thereby evoke persistent pain in children following injury. SIGNIFICANCE STATEMENT The neurobiological mechanisms underlying the high prevalence of chronic

  3. Selective cortical control of information flow through different intraspinal collaterals of the same muscle afferent fiber.

    PubMed

    Eguibar, J R; Quevedo, J; Jiménez, I; Rudomin, P

    1994-04-18

    We have analyzed in the anesthetized cat the effects of electrical stimulation of the cerebral cortex on the intraspinal threshold of two collaterals belonging to the same muscle spindle or tendon organ afferent fiber. The results obtained provide, for the first time, direct evidence showing that the motor cortex is able to modify, in a highly selective manner, the synaptic effectiveness of individual collaterals of the same primary afferent fiber. This presynaptic control could function as a mechanism that allows funneling of information to specific groups of spinal neurons in the presence of extensive intraspinal branching of the afferent fibers.

  4. Enterolith Causing Afferent Loop Obstruction: A Case Report and Literature Review

    SciTech Connect

    Lee, Michael C.; Bui, James T.; Knuttinen, M-Grace; Gaba, Ron C.; Scott Helton, W.; Owens, Charles A.

    2009-09-15

    Enterolith formation is a rare cause of afferent limb obstruction following Billroth II gastrectomy and Roux-en-Y hepaticojejunostomy surgery. A case of ascending cholangitis caused by an enterolith incarcerated in the afferent loop of a 15-year-old Roux-en-Y hepaticojejunostomy was emergently decompressed under direct ultrasound guidance prior to surgery. This is the thirteenth reported case of an enterolith causing afferent loop obstruction. A discussion of our management approach and a review of the relevant literature are presented.

  5. Response properties of gerbil otolith afferents to small angle pitch and roll tilts

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.; Angelaki, D. E.; Correia, M. J.

    1991-01-01

    The responses from isolated single otolith afferent fibers were obtained to small angle sinusoidal pitch and roll tilts in anesthetized gerbils. The stimulus directions that produced the maximum (response vector) and minimum response sensitivities were determined for each otolith afferent, with response vectors for the units being spread throughout the horizontal plane, similar to those reported for other species. A breadth of tuning measure was derived, with narrowly tuned neurons responding maximally to stimulation in one direction and minimally along an orthogonal ('null') direction. Most (approximately 80%) otolith afferents are narrowly tuned, however, some fibers were broadly tuned responding significantly to stimulations in any direction in the horizontal plane. The number of broadly tuned otolith afferents (approximately 20%) differs significantly from the more substantial number of broadly tuned vestibular nuclei neurons (88%) recently reported in rats.

  6. Changes in PAD patterns of group I muscle afferents after a peripheral nerve crush.

    PubMed

    Enríquez, M; Jiménez, I; Rudomin, P

    1996-01-01

    In the anesthetized cat we have analyzed the changes in primary afferent depolarization (PAD) evoked in single muscle spindle and tendon organ afferents at different times after their axons were crushed in the periphery and allowed to regenerate. Medial gastrocnemius (MG) afferents were depolarized by stimulation of group I fibers in the posterior biceps and semitendinosus nerve (PBSt), as soon as 2 weeks after crushing their axons in the periphery, in some cases before they could be activated by physiological stimulation of muscle receptors. Two to twelve weeks after crushing the MG nerve, stimulation of the PBSt produced PAD in all MG fibers reconnected with presumed muscle spindles and tendon organs. The mean amplitude of the PAD elicited in afferent fibers reconnected with muscle spindles was increased relative to values obtained from Ia fibers in intact (control) preparations, but remained essentially the same in fibers reconnected with tendon organs. Quite unexpectedly, we found that, between 2 and 12 weeks after crushing the MG nerve, stimulation of the bulbar reticular formation (RF) produced PAD in most afferent fibers reconnected with muscle spindle afferents. The mean amplitude of the PAD elicited in these fibers was significantly increased relative to the PAD elicited in muscle spindle afferents from intact preparations (from 0.08 +/- 0.4 to 0.47 +/- 0.34 mV). A substantial recovery was observed between 6 months and 2.5 years after the peripheral nerve injury. Stimulation of the sural (SU) nerve produced practically no PAD in muscle spindles from intact preparations, and this remained so in those afferents reconnected with muscle spindles impaled 2-12 weeks after the nerve crush. The mean amplitude of the PAD produced in afferent fibers reconnected with tendon organs by stimulation of the PBSt nerve and of the bulbar RF remained essentially the same as the PAD elicited in intact afferents. However, SU nerve stimulation produced a larger PAD in afferents

  7. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin.

    PubMed

    de Lartigue, Guillaume; de La Serre, Claire Barbier; Raybould, Helen E

    2011-11-30

    The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets.

  8. Multiple clusters of release sites formed by individual thalamic afferents onto cortical interneurons ensure reliable transmission.

    PubMed

    Bagnall, Martha W; Hull, Court; Bushong, Eric A; Ellisman, Mark H; Scanziani, Massimo

    2011-07-14

    Thalamic afferents supply the cortex with sensory information by contacting both excitatory neurons and inhibitory interneurons. Interestingly, thalamic contacts with interneurons constitute such a powerful synapse that even one afferent can fire interneurons, thereby driving feedforward inhibition. However, the spatial representation of this potent synapse on interneuron dendrites is poorly understood. Using Ca imaging and electron microscopy we show that an individual thalamic afferent forms multiple contacts with the interneuronal proximal dendritic arbor, preferentially near branch points. More contacts are correlated with larger amplitude synaptic responses. Each contact, consisting of a single bouton, can release up to seven vesicles simultaneously, resulting in graded and reliable Ca transients. Computational modeling indicates that the release of multiple vesicles at each contact minimally reduces the efficiency of the thalamic afferent in exciting the interneuron. This strategy preserves the spatial representation of thalamocortical inputs across the dendritic arbor over a wide range of release conditions.

  9. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin

    PubMed Central

    de Lartigue, Guillaume; de La Serre, Claire Barbier; Raybould, Helen E

    2011-01-01

    The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets. PMID:21376066

  10. Functional specializations of primary auditory afferents on the Mauthner cells: Interactions between membrane and synaptic properties

    PubMed Central

    Curti, Sebastian; Pereda, Alberto E.

    2009-01-01

    Primary auditory afferents are usually perceived as passive, timing-preserving, lines of communication. Contrasting this view, a special class of auditory afferents to teleost Mauthner cells, a command neuron that organizes tail-flip escape responses, undergoes potentiation of their mixed (electrical and chemical) synapses in response to high frequency cellular activity. This property is likely to represent a mechanism of input sensitization as these neurons provide the Mauthner cell with essential information for the initiation of an escape response. We review here the anatomical and physiological specializations of these identifiable auditory afferents. In particular, we discuss how their membrane and synaptic properties act in concert to more efficaciously activate the Mauthner cells. The striking functional specializations of these neurons suggest that primary auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized. PMID:19941953

  11. Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization.

    PubMed

    Olausson, Håkan; Cole, Jonathan; Rylander, Karin; McGlone, Francis; Lamarre, Yves; Wallin, B Gunnar; Krämer, Heidrun; Wessberg, Johan; Elam, Mikael; Bushnell, M Catherine; Vallbo, Ake

    2008-01-01

    In addition to A-beta fibres the human hairy skin has unmyelinated (C) fibres responsive to light touch. Previous functional magnetic resonance imaging (fMRI) studies in a subject with a neuronopathy who specifically lacks A-beta afferents indicated that tactile C afferents (CT) activate insular cortex, whereas no response was seen in somatosensory areas 1 and 2. Psychophysical tests suggested that CT afferents give rise to an inconsistent perception of weak and pleasant touch. By examining two neuronopathy subjects as well as control subjects we have now demonstrated that CT stimulation can elicit a sympathetic skin response. Further, the neuronopathy subjects' ability to localize stimuli which activate CT afferents was very poor but above chance level. The findings support the interpretation that the CT system is well suited to underpin affective rather than discriminative functions of tactile sensations.

  12. Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation in Calyx-Bearing Vestibular Afferents

    PubMed Central

    Kewin, Kevin; Jordan, Paivi M.; Cameron, Peter; Klapczynski, Marcin; McIntosh, J. Michael; Crooks, Peter A.; Dwoskin, Linda P.; Lysakowski, Anna

    2015-01-01

    Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton afferents. We recorded from CD and bouton afferents innervating the turtle posterior crista during electrical stimulation of vestibular efferents while applying several subtype-selective nAChR agonists and antagonists. The α9α10 nAChR antagonists, α-bungarotoxin and α-conotoxin RgIA, blocked efferent-mediated inhibition in bouton afferents while leaving efferent-mediated excitation in CD units largely intact. Conversely, 5-iodo-A-85380, sazetidine-A, varenicline, α-conotoxin MII, and bPiDDB (N,N-dodecane-1,12-diyl-bis-3-picolinium dibromide) blocked efferent-mediated excitation in CD afferents without affecting efferent-mediated inhibition in bouton afferents. This pharmacological profile suggested that calyceal nAChRs contain α6 and β2, but not α9, nAChR subunits. Selective blockade of efferent-mediated excitation in CD afferents distinguished dimorphic from calyx afferents by revealing type II hair cell input. Dimorphic afferents differed in having higher mean discharge rates and a mean efferent-mediated excitation that was smaller in amplitude yet longer in duration. Molecular biological data demonstrated the expression of α9 in turtle hair cells and α4 and β2 in associated vestibular ganglia. PMID:25716861

  13. Interneurones in pathways from group II muscle afferents in sacral segments of the feline spinal cord.

    PubMed

    Jankowska, E; Riddell, J S

    1994-03-15

    1. Properties of dorsal horn interneurones that process information from group II muscle afferents in the sacral segments of the spinal cord have been investigated in the cat using both intracellular and extracellular recording. 2. The interneurones were excited by group II muscle afferents and cutaneous afferents but not by group I muscle afferents. They were most effectively excited by group II afferents of the posterior biceps, semitendinosus, triceps surae and quadriceps muscle nerves and by cutaneous afferents running in the cutaneous femoris, pudendal and sural nerves. The earliest synaptic actions were evoked monosynaptically and were very tightly locked to the stimuli. 3. EPSPs evoked monosynaptically by group II muscle afferents and cutaneous afferents of the most effective nerves were often cut short by disynaptic IPSPs. As a consequence of this negative feedback the EPSPs gave rise to single or double spike potentials and only a minority of interneurones responded with repetitive discharges. However, the neurones that did respond repetitively did so at a very high frequency of discharges (0.8-1.2 ms intervals between the first 2-3 spikes). 4. Sacral dorsal horn group II interneurones do not appear to act directly upon motoneurones because: (i) these interneurones are located outside the area within which last order interneurones have previously been found and (ii) the latencies of PSPs evoked in motoneurones by stimulation of the posterior biceps and semitendinosus, cutaneous femoris and pudendal nerves (i.e. the main nerves providing input to sacral interneurones) are compatible with a tri- but not with a disynaptic coupling. Spatial facilitation of EPSPs and IPSPs following synchronous stimulation of group II and cutaneous afferents of these nerves shows, however, that sacral interneurones may induce excitation or inhibition of motoneurones via other interneurones. 5. Comparison of the properties of group II interneurones in the sacral segments with

  14. Receptive properties of myelinated primary afferents innervating the inflamed urinary bladder of the cat.

    PubMed

    Häbler, H J; Jänig, W; Koltzenburg, M

    1993-02-01

    1. The present study has investigated the receptive properties of myelinated mechanoreceptive primary afferents innervating the inflamed urinary bladder of the cat. In 15 experiments, 20 units were recorded from the dorsal and 3 from the ventral root S2. Before inflammation the afferents had no resting activity and responded consistently to increases of intravesical pressure evoked by isotonic distension or isovolumetric contractions. All units were studied before and after the onset of an acute inflammation induced by intraluminal injection of mustard (1-2.5%) or turpentine oil (50%), which are known to induce an acute cystitis. 2. Eleven out of 14 units tested with mustard oil and 5/9 units tested with turpentine oil were activated at short latency. The response could not be explained by a concomitant increase of intraluminal pressure resulting from the intravesical injection of the irritant. This suggests that a large proportion of mechanosensitive afferents has an additional chemosensitivity. 3. After removal of the irritants and with empty bladder, all afferent units exhibited irregular ongoing activity with intermittent high-frequency bursts. Such ongoing activity was entirely absent in myelinated afferents supplying the noninflamed bladder. The median rate of ongoing activity was significantly higher after mustard oil (1.65 imp/s) than after turpentine oil treatment (0.05 imp/s) 1 h after chemical stimulation. Post-hoc analysis revealed that afferents that developed high levels of ongoing activity had steeper stimulus response functions to changes of intravesical pressure before inflammation. 4. The stimulus-response function of vesical afferents changed characteristically in the inflamed bladder. Within 30 min of mustard oil treatment, the responses of some units to bladder filling was transiently enhanced, but later the units desensitized to this stimulus. However, there was no significant change of the stimulus-response function of six afferents studied

  15. Organization of hindlimb muscle afferent projections to lumbosacral motoneurons in the chick embryo.

    PubMed

    Lee, M T; O'Donovan, M J

    1991-08-01

    We have examined the organization of muscle afferent projections to motoneurons in the lumbosacral spinal cord of chick embryos between stage 37, when muscle afferents first reach the motor nucleus, and stage 44, which is just before hatching. Connectivity between afferents and motoneurons was assessed by stimulating individual muscle nerves and recording the resulting motoneuron synaptic potentials intracellularly or electrotonically from other muscle nerves. Most of the recordings were made in the presence of DL-2-amino-5-phosphonovaleric acid (APV), picrotoxin, and strychnine to block long-latency excitatory and inhibitory pathways. Activation of muscle afferents evoked slow, positive potentials in muscle nerves but not in cutaneous nerves. These potentials were abolished in 0 mM Ca2+, 2mM Mn2+ solutions, indicating that they were generated by the action of chemical synapses. The muscle nerve recordings revealed a wide-spread pattern of excitatory connections between afferents and motoneurons innervating six different thigh muscles, which were not organized according to synergist-antagonist relationships. This pattern of connectivity was confirmed using intracellular recording from identified motoneurons, which allowed the latency of the responses to be determined. Short-latency potentials in motoneurons were produced by activation of homonymous afferents and the heteronymous afferents innervating the hip flexors sartorius and anterior iliotibialis. Stimulation of anterior iliotibialis afferents also resulted in some short-latency excitatory postsynaptic potentials (EPSPs) in motoneurons innervating the knee extensor femorotibialis, though other connections were of longer latency. Afferents from the adductor, a hip extensor, did not evoke short-latency EPSPs in any of these three types of motoneurons. Short-latency, but not long-latency EPSPs, persisted during repetitive stimulation at 5 Hz, suggesting that they were mediated monosynaptically. Long

  16. Bladder afferent sensitivity in wild-type and TRPV1 knockout mice

    PubMed Central

    Daly, D; Rong, W; Chess-Williams, R; Chapple, C; Grundy, D

    2007-01-01

    Understanding bladder afferent pathways may reveal novel targets for therapy of lower urinary tract disorders such as overactive bladder syndrome and cystitis. Several potential candidate molecules have been postulated as playing a significant role in bladder function. One such candidate is the transient receptor potential vanilloid 1 (TRPV1) ion channel. Mice lacking the TRPV1 channel have altered micturition thresholds suggesting that TRPV1 channels may play a role in the detection of bladder filling. The aim of this study was therefore to investigate the role of TRPV1 receptors in controlling bladder afferent sensitivity in the mouse using pharmacological receptor blockade and genetic deletion of the channel. Multiunit afferent activity was recorded in vitro from bladder afferents taken from wild-type (TRPV+/+) mice and knockout (TRPV1−/−) mice. In wild-type preparations, ramp distension of the bladder to a maximal pressure of 40 mmHg produced a graded increase in afferent activity. Bath application of the TRPV1 antagonist capsazepine (10 μm) caused a significant attenuation of afferent discharge in TRPV1+/+ mice. Afferent responses to distension were significantly attenuated in TRPV1−/− mice in which sensitivity to intravesical hydrochloric acid (50 mm) and capsaicin (10 μm) were also blunted. Altered mechanosensitivity occurred in the absence of any changes in the pressure–volume relationship during filling indicating that this was not secondary to a change in bladder compliance. Single-unit analysis was used to classify individual afferents into low-threshold and high-threshold fibres. Low threshold afferent responses were attenuated in TRPV1−/− mice compared to the TRPV1+/+ littermates while surprisingly high threshold afferent sensitivity was unchanged. While TRPV1 channels are not considered to be mechanically gated, the present study demonstrates a clear role for TRPV1 in the excitability of particularly low threshold bladder afferents

  17. Efferent and afferent evoked potentials in patients with adrenomyeloneuropathy.

    PubMed

    Matsumoto, Hideyuki; Hanajima, Ritsuko; Terao, Yasuo; Hamada, Masashi; Yugeta, Akihiro; Shirota, Yuichiro; Yuasa, Kaoru; Sato, Fumio; Matsukawa, Takashi; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji; Ugawa, Yoshikazu

    2010-02-01

    This paper investigates efferent and afferent conductions of the central nervous system by various evoked potentials in patients with adrenomyeloneuropathy (AMN). Ten pure AMN patients without cerebral involvement were studied. Motor evoked potentials (MEPs), somatosensory evoked potentials (SEPs), auditory brainstem response (ABR), and pattern reversal full-field visual evoked potentials (VEPs) were recorded. For MEP recording, single-pulse or double-pulse magnetic brainstem stimulation (BST) was also performed. Abnormal MEP was observed in all ten patients, abnormal SEP in all ten, abnormal ABR in nine, and abnormal VEP in only one. Brainstem latency was measured in three of the seven patients with central motor conduction time (CMCT) prolongation. The cortical-brainstem conduction time was severely prolonged along the normal or mildly delayed brainstem-cervical conduction time in those three patients. The pattern of normal VEP and abnormal MEP, SEP, ABR is a clinically useful electrophysiological feature for the diagnosis. BST techniques are helpful to detect, functionally, intracranial corticospinal tract involvement, probably demyelination, in pure AMN patients. 2009 Elsevier B.V. All rights reserved.

  18. Dynamic GABAergic afferent modulation of AgRP neurons

    PubMed Central

    Garfield, Alastair S; Shah, Bhavik P; Burgess, Christian R; Li, Monica M; Li, Chia; Steger, Jennifer S; Madara, Joseph C; Campbell, John N; Kroeger, Daniel; Scammell, Thomas E; Tannous, Bakhos A; Myers, Martin G; Andermann, Mark L; Krashes, Michael J; Lowell, Bradford B

    2017-01-01

    Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues prior to ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior. PMID:27643429

  19. Linear Path Integration Deficits in Patients with Abnormal Vestibular Afference

    PubMed Central

    Arthur, Joeanna C.; Kortte, Kathleen B.; Shelhamer, Mark; Schubert, Michael C.

    2014-01-01

    Effective navigation requires the ability to keep track of one’s location and maintain orientation during linear and angular displacements. Path integration is the process of updating the representation of body position by integrating internally-generated self-motion signals over time (e.g., walking in the dark). One major source of input to path integration is vestibular afference. We tested patients with reduced vestibular function (unilateral vestibular hypofunction, UVH), patients with aberrant vestibular function (benign paroxysmal positional vertigo, BPPV), and healthy participants (controls) on two linear path integration tasks: experimenter-guided walking and target-directed walking. The experimenter-guided walking task revealed a systematic underestimation of self-motion signals in UVH patients compared to the other groups. However, we did not find any difference in the distance walked between the UVH group and the control group for the target-directed walking task. Results from neuropsychological testing and clinical balance measures suggest that the errors in experimenter-guided walking were not attributable to cognitive and/or balance impairments. We conclude that impairment in linear path integration in UVH patients stem from deficits in self-motion perception. Importantly, our results also suggest that patients with a UVH deficit do not lose their ability to walk accurately without vision to a memorized target location. PMID:22726251

  20. Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans.

    PubMed

    Helmich, R C G; Bäumer, T; Siebner, H R; Bloem, B R; Münchau, A

    2005-11-01

    A conditioning electrical stimulus to a digital nerve can inhibit the motor-evoked potentials (MEPs) in adjacent hand muscles elicited by transcranial magnetic stimulation (TMS) to the contralateral primary motor cortex (M1) when given 25-50 ms before the TMS pulse. This is referred to as short-latency afferent inhibition (SAI). We studied inter-hemispheric differences (Experiment 1) and within-limb somatotopy (Experiment 2) of SAI in healthy right-handers. In Experiment 1, conditioning electrical pulses were applied to the right or left index finger (D2) and MEPs were recorded from relaxed first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles ipsilateral to the conditioning stimulus. We found that SAI was more pronounced in right hand muscles. In Experiment 2, electrical stimulation was applied to the right D2 and MEPs were recorded from ipsilateral FDI, extensor digitorum communis (EDC) and biceps brachii (BB) muscles. The amount of SAI did not differ between FDI, EDC and BB muscles. These data demonstrate inter-hemispheric differences in the processing of cutaneous input from the hand, with stronger SAI in the dominant left hemisphere. We also found that SAI occurred not only in hand muscles adjacent to electrical digital stimulation, but also in distant hand and forearm and also proximal arm muscles. This suggests that SAI induced by electrical D2 stimulation is not focal and somatotopically specific, but a more widespread inhibitory phenomenon.

  1. Respiratory motor responses to cranial nerve afferent stimulation in rats.

    PubMed

    Hayashi, F; McCrimmon, D R

    1996-10-01

    It was hypothesized that, because rats appear to lack a prominent disynaptic projection from the dorsal respiratory group to phrenic motoneurons (Phr), they would lack the short-latency excitation of Phr output seen in cats in response to stimulation of some cranial nerve afferents. Single-pulse superior laryngeal nerve (SLN) stimulation elicited a short-latency bilateral excitation of glossopharyngeal (IX) and hypoglossal (XII) nerves and an ipsilateral excitation of pharyngeal branch of vagus (PhX) in 67% of rats, but no excitation of Phr. Vagus (X) stimulation elicited a bilateral excitation of Phr and a predominantly ipsilateral excitation of IX and PhX. Single-pulse stimulation of SLN or X also elicited longer-latency, bilateral decreases in activity of all recorded nerves. Repetitive stimulation (50 Hz) of SLN or X suppressed inspiratory activity and prolonged expiration. Lung inflation (7.5 cmH2O) inhibited Phr and PhX activity; X stimulation inhibited Phr but prolonged PhX activity. In conclusion, rats predictably lack the SLN-induced short latency Phr excitation but exhibit other short latency reflexes for which the underlying circuitry is not clear.

  2. Evidence that the Tritonia diomedea Swim Afferent Neurons Are Glutamatergic

    PubMed Central

    Megalou, E.V.; Brandon, C.J.; Frost, W.N.

    2011-01-01

    The escape swim response of the marine mollusc Tritonia diomedea is a well-established model system for studies of the neural basis of behavior. While the swim neural network is reasonably well understood, little is known about the transmitters used by its constituent neurons. In the present study, we provide immunocytochemical and electrophysiological evidence that the S-cells, the afferent neurons that detect aversive skin stimuli and in turn trigger Tritonia’s escape swim response, use glutamate as their transmitter. First, immunolabeling revealed that S-cell somata contain elevated levels of glutamate compared to most other neurons in the Tritonia brain, consistent with findings from glutamatergic neurons in many species. Second, pressure-applied puffs of glutamate produced the same excitatory response in the target neurons of the S-cells as the naturally released S-cell transmitter itself. Third, the glutamate receptor antagonist CNQX completely blocked S-cell synaptic connections. These findings support glutamate as a transmitter used by the S-cells, and will facilitate studies using this model system to explore a variety of issues related to the neural basis of behavior. PMID:19366921

  3. Afferent input regulates the formation of distal dendritic branches.

    PubMed

    Mizrahi, Adi; Libersat, Frederic

    2002-10-07

    During postembryonic development, the dendritic arbors of neurons grow to accommodate new incoming synaptic inputs. Our goal was to examine which features of dendritic architecture of postsynaptic interneurons are regulated by these synaptic inputs. To address this question, we took advantage of the cockroach cercal system where the morphology of the sensory giant interneurons (GIs) is uniquely identified and, therefore, amenable to quantitative analysis. We analyzed the three-dimensional architecture of chronically deafferented vs. normally developed dendritic trees of a specific identified GI, namely GI2. GI2 shows five prominent dendrites, four of which were significantly altered after deafferentation. De-afferentation induced an average of 55% decrease in metric measures (number of branch points, total length, and total surface area) on the entire dendritic tree. Sholl and branch order analysis showed a decrease in the most distal and higher order branches. We suggest that afferent input plays a specific role in shaping the morphology of dendritic trees by regulating the formation or maintenance of high-order distal branches.

  4. Afference copy as a quantitative neurophysiological model for consciousness.

    PubMed

    Cornelis, Hugo; Coop, Allan D

    2014-06-01

    Consciousness is a topic of considerable human curiosity with a long history of philosophical analysis and debate. We consider there is nothing particularly complicated about consciousness when viewed as a necessary process of the vertebrate nervous system. Here, we propose a physiological "explanatory gap" is created during each present moment by the temporal requirements of neuronal activity. The gap extends from the time exteroceptive and proprioceptive stimuli activate the nervous system until they emerge into consciousness. During this "moment", it is impossible for an organism to have any conscious knowledge of the ongoing evolution of its environment. In our schematic model, a mechanism of "afference copy" is employed to bridge the explanatory gap with consciously experienced percepts. These percepts are fabricated from the conjunction of the cumulative memory of previous relevant experience and the given stimuli. They are structured to provide the best possible prediction of the expected content of subjective conscious experience likely to occur during the period of the gap. The model is based on the proposition that the neural circuitry necessary to support consciousness is a product of sub/preconscious reflexive learning and recall processes. Based on a review of various psychological and neurophysiological findings, we develop a framework which contextualizes the model and briefly discuss further implications.

  5. Blunting of rapid onset vasodilatation and blood flow restriction in arterioles of exercising skeletal muscle with ageing in male mice.

    PubMed

    Jackson, Dwayne N; Moore, Alex W; Segal, Steven S

    2010-06-15

    Exercise capacity and skeletal muscle blood flow are diminished with ageing but little is known of underlying changes in microvascular haemodynamics. Further, it is not clear how the sympathetic nervous system affects the microcirculation of skeletal muscle with ageing or whether sex differences prevail in the regulation of arteriolar diameter in response to muscle contractions. In the gluteus maximus muscle of C57BL/6 mice, we tested the hypothesis that ageing would impair 'rapid onset vasodilatation' (ROV) in distributing arterioles (second-order, 2A) of old (20-month) males (OM) and females (OF) relative to young (3-month) males (YM) and females (YF). Neither resting (approximately 17 microm) nor maximum (approximately 30 microm) 2A diameters differed between groups. In response to single tetanic contractions at 100 Hz (duration, 100-1000 ms), ROV responses were blunted by half in OM relative to OF, YM or YF. With no effect in YM, blockade of alpha-adrenoreceptors with phentolamine (1 mum) restored ROV in OM. Topical noradrenaline (1 nM) blunted ROV in YM and YF to levels seen in OM and further suppressed ROV in OM (P < 0.05). To evaluate arteriolar blood flow, red blood cell velocity was measured in 2A of OM and YM; respective heart rates (353 +/- 22 vs. 378 +/- 15 beats min(1)) and carotid arterial blood pressures (76 +/- 3 vs. 76 +/- 1 mmHg) were not different. Blood flows at rest (0.6 +/- 0.1 vs. 1.6 +/- 0.2 nl s(1)) and during maximum dilatation (2.0 +/- 0.8 vs. 5.4 +/- 0.8 nl s(1)) with sodium nitroprusside (10 microM) were attenuated >60% (P < 0.05) in OM. Blood flow at peak ROV was blunted by 75-80% in OM vs. YM (P < 0.05). In response to 30 s of rhythmic contractions at 2, 4 and 8 Hz, progressive dilatations did not differ with age or sex. Nevertheless, resting and peak blood flows in YM were 2- to 3-fold greater (P < 0.05) than OM. We suggest that ageing blunts ROV and restricts blood flow to skeletal muscle of OM through subtle activation of alpha

  6. Blunting of rapid onset vasodilatation and blood flow restriction in arterioles of exercising skeletal muscle with ageing in male mice

    PubMed Central

    Jackson, Dwayne N; Moore, Alex W; Segal, Steven S

    2010-01-01

    Exercise capacity and skeletal muscle blood flow are diminished with ageing but little is known of underlying changes in microvascular haemodynamics. Further, it is not clear how the sympathetic nervous system affects the microcirculation of skeletal muscle with ageing or whether sex differences prevail in the regulation of arteriolar diameter in response to muscle contractions. In the gluteus maximus muscle of C57BL/6 mice, we tested the hypothesis that ageing would impair ‘rapid onset vasodilatation’ (ROV) in distributing arterioles (second-order, 2A) of old (20-month) males (OM) and females (OF) relative to young (3-month) males (YM) and females (YF). Neither resting (∼17 μm) nor maximum (∼30 μm) 2A diameters differed between groups. In response to single tetanic contractions at 100 Hz (duration, 100–1000 ms), ROV responses were blunted by half in OM relative to OF, YM or YF. With no effect in YM, blockade of α-adrenoreceptors with phentolamine (1 μm) restored ROV in OM. Topical noradrenaline (1 nm) blunted ROV in YM and YF to levels seen in OM and further suppressed ROV in OM (P < 0.05). To evaluate arteriolar blood flow, red blood cell velocity was measured in 2A of OM and YM; respective heart rates (353 ± 22 vs. 378 ± 15 beats min−1) and carotid arterial blood pressures (76 ± 3 vs. 76 ± 1 mmHg) were not different. Blood flows at rest (0.6 ± 0.1 vs. 1.6 ± 0.2 nl s−1) and during maximum dilatation (2.0 ± 0.8 vs. 5.4 ± 0.8 nl s−1) with sodium nitroprusside (10 μm) were attenuated >60% (P < 0.05) in OM. Blood flow at peak ROV was blunted by 75–80% in OM vs. YM (P < 0.05). In response to 30 s of rhythmic contractions at 2, 4 and 8 Hz, progressive dilatations did not differ with age or sex. Nevertheless, resting and peak blood flows in YM were 2- to 3-fold greater (P < 0.05) than OM. We suggest that ageing blunts ROV and restricts blood flow to skeletal muscle of OM through subtle activation of α-adrenoreceptors in microvascular

  7. Quantitative Analysis of Mouse Dural Afferent Neurons Expressing TRPM8, VGLUT3, and NF200.

    PubMed

    Ren, Lynn; Chang, Michelle Jaehee; Zhang, Zhiyu; Dhaka, Ajay; Guo, Zhaohua; Cao, Yu-Qing

    2017-09-19

    To quantify the abundance of dural afferent neurons expressing transient receptor potential channel melastatin 8 (TRPM8), vesicular glutamate transporter 3 (VGLUT3), and neurofilament 200 (NF200) in adult mice. With the increasing use of mice as a model system to study headache mechanisms, it is important to understand the composition of dural afferent neurons in mice. In a previous study, we have measured the abundance of mouse dural afferent neurons that express neuropeptide calcitonin gene-related peptide as well as two TRP channels TRPV1 and TRPA1, respectively. Here, we conducted quantitative analysis of three other dural afferent subpopulations in adult mice. We used the fluorescent tracer Fluoro-Gold to retrogradely label dural afferent neurons in adult mice expressing enhanced green fluorescent protein in discrete subpopulations of trigeminal ganglion (TG) neurons. Mechanoreceptors with myelinated fibers were identified by NF200 immunoreactivity. We also conducted Ca(2+) -imaging experiments to test the overlap between TRPM8 and VGLUT3 expression in mouse primary afferent neurons (PANs). The abundance of TRPM8-expressing neurons in dural afferent neurons was significantly lower than that in total TG neurons. The percentages of dural afferent neurons expressing VGLUT3 and NF200 were comparable to those of total TG neurons, respectively. TRPM8 agonist menthol evoked Ca(2+) influx in less than 7% VGLUT3-expressing PANs in adult mice. TG neurons expressing TRPM8, VGLUT3, and NF200 all innervate adult mouse dura. TRPM8 and VGLUT3 are expressed in distinct subpopulations of PANs in adult mice. These results provide an anatomical basis to investigate headache mechanisms in mouse models. © 2017 American Headache Society.

  8. Conduction Properties Distinguish Unmyelinated Sympathetic Efferent Fibers and Unmyelinated Primary Afferent Fibers in the Monkey

    PubMed Central

    Ringkamp, Matthias; Johanek, Lisa M.; Borzan, Jasenka; Hartke, Timothy V.; Wu, Gang; Pogatzki-Zahn, Esther M.; Campbell, James N.; Shim, Beom; Schepers, Raf J.; Meyer, Richard A.

    2010-01-01

    Background Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves. Methodology/Principal Findings In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively. In centrifugal recordings, electrical stimulation at the sympathetic chain and dorsal root was used to determine the fiber's origin. In centrifugal recordings, sympathetic fibers exhibited absolute speeding of conduction to a single pair of electrical stimuli separated by 50 ms; the second action potential was conducted faster (0.61 0.16%) than the first unconditioned action potential. This was never observed in primary afferents. Following 2 Hz stimulation (3 min), activity-dependent slowing of conduction in the sympathetics (8.6 0.5%) was greater than in one afferent group (6.7 0.5%) but substantially less than in a second afferent group (29.4 1.9%). In centripetal recordings, most mechanically-insensitive fibers also exhibited absolute speeding to twin pulse stimulation. The subset that did not show this absolute speeding was responsive to chemical stimuli (histamine, capsaicin) and likely consists of mechanically-insensitive afferents. During repetitive twin pulse stimulation, mechanosensitive afferents developed speeding, and speeding in sympathetic fibers increased. Conclusions/Significance The presence of absolute speeding provides a criterion by which sympathetic efferents can be differentiated from primary afferents. The differences in conduction properties between sympathetics and afferents likely reflect differential expression of voltage-sensitive ion channels. PMID:20140089

  9. Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons

    PubMed Central

    Wu, Shaw-wen; Lindberg, Jonathan E. M.

    2016-01-01

    Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3−/−1 mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1. PMID:26843581

  10. Input-output functions of vestibular afferent responses to air-conducted clicks in rats.

    PubMed

    Zhu, Hong; Tang, Xuehui; Wei, Wei; Maklad, Adel; Mustain, William; Rabbitt, Richard; Highstein, Steve; Allison, Jerome; Zhou, Wu

    2014-02-01

    Sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid muscles (the cervical vestibular-evoked myogenic potential or cVEMP) and the extraocular muscles (the ocular VEMP or oVEMP) have proven useful in clinical assessment of vestibular function. VEMPs are commonly interpreted as a test of saccular function, based on neurophysiological evidence showing activation of saccular afferents by intense acoustic click stimuli. However, recent neurophysiological studies suggest that the clicks used in clinical VEMP tests activate vestibular end organs other than the saccule. To provide the neural basis for interpreting clinical VEMP testing results, the present study examined the extent to which air-conducted clicks differentially activate the various vestibular end organs at several intensities and durations in Sprague-Dawley rats. Single unit recordings were made from 562 vestibular afferents that innervated the otoliths [inferior branch otolith (IO) and superior branch otolith (SO)], the anterior canal (AC), the horizontal canal (HC), and the posterior canal (PC). Clicks higher than 60 dB SL (re-auditory brainstem response threshold) activated both semicircular canal and otolith organ afferents. Clicks at or below 60 dB SL, however, activated only otolith organ afferents. Longer duration clicks evoked larger responses in AC, HC, and SO afferents, but not in IO afferents. Intra-axonal recording and labeling confirmed that sound sensitive vestibular afferents innervated the horizontal and anterior canal cristae as well as the saccular and utricular maculae. Interestingly, all sound sensitive afferents are calyx-bearing fibers. These results demonstrate stimulus-dependent acoustic activation of both semicircular canals and otolith organs, and suggest that sound activation of vestibular end organs other than the saccule should not be ruled out when designing and interpreting clinical VEMP tests.

  11. Fusimotor reflexes in relaxed forearm muscles produced by cutaneous afferents from the human hand.

    PubMed Central

    Gandevia, S C; Wilson, L; Cordo, P J; Burke, D

    1994-01-01

    1. This study was designed to determine whether cutaneous receptors in the hand exert reflex effects on fusimotor neurones innervating relaxed muscles. Recordings were made from fifty-four muscle spindle afferents in the radial nerve while the arm was held relaxed in a supporting frame. Cutaneous afferents were activated by trains of stimuli at non-noxious levels to the superficial radial nerve or to the palmar surface of the fingers. 2. For the population of muscle spindle afferents, the mean discharge rate was 7.1 +/- 6.4 Hz (range 0-24 Hz). Thirty-three per cent had no background discharge, and this occurred significantly more often in finger extensors than wrist extensors. 3. Trains of cutaneous stimuli produced no change in the discharge rates of the majority of spindle endings irrespective of whether the spindle afferent had a background discharge or was given one by muscle stretch. However, with two of forty afferents, the stimuli produced an increase in discharge at latencies of 135 and 155 ms. 4. With a further fourteen muscle spindle endings, the dynamic responses to stretch were measured 100-400 ms after the trains of cutaneous stimuli. For four spindle afferents there was a statistically significant change in the dynamic response to stretch occurring at conditioned-stretch intervals of 100-200 ms. For two afferents the dynamic response decreased by 17 and 26% and for two others it increased by about 24 and 37%. 5. While these results support the view that the level of background fusimotor drive is low in the relaxed state, they suggest that there is some dynamic fusimotor drive to completely relaxed muscles operating on the human hand, and that this drive can be altered reflexly by cutaneous afferent inputs from the hand. Images Figure 4 PMID:7837105

  12. External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1

    PubMed Central

    Largent-Milnes, Tally M.; Fawley, Jessica A.; Andresen, Michael C.

    2014-01-01

    The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 μM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1− ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1− inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents. PMID:25185814

  13. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2014-10-01

    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

  14. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine

    PubMed Central

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J.; Mikami, Dean J.

    2014-01-01

    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca2+ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals. PMID:25147231

  15. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice.

    PubMed

    Feng, Bin; La, Jun-Ho; Tanaka, Takahiro; Schwartz, Erica S; McMurray, Timothy P; Gebhart, G F

    2012-10-01

    Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15-60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were conducted on both TNBS and saline-treated mice to assess colorectal afferent function. Mice exhibited significant colorectal hypersensitivity through day 14 after TNBS treatment that resolved by day 28 with no resensitization through day 56. TNBS induced a neutrophil- and macrophage-based colorectal inflammation as well as loss of nerve fibers, all of which resolved by days 14-28. Single-fiber recordings revealed a net increase in afferent drive from stretch-sensitive colorectal afferents at day 14 post-TNBS and reduced proportions of mechanically insensitive afferents (MIAs) at days 14-28. Intracolonic TNBS-induced colorectal inflammation was associated with the development and recovery of hypersensitivity in mice, which correlated with a transient increase and recovery of sensitization of stretch-sensitive colorectal afferents and MIAs. These results indicate that the development and maintenance of colorectal hypersensitivity following inflammation are mediated by peripheral drive from stretch-sensitive colorectal afferents and a potential contribution from MIAs.

  16. Termination of electroreceptor and mechanical lateral line afferents in the mormyrid acousticolateral area.

    PubMed

    Bell, C C; Russell, C J

    1978-12-01

    The projection regions of electroreceptor and mechanical lateral line afferents in electric fish of the mormyridae family are described. Electroreceptor afferents from the posterior dorsal skin run in the dorsal branch of the posterior lateral line nerve. Electroreceptor afferents from ventral skin and mechanical lateral line afferents and efferents run in the ventral branch of the nerve. Horseradish peroxidase (HRP) injections into each branch resulted in filling of its central terminals with the marker enzyme. The method yields a Golgi-like staining of afferent terminals, allowing some aspects of their morphology to be described. Comparison of results from dorsal and ventral branch injections shows the separate medullary regions to which electroreceptor and mechanical afferents project, and also demonstrates four separate somatotopic maps within the electroreceptor region. Mechanical afferents end predominantly ipsilaterally in nucleus anterior and eminentia granularis as has been suggested by others. Ipsilateral endings in nucleus octavius are also seen. Electroreceptor afferents end exclusively in the cortex and nucleus of posterior lateral line lobe (PLLL). Within the cortex there are three distinct maps of the skin surface which are separated from each other by discontinuities in the cellular layers. Somatotopic mapping is also present in the nucleus of PLLL though it is less precise than in the cortical zones. Large club endings of the cells of this nucleus are filled with HRP. Labeled cells are seen within a small midline nucleus located at the level of the eighth nerve just above the medial longitudinal fasciculus. These are probably the cell bodies of lateral line efferents.

  17. Endoscopic removal of an enterolith causing afferent loop syndrome using electrohydraulic lithotripsy.

    PubMed

    Kim, Hwa Jong; Moon, Jong Ho; Choi, Hyun Jong; Koo, Hyun Cheol; Park, Sung Jin; Cheon, Young Koog; Cho, Young Deok; Lee, Moon Sung; Shim, Chan Sup

    2010-07-01

    Electrohydraulic lithotripsy is a very useful method for fragmenting biliary stones and it can be used for endoscopic removal of difficult biliary stones. Acute afferent loop syndrome induced by enterolith is very rare, and surgical treatment is the usual choice for this condition. We describe a patient with acute afferent loop syndrome, which was induced by an enterolith after a Billroth II gastrectomy. We used electrohydraulic lithotripsy to endoscopically remove the enterolith.

  18. Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo

    PubMed Central

    2013-01-01

    Background ATP-sensitive K+ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca2+ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO2. Results Change from “high” oxygen tension (PO2 = 153.4 ± 3.4 mmHg) to “low” oxygen tension (PO2 = 13.8 ± 1.3 mmHg) dilated cremaster muscle arterioles from 11.0 ± 0.4 μm to 32.9 ± 0.9 μm (n = 28, P < 0.05). Glibenclamide (KATP channel blocker) caused maximal vasoconstriction, and abolished the dilation to low oxygen, whereas the KATP channel opener cromakalim caused maximal dilation and prevented the constriction to high oxygen. When adding cromakalim on top of glibenclamide or vice versa, the reactivity to oxygen was gradually restored. Inhibition of L-type Ca2+ channels using 3 μM nifedipine did not fully block basal tone in the arterioles, but rendered them unresponsive to changes in PO2. Inhibition of the CYP450-4A enzyme using DDMS blocked vasoconstriction to an increase in PO2, but had no effect on dilation to low PO2. Conclusions We conclude that: 1) L-type Ca2+ channels are central to oxygen sensing, 2) KATP channels are permissive for the arteriolar response to oxygen, but are not directly involved in the oxygen sensing mechanism and 3) CYP450-4A mediated 20-HETE production is involved in vasoconstriction to high PO2. PMID:23663730

  19. Permanent reorganization of Ia afferent synapses on motoneurons after peripheral nerve injuries

    PubMed Central

    Alvarez, Francisco J.; Bullinger, Katie L.; Titus, Haley E.; Nardelli, Paul; Cope, Timothy C.

    2010-01-01

    After peripheral nerve injuries to a motor nerve the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons. PMID:20536938

  20. The role of the renal afferent and efferent nerve fibers in heart failure

    PubMed Central

    Booth, Lindsea C.; May, Clive N.; Yao, Song T.

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

  1. FMRFamide-related peptide expression in the vestibular-afferent neurons.

    PubMed

    Mercado, Francisco; López, Iván; Ortega, Aida; Almanza, Angélica; Soto, Enrique; Vega, Rosario

    2012-03-28

    Vestibular-afferent neurons innervate hair cells from the sensory epithelia of vestibular end-organs and their action-potential discharge dynamics are driven by linear and angular accelerations of the head. The electrical activity of the vestibular-afferent neurons depends on their intrinsic properties and on the synaptic input from hair cells and from the terminals of the efferent system. Here we report that vestibular-afferent neurons of the rat are immunoreactive to RFamide-related peptides, and that the stronger signal comes from calyx-shaped neuron dendrites, with no signal detected in hair cells or supporting cells. The whole-cell voltage clamp recording of isolated afferent neurons showed that they express robust acid-sensing ionic currents (ASICs). Extracellular multiunit recordings of the vestibular nerve in a preparation in vitro of the rat inner ear showed that the perfusion of FMRFamide (a snail ortholog of this family of neuropeptides) exerts an excitatory effect on the afferent-neurons spike-discharge rate. Because the FMRFamide cannot activate the ASIC but reduces its desensitization generating a more robust current, its effect indicates that the ASIC are tonically active in the vestibular-afferent neurons and modulated by RFamide-like peptides.

  2. The role of the renal afferent and efferent nerve fibers in heart failure.

    PubMed

    Booth, Lindsea C; May, Clive N; Yao, Song T

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF.

  3. Coarse topographic organization of pheromone-sensitive afferents from different antennal surfaces in the American cockroach.

    PubMed

    Nishino, Hiroshi; Watanabe, Hidehiro; Kamimura, Itsuro; Yokohari, Fumio; Mizunami, Makoto

    2015-05-19

    In contrast to visual, auditory, taste, and mechanosensory neuropils, in which sensory afferents are topographically organized on the basis of their peripheral soma locations, axons of cognate sensory neurons from different locations of the olfactory sense organ converge onto a small spherical neuropil (glomerulus) in the first-order olfactory center. In the cockroach Periplaneta americana, sex pheromone-sensitive afferents with somata in the antero-dorsal and postero-ventral surfaces of a long whip-like antenna are biased toward the anterior and posterior regions of a macroglomerulus, respectively. In each region, afferents with somata in the more proximal antenna project to more proximal region, relative to the axonal entry points. However, precise topography of afferents in the macroglomerulus has remained unknown. Using single and multiple neuronal stainings, we showed that afferents arising from anterior, dorsal, ventral and posterior surfaces of the proximal regions of an antenna were biased progressively from the anterior to posterior region of the macroglomerulus, reflecting chiasmatic axonal re-arrangements that occur immediately before entering the antennal lobe. Morphologies of individual afferents originating from the proximal antenna matched results of mass neuronal stainings, but their three-dimensional origins in the antenna were hardly predictable on the basis of the projection patterns. Such projection biases made by neuronal populations differ from strict somatotopic projections of antennal mechanosensory neurons in the same species, suggesting a unique sensory mechanism to process information about odor location and direction on a single antenna.

  4. Three-dimensional head angular velocity detection from otolith afferent signals.

    PubMed

    Hess, B J

    1992-01-01

    Afferent signals from the otolith organs can produce compensatory eye position and velocity signals which has been described as linear vestibulo-ocular reflex (LVOR). The afferent otolith signals carry information about head orientation and changes of head orientation relative to gravity. A head orientation (tilt) related position signal can be obtained from population vector coding of tonic otolith afferent signals during static or dynamic head tilts, which in turn could produce compensatory eye position signals in the LVOR. On the other hand, eye angular velocity signals may be extracted, as proposed in this study, from the population response of tilt-velocity sensitive otolith afferents. Such afferents are shown to encode instantaneous head orientation relative to gravity at onset of a head movement and, as the movement continues, the projection of head angular velocity onto the earth-horizontal plane, indicating the instantaneous direction of movement relative to gravity. Angular velocity components along the earth-vertical direction which are not directly encoded by otolith afferents can be detected by central signal processing. Central reconstruction of 3D head angular velocity allows to obtain information about absolute head orientation in space even in the absence of semi-circular canal related information. Such information is important for generating compensatory eye movements as well as for dynamic control of posture.

  5. Classification of longissimus lumborum muscle spindle afferents in the anaesthetized cat.

    PubMed

    Durbaba, R; Taylor, A; Ellaway, P H; Rawlinson, S

    2006-03-01

    Recordings have been made from 127 single muscle spindle afferents from the longissimus lumborum muscles of anaesthetized cats. They have been characterized by their responses to passive muscle stretch and the effects of succinylcholine (SCh) and by their sensitivity to vibration. The use of SCh permitted the assessment for each afferent of the influence of bag1 (b1) and bag2 (b2) intrafusal muscle fibres. From this, on the assumption that all afferents were affected by chain (c) fibres, they were classified in four groups: b1b2c (41.9%), b2c (51.4%), b1c (1.3%) and c (5.4%). All the afferents with b1 influence were able to respond one to one to vibration at frequencies above 100 Hz and were considered to belong to primary endings. On the basis of the vibration test, 64% of the b2c type afferents appeared to be primaries and 36% secondaries. Of the units classified as primaries, 41% were designated as b2c and would not therefore be able to respond to dynamic fusimotor activity. The significance of this relatively high proportion of b2c-type spindle primary afferents is discussed in relation to the specialized postural function of the back muscles.

  6. Sensitizing effects of lafutidine on CGRP-containing afferent nerves in the rat stomach

    PubMed Central

    Nishihara, Katsushi; Nozawa, Yoshihisa; Nakano, Motoko; Ajioka, Hirofusa; Matsuura, Naosuke

    2002-01-01

    Capsaicin sensitive afferent nerves play an important role in gastric mucosal defensive mechanisms. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP), which seems to be the predominant neurotransmitter of spinal afferents in the rat stomach, exerting many pharmacological effects by a direct mechanism or indirectly through second messengers such as nitric oxide (NO). Lafutidine is a new type of anti-ulcer drug, possessing both an antisecretory effect, exerted via histamine H2 receptor blockade, and gastroprotective activities. Studies with certain antagonists or chemical deafferentation techniques suggest the gastroprotective actions of lafutidine to be mediated by capsaicin sensitive afferent nerves, but this is an assumption based on indirect techniques. In order to explain the direct relation of lafutidine to afferent nerves, we conducted the following studies. We determined CGRP and NO release from rat stomach and specific [3H]-resiniferatoxin (RTX) binding to gastric vanilloid receptor subtype 1 (VR1), which binds capsaicin, using EIA, a microdialysis system and a radioreceptor assay, respectively. Lafutidine enhanced both CGRP and NO release from the rat stomach induced by a submaximal dose of capsaicin, but had no effect on specific [3H]-RTX and capsaicin binding to VR1. In conclusion, our findings demonstrate that lafutidine modulates the activity of capsaicin sensitive afferent nerves in the rat stomach, which may be a key mechanism involved in its gastroprotective action. PMID:11906962

  7. Role of TRPV1 in high-threshold rat colonic splanchnic afferents is revealed by inflammation.

    PubMed

    Phillis, Benjamin D; Martin, Chris M; Kang, Daiwu; Larsson, Håkan; Lindström, Erik A; Martinez, Vicente; Blackshaw, L Ashley

    2009-08-07

    The vanilloid-1 receptor TRPV1 is known to play a role in extrinsic gastrointestinal afferent function. We investigated the role of TRPV1 in mechanosensitivity in afferents from normal and inflamed tissue. Colonic mechanosensitivity was determined in an in vitro rat colon preparation by recording from attached splanchnic nerves. Recordings were made from serosal/mesenteric afferents responding only at high thresholds to graded mechanical stimulation with von Frey probes. Colonic inflammation was induced by adding 5% dextran sulphate sodium (DSS) to the drinking water for 5 days, and was confirmed by histopathology. The selective TRPV1 antagonist, SB-750364 (10(-8) to 10(-6)M), was tested on mechanosensory stimulus response functions of afferents from normal and inflamed preparations (N=7 each). Mechanosensory responses had thresholds of 1-2g, and maximal responses were observed at 12 g. The stimulus response function was not affected by DSS-induced colitis. SB-750364 had no effect on stimulus response functions in normal preparations, but reduced (up to 60%) in a concentration-dependent manner those in inflammation (2-way ANOVA, p<0.05). Moreover, in inflamed tissue, spontaneous afferent activity showed a dose-dependent trend toward reduction with SB-750364. We conclude that mechanosensitivity of high-threshold serosal colonic splanchnic afferents to graded stimuli is unaffected during DSS colitis. However, there is a positive influence of TRPV1 in mechanosensitivity in inflammation, suggesting up-regulation of excitatory TRPV1-mediated mechanisms.

  8. Activation of vagal afferents in the rat duodenum by protein digests requires PepT1.

    PubMed

    Darcel, N P; Liou, A P; Tomé, D; Raybould, H E

    2005-06-01

    Intestinal infusion of protein digests activates a vago-vagal reflex inhibition of gastric motility. Protein digests release cholecystokinin (CCK) from enteroendocrine cells; however, the precise cellular mechanisms leading to vagal afferent activation is unclear. The hypothesis that the oligopeptide transporter PepT1 plays a major role in the initiation of this vago-vagal reflex was tested by recording activation of duodenal vagal afferent activity and inhibition of gastric motility in response to protein hydrolysates in the presence of 4-aminomethylbenzoic acid (4-AMBA), a competitive inhibitor of PepT1, or 4-aminophenylacetic acid (4-APAA), an inactive 4-AMBA analog. Duodenal infusion of the protein hydrolysate increased vagal afferent discharge and inhibited gastric motility; these responses were abolished by concomitant infusion of 4-AMBA, but not 4-APAA. Duodenal infusion with Cefaclor, a substrate of PepT1, increased duodenal vagal afferent activity; Cefaclor and protein hydrolysates selectively activated CCK-responsive vagal afferents. This study demonstrates that products of protein digestion increase spontaneous activity of CCK-sensitive duodenal vagal afferents via a mechanism involving the oligopeptide transporter PepT1.

  9. Excitatory post-synaptic potentials from single muscle spindle afferents in external intercostal motoneurones of the cat.

    PubMed Central

    Kirkwood, P A; Sears, T A

    1982-01-01

    1. The discharges of muscle spindle afferents from the external intercostal muscles of anaesthetized, paralysed cats were recorded from dorsal roots in continuity. The dynamic responses, regularities of firing and conduction velocities of the afferents were measured and used to characterize the afferents as primary-like or secondary-like. 2. The synchronization of afferent discharges was investigated by the construction of cross-correlation histograms from the simultaneously recorded discharges of pairs of afferents. The discharges of primary-like afferents with high dynamic responses were found to be synchronized within a few msec. The cardiac pulse was a strong contributary factor in this synchronization. 3. Intracellular recordings were made from external intercostal motoneurones, and spike-triggered averaging was used to reveal unitary e.p.s.p.s evoked by muscle spindle afferents which were from the same spinal cord segment. Dorsal roots other than the rootlet containing the afferent were cut to prevent the synchronization of afferent discharges from affecting the averaged e.p.s.p.s. 4. For primary-like afferents the mean amplitude of the e.p.s.p.s was 171 microV and the mean connectivity (the proportion of motoneurones connected by one afferent) was between 42 and 48%. 5. The amplitudes and shapes of the e.p.s.p.s varied with the respiratory phase, usually being larger in inspiration than in expiration and sometimes also having a longer time course. In particular some e.p.s.p.s showed that components, only represent in inspiration, which were interpreted as indicating polysynaptic connexions gated by the respiratory cycle. 6. The results are discussed in comparison with the connexions of individual muscle spindle afferents from other muscles, with particular reference to the conduction velocities of the afferents. PMID:6461757

  10. Raphe magnus and reticulospinal actions on primary afferent depolarization of group I muscle afferents in the cat.

    PubMed Central

    Quevedo, J; Eguibar, J R; Jiménez, I; Rudomin, P

    1995-01-01

    1. In the anaesthetized cat, electrical stimulation of the bulbar reticular formation produced a short latency (2.1 +/- 0.3 ms) positive potential in the cord dorsum. In contrast, stimulation of the nucleus raphe magnus with strengths below 50 microA evoked a slow negative potential with a mean latency of 5.5 +/- 0.6 ms that persisted after sectioning the contralateral pyramid and was abolished by sectioning the ipsilateral dorsolateral funiculus. 2. The field potentials evoked by stimulation of the bulbar reticular formation and of the nucleus raphe magnus had a different intraspinal distribution, suggesting activation of different sets of segmental interneurones. 3. Stimulation of these two supraspinal nuclei produced primary afferent depolarization (PAD) in single Ib fibres and inhibited the PAD elicited by group I volleys in single Ia fibres. The inhibition of the PAD of Ia fibres produced by reticulospinal and raphespinal inputs appears to be exerted on different interneurones along the PAD pathway. 4. It is concluded that, although reticulospinal and raphespinal pathways have similar inhibitory effects on PAD of Ia fibres, and similar excitatory effects on the PAD of Ib fibres, their actions are conveyed by partly independent pathways. This would allow their separate involvement in the control of posture and movement. Images Figure 6 PMID:7738852

  11. Raphe magnus and reticulospinal actions on primary afferent depolarization of group I muscle afferents in the cat.

    PubMed

    Quevedo, J; Eguibar, J R; Jiménez, I; Rudomin, P

    1995-02-01

    1. In the anaesthetized cat, electrical stimulation of the bulbar reticular formation produced a short latency (2.1 +/- 0.3 ms) positive potential in the cord dorsum. In contrast, stimulation of the nucleus raphe magnus with strengths below 50 microA evoked a slow negative potential with a mean latency of 5.5 +/- 0.6 ms that persisted after sectioning the contralateral pyramid and was abolished by sectioning the ipsilateral dorsolateral funiculus. 2. The field potentials evoked by stimulation of the bulbar reticular formation and of the nucleus raphe magnus had a different intraspinal distribution, suggesting activation of different sets of segmental interneurones. 3. Stimulation of these two supraspinal nuclei produced primary afferent depolarization (PAD) in single Ib fibres and inhibited the PAD elicited by group I volleys in single Ia fibres. The inhibition of the PAD of Ia fibres produced by reticulospinal and raphespinal inputs appears to be exerted on different interneurones along the PAD pathway. 4. It is concluded that, although reticulospinal and raphespinal pathways have similar inhibitory effects on PAD of Ia fibres, and similar excitatory effects on the PAD of Ib fibres, their actions are conveyed by partly independent pathways. This would allow their separate involvement in the control of posture and movement.

  12. AAS 227: Day 2

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 2 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Plenary Session: Black Hole Physics with the Event Horizon Telescope (by Susanna Kohler)If anyone needed motivation to wake up early this morning, they got it in the form of Feryal Ozel (University of Arizona) enthralling us all with exciting pictures, videos, and words about black holes and the Event Horizon Telescope. Ozel spoke to a packed room (at 8:30am!) about where the project currently stands, and where its heading in the future.The EHT has pretty much the coolest goal ever: actually image the event horizons of black holes in our universe. The problem is that the largest black hole we can look at (Sgr A*, in the center of our galaxy) has an event horizon size of 50 as. For this kind of resolution roughly equivalent to trying to image a DVD on the Moon! wed need an Earth-sized telescope. EHT has solved this problem by linking telescopes around the world, creating one giant, mm-wavelength effective telescope with a baseline the size of Earth.Besides producing awesome images, the EHT will be able to test properties of black-hole spacetime, the no-hair theorem, and general relativity (GR) in new regimes.Ozel walked us through some of the theory prep work we need to do now in order to get the most science out of the EHT, including devising new

  13. AAS 227: Day 1

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or at astrobites.com, or catch ourlive-tweeted updates from the @astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto have so many people tell us that they already know about and useastrobites, and we were excited to introduce a new cohort of students at AAS to astrobites for the first time.Tuesday morning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended today.Opening Address (by Becky Smethurst)The President of the AAS, aka our fearless leader Meg Urry kicked off the meeting this morning at the purely coffee powered hour of 8am this morning. She spoke about the importance of young astronomers at the meeting (heres looking at you reader!) and also the importance of the new Working Group for Accessibility and Disabilities (aka WGAD pronounced like wicked) at the AAS. The Society has made extra effort this year to make the conference accessible to all,a message which was very well received by everyone in attendance.Kavli Lecture: New Horizons Alan Stern (by Becky Smethurst)We were definitely spoilt with the first Plenary lecture at this years conference Alan Stern gave us a a review of the New Horizons mission of the Pluto Fly By (astrobites covered the mission back in July with this post). We were treated to beautiful images, wonderful results and a foray into geology.Before (Hubble) and after #NewHorizons. #thatisall #science #astro alanstern #aas227 pic.twitter.com/kkMt6RsSIR Science News (@topsciencething) January 5, 2016Some awesome facts from the lecture that blew my mind:New Horizons is now 2AU (!) beyond Pluto

  14. Segmental and supraspinal control of synaptic effectiveness of functionally identified muscle afferents in the cat.

    PubMed

    Enríquez, M; Jiménez, I; Rudomin, P

    1996-01-01

    The present investigation documents the patterns of primary afferent depolarization (PAD) of single, functionally identified muscle afferents from the medial gastrocnemius nerve in the intact, anesthetized cat. Classification of the impaled muscle afferents as from muscle spindles or from tendon organs was made according to several criteria, which comprised measurement of conduction velocity and electrical threshold of the peripheral axons, and the maximal frequency followed by the afferent fibers during vibration, as well as the changes in discharge frequency during longitudinal stretch, the projection of the afferent fiber to the motor pool, and, in unparalyzed preparations, the changes in afferent activity during a muscle twitch. In confirmation of a previous study, we found that most muscle spindle afferents (46.1-66.6%, depending on the combination of criteria utilized for receptor classification) had a type A PAD pattern. That is, they were depolarized by stimulation of group I fibers of the posterior biceps and semitendinosus (PBSt) nerve, but not by stimulation of cutaneous nerves (sural and superficial peroneus) or the bulbar reticular formation (RF), which in many cases inhibited the PBSt-induced PAD. In addition, we found a significant fraction of muscle spindle primaries that were depolarized by stimulation of group I PBSt fibers and also by stimulation of the bulbar RF. Stimulation of cutaneous nerves produced PAD in 9.1-31.2% of these fibers (type B PAD pattern) and no PAD in 8.2-15.4% (type C PAD pattern). In contrast to muscle spindle afferents, only the 7.7-15.4% of fibers from tendon organs had a type A PAD pattern, 23-46.1% had a type B and 50-61.5% a type C PAD pattern. These observations suggest that the neuronal circuitry involved in the control of the synaptic effectiveness of muscle spindles and tendon organs is subjected to excitatory as well as to inhibitory influences from cutaneous and reticulospinal fibers. As shown in the accompanying

  15. Discharges in human muscle spindle afferents during a key-pressing task.

    PubMed

    Dimitriou, Michael; Edin, Benoni B

    2008-11-15

    Most manual tasks demand a delicate control of the wrist. Sensory information for this control, e.g. about the position and movement velocity of the hand, is assumed to be primarily provided by muscle spindle afferents. It is known that human muscle spindles in relaxed muscles behave as stretch receptors but it is unclear how they discharge during 'natural' hand movements, since their discharges can also be affected by extrafusal contractions and fusimotor activity. We therefore let subjects perform a centre-out-centre key-pressing task on buttons laid out in a 3 x 3 pattern, a task that allowed unconstrained hand and finger movements and required precise control of the wrist. Microneurography recordings from muscle spindle afferents of the wrist extensor muscles were obtained along with wrist kinematics and electromyographic signals. The discharge rates of afferents were more phase advanced than expected on the length of the radial wrist extensor, which acted as an anti-gravity muscle in the key-pressing task. As such, both acceleration and velocity had significant impacts on the discharge rate of primary afferents, velocity on that of secondary afferents, and length had no impact on either afferent type. The response patterns were different for the two types of muscle spindle afferents from the predominantly eccentrically contracting ulnar wrist extensor: muscle length and velocity had significant impacts on the ensemble response of secondary afferents whereas the primary afferents showed highly variable responses. Accordingly, good predictions of the radial ulnar angular velocity were possible from spindle ensemble responses (R(2) = 0.85) whereas length could be predicted only for phases with lengthening of the ulnar wrist extensor. There are several possible explanations for the unexpectedly large phase advance of spindle afferents in the radial wrist extensor. Given the compliance of tendons, for instance, the phase relationship between the muscle fascicle

  16. The action of knee joint afferents and the concomitant influence of cutaneous (sural) afferents on the discharge of triceps surae gamma-motoneurones in the cat.

    PubMed

    Ellaway, P H; Davey, N J; Ferrell, W R; Baxendale, R H

    1996-01-01

    Electrical stimulation of group II joint afferents of the posterior articular nerve (PAN) to the knee evoked short-latency facilitation and/or inhibition of the background discharge of gastrocnemius-soleus (GS) gamma-motoneurones in decerebrated spinal cats. The latencies of these responses were consistent with mediation via segmental oligosynaptic spinal pathways. In addition, a longer-latency facilitation was frequently observed. Mechanical non-noxious stimulation of the skin within the field of innervation of the sural nerve, on the lateral aspect of the heel, suppressed the short-latency facilitation, but not the inhibition or long-latency facilitation. Brief mechanical indentation of the posterior aspect of the knee joint capsule could elicit facilitation or inhibition of gamma-motoneurones. Facilitation, but not inhibition, was blocked by anaesthesia or section of the PAN. Both actions could be suppressed by mechanical stimulation of the heel. We conclude that GS gamma-motoneurones receive both facilitatory and inhibitory segmental inputs from group II articular afferents arising in the knee joint. Cutaneous afferents from the sural field exert a selective inhibitory influence over the facilitation of fusimotor discharge by articular afferents.

  17. Targeting primary afferent nerves for novel antitussive therapy.

    PubMed

    Undem, Bradley J; Carr, Michael J

    2010-01-01

    The best available data support the hypothesis that there are at least two types of vagal nerves responsible for initiating coughing reflexes. One type of nerve conducts action potentials in the A-range and is characterized by rapidly adapting responses to mechanical probing or acidification of the large airway epithelium. Stimulation of these nerves can evoke cough in unconscious experimental animals and humans. These nerves are important in immediate cough evoked by aspiration and as such perform a critical role in airway defense. The other type of primary afferent nerve involved in cough is the vagal C-fiber. Inhalation of selective C-fiber stimulants leads to cough only in conscious animals. In clinical studies, inhalation of a low concentration of a C-fiber stimulant causes an irritating, itchy urge-to-cough sensation that mimics the urge-to-cough sensations associated with respiratory tract infection, post-infection, gastroesophageal reflux disorders, and inflammatory airway diseases. Here we discuss the recent advances in sensory neurobiology that allow for the targeting of vagal C-fibers for novel antitussive therapy. No attempts are made to be all-inclusive with respect to the numerous possible molecular targets being considered to accomplish this goal. Rather, two general strategies are discussed: decreasing generator potential amplitude and decreasing the efficiency by which a generator potential evokes action-potential discharge. For the first category we focus on two targets, transient receptor potential vanilloid 1 and transient receptor potential A1. For the latter category we focus on recent advances in voltage-gated sodium (Na(V)) channel biology.

  18. Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents.

    PubMed

    Kelamangalath, Lakshmi; Tang, Xiaoqing; Bezik, Kathleen; Sterling, Noelle; Son, Young-Jin; Smith, George M

    2015-09-01

    Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP(+)) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4(+) non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFRα3, which only promoted mistargeted regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Objective characterization of the relative afferent pupillary defect in MS.

    PubMed

    Blazek, Paul; Davis, Scott L; Greenberg, Benjamin M; Conger, Amy; Conger, Darrel; Vernino, Steven; Beh, Shin; Stuve, Olaf; Saidha, Shiv; Ratchford, John N; Green, Ari; Calabresi, Peter A; Balcer, Laura J; Frohman, Teresa C; Frohman, Elliot M

    2012-12-15

    To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS. Binocular infrared pupillometry was performed in 40 control subjects and 32 MS patients with RAPDs, using two precisely defined sequences of alternating light flashes (right-left and left-right). We analyzed three distinct pupillary metrics in response to light stimulation. These included percent diameter change (DC), constriction curve area (CCA), which measures change in diameter over time, and the phase-plane curve area (PCA) which measures change in diameter with change in velocity. Direct and consensual response ratios (for each eye) were computed and analyzed for each metric in response to both the first flash (i.e. first phase) and second flash (i.e. second phase) of the 'swinging flashlight' test. Second flash pupillary response metric asymmetry ratios yielded the highest discriminatory power for RAPD detection. Receiver operating characteristic areas under the curve for each of the pupillary metric response asymmetry ratios were as follows: diameter change: 0.97; constriction curve area: 0.96; phase-plane curve area: 0.95 (p<0.0001 for all comparisons compared to normal subjects). The sum of these three squared ratios (SSR) yielded a combined metric with the greatest discriminatory power (receiver operator characteristic area under the curve=0.99). Second flash (i.e. the second phase of the swinging light test) pupillary metric response asymmetry ratios are highly sensitive and specific for the confirmation and characterization of an RAPD in patients with MS. This objective neurophysiologic method may be useful for studying the relationship between a stereotyped reflex, and nervous system architecture, with potential ramifications for detecting and monitoring neuroprotective and restorative effects of novel agents in MS treatment trials. Copyright © 2012 Elsevier B

  20. Cardiopulmonary sympathetic afferent input to lower thoracic spinal neurons.

    PubMed

    Ammons, W S

    1990-10-08

    Spinal neuronal responses to stimulation of cardiopulmonary sympathetic afferent (CPS) fibers were studied in 25 alpha-chloralose-anesthetized cats. Eighty-two neurons located in the T7-T9 segments were tested for responses to electrical stimulation of CPS fibers. Activity of 55 neurons was altered; 37 were excited, 10 were inhibited, and 8 were both excited and inhibited. All 55 cells with CPS input also responded to stimulation of somatic receptors and the left greater splanchnic nerve (SPL). Somatic receptive fields were primarily located on the upper portion of the abdomen and left lower rib cage. Short and long latency responses occurred following CPS and SPL stimulation. Latencies of responses to CPS stimulation were significantly longer than latencies of responses to SPL stimulation (P less than 0.05). Early responses to CPS stimulation were significantly less in magnitude compared to early responses to SPL stimulation (P less than 0.05). Cell responses to CPS stimulation were reduced in magnitude for as long as 300 ms when a conditioning stimulus was applied to SPL. Inhibitory responses of 10 cells to CPS fiber stimulation were best observed during repetitive stimulation. Eight of the cells were also inhibited by repetitive stimulation of SPL. Injection of bradykinin (4 micrograms/kg) into the left atrium increased activity of 16/30 cells from 8 +/- 2 to 22 +/- 5 spikes/s. The results demonstrate that CPS fiber stimulation alters activity of lower thoracic spinal neurons but not as intensely as SPL stimulation. These neurons may participate in cardiac-abdominal visceral reflexes or the pain of cardiac origin that is referred to the abdomen.

  1. NEUROTROPHIN SELECTIVITY IN ORGANIZING TOPOGRAPHIC REGENERATION OF NOCICEPTIVE AFFERENTS

    PubMed Central

    Kelamangalath, Lakshmi; Tang, Xiaoqing; Bezik, Kathleen; Sterling, Noelle; Son, Young-Jin; Smith, George M.

    2015-01-01

    Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP+) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4+ non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFR-α3, which only promoted mistargeted regeneration. PMID:26054884

  2. Effects of periodontal afferent inputs on corticomotor excitability in humans.

    PubMed

    Zhang, Y; Boudreau, S; Wang, M; Wang, K; Sessle, B; Arendt-Nielsen, L; Svensson, P

    2010-01-01

    The aim of the present study was to determine in humans whether local anaesthesia (LA) or nociceptive stimulation of the periodontal ligaments affects the excitability of the face primary motor cortex (MI) related to the tongue and jaw muscles, as measured by transcranial magnetic stimulation (TMS). Twelve healthy volunteers (11 men, 1 woman, 25.3 +/- 4.2 years) participated in two 3-h sessions separated by 7 days. The LA carbocain or the nociceptive irritant capsaicin was randomly injected into the periodontal ligament of the lower right central incisor. In both sessions, TMS-motor evoked potential (MEP) stimulus-response curves and corticomotor maps were acquired for the tongue and masseter muscles before (baseline) and at 5, 30 and 60 min post-application of carbocain or capsaicin. Transcranial magnetic stimulation-MEP stimulus-response curves were also acquired at these time points for the first dorsal interosseous (FDI) as an internal control. Burning pain intensity and mechanical sensitivity ratings to a von Frey filament applied to the application site were recorded on an electronic visual analogue scale (VAS). All subjects reported a decreased mechanical sensitivity (anova: P = 0.004) in the LA session and a burning pain sensation (VAS peak pain: 6.4 +/- 1.0) in the capsaicin session. No significant changes in cortical excitability of the MI, as reflected by TMS-MEP stimulus-response curves or corticomotor maps for the tongue, masseter or FDI were found between baseline and post-injection for the LA (anovas: P > 0.22) or capsaicin (anovas: P > 0.16) sessions. These findings suggest that a transient loss or perturbation in periodontal afferent input to the brain from a single incisor is insufficient to cause changes in corticomotor excitability of the face MI, as measured by TMS in humans.

  3. Piezo2 Expression in Mechanosensitive Dental Primary Afferent Neurons.

    PubMed

    Won, J; Vang, H; Lee, P R; Kim, Y H; Kim, H W; Kang, Y; Oh, S B

    2017-07-01

    Mechanosensitive ion channels have been suggested to be expressed in dental primary afferent (DPA) neurons to transduce the movement of dentinal fluid since the proposal of hydrodynamic theory. Piezo2, a mechanosensitive, rapidly inactivating (RI) ion channel, has been recently identified in dorsal root ganglion (DRG) neurons to mediate tactile transduction. Here, we examined the expression of Piezo2 in DPA neurons by in situ hybridization, single-cell reverse transcriptase polymerase chain reaction, and whole-cell patch-clamp recordings. DPA neurons with Piezo2 messenger RNA (mRNA) or Piezo2-like currents were further characterized based on their neurochemical and electrophysiological properties. Piezo2 mRNA was found mostly in medium- to large-sized DPA neurons, with the majority of these neurons also positive for Nav1.8, CGRP, and NF200, whereas only a minor population was positive for IB4 and peripherin. Whole-cell patch-clamp recordings revealed Piezo2-like, RI currents evoked by mechanical stimulation in a subpopulation of DPA neurons. RI currents were pharmacologically blocked by ruthenium red, a compound known to block Piezo2, and were also reduced by small interfering RNA-mediated Piezo2 knockdown. Piezo2-like currents were observed almost exclusively in IB4-negative DPA neurons, with the current amplitude larger in capsaicin-insensitive DPA neurons than the capsaicin-sensitive population. Our findings show that subpopulation of DPA neurons is indeed mechanically sensitive. Within this subpopulation of mechanosensitive DPA neurons, we have identified the Piezo2 ion channel as a potential transducer for mechanical stimuli, contributing to RI inward currents. Piezo2-positive DPA neurons were characterized as medium- to large-sized neurons with myelinated A-fibers, containing nociceptive peptidergic neurotransmitters.

  4. Differential modulation of primary afferent depolarization of segmental and ascending intraspinal collaterals of single muscle afferents in the cat spinal cord.

    PubMed

    Rudomin, P; Lomelí, J; Quevedo, J

    2004-06-01

    We examined primary afferent depolarization (PAD) in the anesthetized cat elicited in 109 pairs of intraspinal collaterals of single group I afferents from the gastrocnemius nerve, one of the pair ending in the L3 segment, around the Clarke's column nuclei, and the other in the L6 segment within the intermediate zone. Tests for refractoriness were made to assess whether the responses produced by intraspinal stimulation in the L3 and L6 segments were due to activation of collaterals of the same afferent fiber. PAD in each collateral was estimated by independent computer-controlled measurement of the intraspinal current required to maintain a constant probability of antidromic firing. In most fibers, stimulation of the ipsilateral posterior biceps and semitendinosus (PBSt) nerve with trains of pulses maximal for group I afferents had a qualitatively similar effect but produced a larger PAD in the L6 than in the L3 collaterals. Stimulation of cutaneous nerves (sural and superficial peroneus) with single pulses and of the posterior articular nerve, the ipsilateral reticular formation, nucleus raphe magnus and contralateral motor cortex with trains of pulses often had qualitatively different effects. They could produce PAD and/or facilitate the PBSt-induced PAD in one collateral, and produce PAH and/or inhibit the PAD in the other collateral. These patterns could be changed in a differential manner by sensory or supraspinal conditioning stimulation. In summary, the present investigation suggests that the segmental and ascending collaterals of individual afferents are not fixed routes for information transmission, but parts of dynamic systems in which information transmitted to segmental reflex pathways and to Clarke's column neurons by common sources can be decoupled by sensory and descending inputs and funneled to specific targets according to the motor tasks to be performed.

  5. Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

    PubMed Central

    Chagas, André M.; Theis, Lucas; Sengupta, Biswa; Stüttgen, Maik C.; Bethge, Matthias; Schwarz, Cornelius

    2013-01-01

    Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of “how much” information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on “what” is coded by primary afferents. Amongst the kinematic variables tested—position, velocity, and acceleration—primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80–90%. The final 10–20% were found to be due to non-linear coding by spike bursts. PMID:24367295

  6. Genetic Tracing of Nav1.8-Expressing Vagal Afferents in the Mouse

    PubMed Central

    Gautron, Laurent; Sakata, Ichiro; Udit, Swalpa; Zigman, Jeffrey M.; Wood, John N.; Elmquist, Joel K.

    2012-01-01

    Nav1.8 is a tetrodotoxin-resistant sodium channel present in large subsets of peripheral sensory neurons, including both spinal and vagal afferents. In spinal afferents, Nav1.8 plays a key role in signaling different types of pain. Little is known, however, about the exact identity and role of Nav1.8-expressing vagal neurons. Here we generated mice with restricted expression of tdTomato fluorescent protein in all Nav1.8-expressing afferent neurons. As a result, intense fluorescence was visible in the cell bodies, central relays, and sensory endings of these neurons, revealing the full extent of their innervation sites in thoracic and abdominal viscera. For instance, vagal and spinal Nav1.8-expressing endings were seen clearly within the gastrointestinal mucosa and myenteric plexus, respectively. In the gastrointestinal muscle wall, labeled endings included a small subset of vagal tension receptors but not any stretch receptors. We also examined the detailed inner-vation of key metabolic tissues such as liver and pancreas and evaluated the anatomical relationship of Nav1.8-expressing vagal afferents with select enteroendocrine cells (i.e., ghrelin, glucagon, GLP-1). Specifically, our data revealed the presence of Nav1.8-expressing vagal afferents in several metabolic tissues and varying degrees of proximity between Nav1.8-expressing mucosal afferents and enteroendocrine cells, including apparent neuroendocrine apposition. In summary, this study demonstrates the power and versatility of the Cre-LoxP technology to trace identified visceral afferents, and our data suggest a previously unrecognized role for Nav1.8-expressing vagal neurons in gastrointestinal functions. PMID:21618224

  7. Comparison of baroreceptive to other afferent synaptic transmission to the medial solitary tract nucleus.

    PubMed

    Andresen, Michael C; Peters, James H

    2008-11-01

    Cranial nerve visceral afferents enter the brain stem to synapse on neurons within the solitary tract nucleus (NTS). The broad heterogeneity of both visceral afferents and NTS neurons makes understanding afferent synaptic transmission particularly challenging. To study a specific subgroup of second-order neurons in medial NTS, we anterogradely labeled arterial baroreceptor afferents of the aortic depressor nerve (ADN) with lipophilic fluorescent tracer (i.e., ADN+) and measured synaptic responses to solitary tract (ST) activation recorded from dye-identified neurons in medial NTS in horizontal brain stem slices. Every ADN+ NTS neuron received constant-latency ST-evoked excitatory postsynaptic currents (EPSCs) (jitter < 192 micros, SD of latency). Stimulus-recruitment profiles showed single thresholds and no suprathreshold recruitment, findings consistent with EPSCs arising from a single, branched afferent axon. Frequency-dependent depression of ADN+ EPSCs averaged approximately 70% for five shocks at 50 Hz, but single-shock failure rates did not exceed 4%. Whether adjacent ADN- or those from unlabeled animals, other second-order NTS neurons (jitters < 200 micros) had ST transmission properties indistinguishable from ADN+. Capsaicin (CAP; 100 nM) blocked ST transmission in some neurons. CAP-sensitive ST-EPSCs were smaller and failed over five times more frequently than CAP-resistant responses, whether ADN+ or from unlabeled animals. Variance-mean analysis of ST-EPSCs suggested uniformly high probabilities for quantal glutamate release across second-order neurons. While amplitude differences may reflect different numbers of contacts, higher frequency-dependent failure rates in CAP-sensitive ST-EPSCs may arise from subtype-specific differences in afferent axon properties. Thus afferent transmission within medial NTS differed by axon class (e.g., CAP sensitive) but was indistinguishable by source of axon (e.g., baroreceptor vs. nonbaroreceptor).

  8. The unsilent majority-TRPV1 drives "spontaneous" transmission of unmyelinated primary afferents within cardiorespiratory NTS.

    PubMed

    Andresen, Michael C; Hofmann, Mackenzie E; Fawley, Jessica A

    2012-12-15

    Cranial primary afferent sensory neurons figure importantly in homeostatic control of visceral organ systems. Of the two broad classes of visceral afferents, the role of unmyelinated or C-type class remains poorly understood. This review contrasts key aspects of peripheral discharge properties of C-fiber afferents and their glutamate transmission mechanisms within the solitary tract nucleus (NTS). During normal prevailing conditions, most information arrives at the NTS through myelinated A-type nerves. However, most of visceral afferent axons (75-90%) in NTS are unmyelinated, C-type axons. Centrally, C-type solitary tract (ST) afferent terminals have presynaptic transient receptor potential vanilloid type 1 (TRPV1) receptors. Capsaicin activation of TRPV1 blocks phasic or synchronous release of glutamate but facilitates release of glutamate from a separate pool of vesicles. This TRPV1-operated pool of vesicles is active at normal temperatures and is responsible for actively driving a 10-fold higher release of glutamate at TRPV1 compared with TRPV1- terminals even in the absence of afferent action potentials. This novel TRPV1 mechanism is responsible for an additional asynchronous release of glutamate that is not present in myelinated terminals. The NTS is rich with presynaptic G protein-coupled receptors, and the implications of TRPV1-operated glutamate offer unique targets for signaling in C-type sensory afferent terminals from neuropeptides, inflammatory mediators, lipid metabolites, cytokines, and cannabinoids. From a homeostatic view, this combination could have broad implications for integration in chronic pathological disturbances in which the numeric dominance of C-type endings and TRPV1 would broadly disturb multisystem control mechanisms.

  9. A novel preparation to study rat pancreatic spinal and vagal mechanosensitive afferents in vitro.

    PubMed

    Schloithe, A C; Sutherland, K; Woods, C M; Blackshaw, L A; Davison, J S; Toouli, J; Saccone, G T P

    2008-09-01

    The management of pancreatic pain is a significant clinical problem so understanding of how sensory signals are generated in pancreatic tissue is fundamental. We aimed to characterize mechanosensitive and chemosensitive properties of pancreatic spinal and vagal afferents in vitro. Spinal and vagal afferent preparations from Sprague-Dawley rats were established incorporating the left splanchnic nerve or vagus nerves respectively. The common bile duct was cannulated for distension of the pancreatic duct with fluid. Nerve discharge evoked by blunt probing, duct distension or electrical stimulation was obtained from teased nerve bundles using standard extra-cellular recording. Discharge from 197 spinal afferent bundles was recorded, of which 57% displayed spontaneous activity. Blunt probing revealed 61 mechanosensitive receptive fields which were associated primarily with arteries/blood vessels (33/61) and the parenchyma (22/61). All mechanosensitive responses were slowly adapting, with 33% continuing to discharge after termination of the stimulus and 60% displaying a response threshold <10 g. Application of chemical mediators (bradykinin, histamine, 5-hydroxytryptamine, cholecystokinin octapeptide) evoked a response from 31/57 units, with 33% excitatory and 23% inhibitory. Spontaneous discharge was recorded from 72% of 135 vagal bundles. Mechanosensitive receptive fields were not identified in the pancreas but were evident in adjacent organs. No spinal or vagal afferent response to duct distension was obtained. In conclusion, pancreatic mechanosensitive spinal afferents are common, in contrast to pancreatic mechanosensitive vagal afferents indicating that pancreatic sensory innervation is predominantly spinal. Chemosensitive spinal afferent nerve endings are present in the pancreas and respond to a variety of inflammatory and physiological mediators.

  10. Spinal projection of spindle afferents of the longissimus lumborum muscles of the cat.

    PubMed

    Durbaba, R; Taylor, A; Ellaway, P H; Rawlinson, S

    2007-04-15

    The connections and monosynaptic projections of muscle spindle afferents of individual heads of the longissimus lumborum have been studied in cats by natural stimulation, by electrical stimulation and by spike-triggered averaging from single identified afferents. The spindle afferents were classified by sensitivity to vibration and by the effect of succinylcholine on their response to ramp-and-hold muscle stretches. Axonal conduction and synaptic effects were recorded as field potentials and focal synaptic potentials during systematic exploration of the spinal cord in segments L1 to L4 with extracellular metal microelectrodes, singly and in linear arrays. Ascending branches of afferent axons within the cord had a significantly higher mean conduction velocity (CV: 56.5 m s(-1)) than descending branches (40.8 m s(-1)). The CV of ascending branches was significantly positively correlated with a measure of the strength of intrafusal bag(2) muscle fibre contacts, but not to a measure of bag(1) contacts. Two sites of monosynaptic excitatory projection in the cord were identified, namely to the intermediate region (laminae V, VI and VII) and to ventral horn region (laminae VIII and IX). In tests of 154 single afferents, signs of central projection were detected for 60, providing 122 regions of maximum negative focal synaptic potentials (FSPs) of mean amplitude 7.51 microV. Their longitudinal spacing indicated that axons gave off descending collaterals at intervals of 1.5-3.5 mm. Based on the amplitude of FSPs, the projection of secondary afferents is stronger than that of primaries in the intermediate region and possibly also in the ventral horn region. Evidence is also presented that spindle afferent input from different heads of the longissimus converges into any given spinal segment and that input in one spinal root projects to adjacent segments. It is concluded that the organization of the longissimus monosynaptic spindle input favours relatively tonic and diffuse

  11. Potentiation of mouse vagal afferent mechanosensitivity by ionotropic and metabotropic glutamate receptors

    PubMed Central

    Slattery, James A; Page, Amanda J; Dorian, Camilla L; Brierley, Stuart M; Blackshaw, L Ashley

    2006-01-01

    Glutamate acts at central synapses via ionotropic (iGluR – NMDA, AMPA and kainate) and metabotropic glutamate receptors (mGluRs). Group I mGluRs are excitatory whilst group II and III are inhibitory. Inhibitory mGluRs also modulate peripherally the mechanosensitivity of gastro-oesophageal vagal afferents. Here we determined the potential of excitatory GluRs to play an opposing role in modulating vagal afferent mechanosensitivity, and investigated expression of receptor subunit mRNA within the nodose ganglion. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of selective GluR ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors, which respond only to mucosal stroking. The selective iGluR agonists NMDA and AMPA concentration-dependently potentiated afferent responses. Their corresponding antagonists AP-5 and NBQX alone attenuated mechanosensory responses as did the non-selective antagonist kynurenate. The kainate selective agonist SYM-2081 had minor effects on mechanosensitivity, and the antagonist UBP 302 was ineffective. The mGluR5 antagonist MTEP concentration-dependently inhibited mechanosensitivity. Efficacy of agonists and antagonists differed on mucosal and tension receptors. We conclude that excitatory modulation of afferent mechanosensitivity occurs mainly via NMDA, AMPA and mGlu5 receptors, and the role of each differs according to afferent subtypes. PCR data indicated that all NMDA, kainate and AMPA receptor subunits plus mGluR5 are expressed, and are therefore candidates for the neuromodulation we observed. PMID:16945965

  12. Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

    PubMed

    Ro, J Y; Capra, N F

    2001-05-01

    Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

  13. Functional expression of α7-nicotinic acetylcholine receptors by muscle afferent neurons

    PubMed Central

    Baxter, James C.; Ramachandra, Renuka; Mayne, Dustin R.

    2014-01-01

    The exercise pressor reflex (EPR) is generated by group III and IV muscle afferents during exercise to increase cardiovascular function. Muscle contraction is triggered by ACh, which is metabolized into choline that could serve as a signal of exercise-induced activity. We demonstrate that ACh can induce current in muscle afferents neurons isolated from male Sprague-Dawley rats. The nicotinic ACh receptors (nAChRs) appear to be expressed by some group III-IV neurons since capsaicin (TRPV1) and/or ATP (P2X) induced current in 56% of ACh-responsive neurons. α7- And α4β2-nAChRs have been shown to be expressed in sensory neurons. An α7-nAChR antibody stained 83% of muscle afferent neurons. Functional expression was demonstrated by using the specific α7-nAChR blockers α-conotoxin ImI (IMI) and methyllycaconitine (MLA). MLA inhibited ACh responses in 100% of muscle afferent neurons, whereas IMI inhibited ACh responses in 54% of neurons. Dihydro-β-erythroidine, an α4β2-nAChR blocker, inhibited ACh responses in 50% of muscle afferent neurons, but recovery from block was not observed. Choline, an α7-nAChR agonist, elicited a response in 60% of ACh-responsive neurons. Finally, we demonstrated the expression of α7-nAChR by peripherin labeled (group IV) afferent fibers within gastrocnemius muscles. Some of these α7-nAChR-positive fibers were also positive for P2X3 receptors. Thus choline could serve as an activator of the EPR by opening α7-nAChR expressed by group IV (and possible group III) afferents. nAChRs could become pharmacological targets for suppressing the excessive EPR activation in patients with peripheral vascular disease. PMID:24966300

  14. AAS 227: Day 3

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 3 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Henry Norris Russell Lecture: Viewing the Universe with Infrared Eyes: The Spitzer Space Telescope (by Erika Nesvold)The Henry Norris Russell Award is the highest honor given by the AAS, for a lifetime of eminence in astronomy research. This years award went to Giovanni Fazio of the Harvard-Smithsonian Center for Astrophysics. Fazio became a leader in gamma ray astronomy before switching mid-career to the study of infrared astronomy, and he gave his award lecture on the latter subject, specifically on the Spitzer Space Telescope, one of the most successful infrared telescopes of all time.Artists rendering of the Spitzer space telescope. [NASA/JPL-Caltech]Spitzer has been operating for more than twelve years, and has resulted in over six thousand papers in refereed journals in that time. The telescope sits in an Earth-trailing orbit around the Sun, and is now farther from the Earth (1.4 AU) than the Earth is from the Sun. Fazio gave the audience a fascinating overview of the science done by Spitzer over more than a decade. One of the most productive areas of research for Spitzer is the study of exoplanets, which hadnt even been discovered when the Spitzer Telescope was first conceived. Spitzers high sensitivity and ability to observe exoplanets over

  15. Tonic and phasic differential GABAergic inhibition of synaptic actions of joint afferents in the cat.

    PubMed

    Rudomin, P; Hernández, E; Lomelí, J

    2007-01-01

    The aim of this study was to examine the functional organization of the spinal neuronal networks activated by myelinated afferent fibers in the posterior articular nerve (PAN) of the anesthetized cat. Particular attention was given to the tonic and phasic GABAa inhibitory modulation of these networks. Changes in the synaptic effectiveness of the joint afferents were inferred from changes in the intraspinal focal potentials produced by electrical stimulation of the PAN. We found that conditioning stimulation of cutaneous nerves (sural, superficial peroneus and saphenous) and of the nucleus raphe magnus often inhibited, in a differential manner, the early and late components of the intraspinal focal potentials produced by stimulation of low and high threshold myelinated PAN afferents, respectively. The degree of the inhibition depended on the strength of both the conditioning and test stimuli and on the segmental level of recording. Conditioning stimulation of group I muscle afferents was less effective, but marked depression of the early and late focal potentials was produced by stimuli exceeding 5 xT. The i.v. injection of 1-2.5 mg/kg of picrotoxin, a GABAa blocker, had relatively minor effects on the early components of the PAN focal potentials, but was able to induce a significant increase of the late components. It also reduced the inhibitory effects of cutaneous and joint nerve conditioning on PAN focal responses. Conditioning autogenetic stimulation with high-frequency trains depressed the PAN focal potentials. The late components of the PAN responses remained depressed several minutes after discontinuing the conditioning train, even after picrotoxin administration. The present observations indicate that the neuronal networks activated by the low threshold PAN afferents show a relatively small post-activation depression and appear to be subjected to a minor tonic inhibitory GABAa control. In contrast, the pathways activated by stimulation of high threshold

  16. Purinergic signalling underlies transforming growth factor‐β‐mediated bladder afferent nerve hyperexcitability

    PubMed Central

    Gonzalez, Eric J.; Heppner, Thomas J.; Nelson, Mark T.

    2016-01-01

    Key points The sensory components of the urinary bladder are responsible for the transduction of bladder filling and are often impaired with neurological injury or disease.Elevated extracellular ATP contributes, in part, to bladder afferent nerve hyperexcitability during urinary bladder inflammation or irritation.Transforming growth factor‐β1 (TGF‐β1) may stimulate ATP release from the urothelium through vesicular exocytosis mechanisms with minimal contribution from pannexin‐1 channels to increase bladder afferent nerve discharge.Bladder afferent nerve hyperexcitability and urothelial ATP release with CYP‐induced cystitis is decreased with TGF‐β inhibition.These results establish a causal link between an inflammatory mediator, TGF‐β, and intrinsic signalling mechanisms of the urothelium that may contribute to the altered sensory processing of bladder filling. Abstract The afferent limb of the micturition reflex is often compromised following bladder injury, disease and inflammatory conditions. We have previously demonstrated that transforming growth factor‐β (TGF‐β) signalling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Despite the functional presence of TGF‐β in bladder inflammation, the precise mechanisms of TGF‐β mediating bladder dysfunction are not yet known. Thus, the present studies investigated the sensory components of the urinary bladder that may underlie the pathophysiology of aberrant TGF‐β activation. We utilized bladder–pelvic nerve preparations to characterize bladder afferent nerve discharge and the mechanisms of urothelial ATP release with distention. Our findings indicate that bladder afferent nerve discharge is sensitive to elevated extracellular ATP during pathological conditions of urinary bladder inflammation or irritation. We determined that TGF‐β1 may increase bladder afferent nerve excitability by stimulating ATP release from the urothelium via vesicular

  17. The role of corneal afferent neurons in regulating tears under normal and dry eye conditions.

    PubMed

    Meng, Ian D; Kurose, Masayuki

    2013-12-01

    The cornea is one of several orofacial structures requiring glandular secretion for proper lubrication. Glandular secretion is regulated through a neural reflex initiated by trigeminal primary afferent neurons innervating the corneal epithelium. Corneal sensory afferents must respond to irritating and potentially damaging stimuli, as well as drying that occurs with evaporation of the tear film, and the physiological properties of corneal afferents are consistent with these requirements. Polymodal neurons are sensitive to noxious mechanical, thermal and chemical stimuli, mechanoreceptive neurons are selectively activated by mechanical stimuli, and cool cells respond to innocuous cooling. The central terminations of corneal primary afferents are located within two regions of the spinal trigeminal nucleus. The more rostral region, located at the transition between the trigeminal subnucleus caudalis and interpolaris, represents a critical relay for the regulation of the lacrimation reflex. From this region, major control of lacrimation is carried through projections to preganglionic parasympathetic neurons located in or around the superior salivatory nucleus. Dry eye syndrome may be caused by a dysfunction in the tear secreting glands themselves or in the neuronal circuit regulating these glands. Furthermore, the dry eye condition itself may modify the properties of corneal afferents and affect their ability to regulate secretion, a possibility just now being explored. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The role of corneal afferent neurons in regulating tears under normal and dry eye conditions

    PubMed Central

    Meng, Ian D.; Kurose, Masayuki

    2013-01-01

    The cornea is one of several orofacial structures requiring glandular secretion for proper lubrication. Glandular secretion is regulated through a neural reflex initiated by trigeminal primary afferent neurons innervating the corneal epithelium. Corneal sensory afferents must respond to irritating and potentially damaging stimuli, as well as drying that occurs with evaporation of the tear film, and the physiological properties of corneal afferents are consistent with these requirements. Polymodal neurons are sensitive to noxious mechanical, thermal and chemical stimuli, mechanoreceptive neurons are selectively activated by mechanical stimuli, and cool cells respond to innocuous cooling. The central terminations of corneal primary afferents are located within two regions of the spinal trigeminal nucleus. The more rostral region, located at the transition between the trigeminal subnucleus caudalis and interpolaris, represents a critical relay for the regulation of the lacrimation reflex. From this region, major control of lacrimation is carried through projections to preganglionic parasympathetic neurons located in or around the superior salivatory nucleus. Dry eye syndrome may be caused by a dysfunction in the tear secreting glands themselves or in the neuronal circuit regulating these glands. Furthermore, the dry eye condition itself may modify the properties of corneal afferents and affect their ability to regulate secretion, a possibility just now being explored. PMID:23994439

  19. Inhibition of Repulsive Guidance Molecule, RGMa, Increases Afferent Synapse Formation with Auditory Hair Cells

    PubMed Central

    Brugeaud, Aurore; Tong, Mingjie; Luo, Li; Edge, Albert S.B.

    2017-01-01

    The peripheral fibers that extend from auditory neurons to hair cells are sensitive to damage, and replacement of the fibers and their afferent synapse with hair cells would be of therapeutic interest. Here, we show that RGMa, a repulsive guidance molecule previously shown to play a role in the development of the chick visual system, is expressed in the developing, newborn, and mature mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons and hair cells, from which afferent connections had been removed, was assessed. Contact of neural processes with hair cells and elaboration of postsynaptic densities at sites of the ribbon synapse were increased by treatment with a blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature branching pattern of afferent neurons was accelerated. Inhibition by RGMa could thus explain why auditory neurons have a low capacity to regenerate peripheral processes: postnatal spiral ganglion neurons retain the capacity to send out processes that respond to signals for synapse formation, but expression of RGMa postnatally appears to be detrimental to regeneration of afferent hair cell innervation and antagonizes synaptogenesis. Increased synaptogenesis after inhibition of RGMa suggests that manipulation of guidance or inhibitory factors may provide a route to increase formation of new synapses at deafferented hair cells. PMID:24123853

  20. Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of Rats.

    PubMed

    Kanda, Hirosato; Gu, Jianguo G

    2017-04-25

    Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/μm, and the tension was significantly decreased to ∼29 pN/μm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/μm by methyl-β-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation

    PubMed Central

    Rybak, Ilya A; Stecina, Katinka; Shevtsova, Natalia A; McCrea, David A

    2006-01-01

    A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-centre rhythm generator (RG) and pattern formation (PF) networks has been developed from observations obtained during fictive locomotion in decerebrate cats. Sensory afferents have been incorporated in the model to study the effects of afferent stimulation on locomotor phase switching and step cycle period and on the firing patterns of flexor and extensor motoneurones. Here we show that this CPG structure can be integrated with reflex circuits to reproduce the reorganization of group I reflex pathways occurring during locomotion. During the extensor phase of fictive locomotion, activation of extensor muscle group I afferents increases extensor motoneurone activity and prolongs the extensor phase. This extensor phase prolongation may occur with or without a resetting of the locomotor cycle, which (according to the model) depends on the degree to which sensory input affects the RG and PF circuits, respectively. The same stimulation delivered during flexion produces a temporary resetting to extension without changing the timing of following locomotor cycles. The model reproduces this behaviour by suggesting that this sensory input influences the PF network without affecting the RG. The model also suggests that the different effects of flexor muscle nerve afferent stimulation observed experimentally (phase prolongation versus resetting) result from opposing influences of flexor group I and II afferents on the PF and RG circuits controlling the activity of flexor and extensor motoneurones. The results of modelling provide insights into proprioceptive control of locomotion. PMID:17008375

  2. [Responses of afferent unit of the caudal nerve of diabetic hyperalgesic rats to sympathetic efferent stimulation].

    PubMed

    Liu, J; Wang, K M; Zhang, Q J; Cao, D Y

    2001-12-01

    Responses of afferent unit to sympathetic stimulation (SS), intravenous injection of noradrenaline (NA) and phentolamine in the caudal nerve of diabetic rats were investigated. The results showed that the discharge frequencies of C and Adelta units with spontaneous discharges were increased in diabetic hyperalgesic rats after SS, and these spontaneous discharges were eliminated by adrenergic antagonist. The C (6/21) and Adelta (19/81) units with no spontaneous discharges of diabetic hyperalgesic rat turned from silent state into active state during SS; although SS did not elicit afferent discharges of the C mechanical receptive units (C-M), it elicited afferent discharges of a part of C mechano heat units (C-MH) and C polymodal units (C-Pol); afferent discharges of some of the Adelta mechanical receptive units (Adelta-M) and Adelta mechano heat units (Adelta-MH) were also elicited by SS. The latencies of the C and Adelta units responses upon SS were not equal, but no less than 5 s. SS elicited neither afferent discharges from Abeta mechanical receptive units of diabetic hyperalgesic rat, nor receptive units of all types in the control rat. The C(3/8) and Adelta (4/12) units of diabetic hyperalgesic rat were activated by intravenous injection of NA. The present data suggest that NA released from sympathetic nerve terminals excites C and Adelta units of diabetic hypesthesic rat, which may be a peripheral factor in hyperalgesia and paresthesia of diabetic rats.

  3. Maternal care effects on SNB motoneuron development: the mediating role of sensory afferent distribution and activity.

    PubMed

    Lenz, Kathryn M; Sengelaub, Dale R

    2009-08-01

    Maternal licking in rats affects the development of the spinal nucleus of the bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile reflexes involved with copulation. Reduced maternal licking produces decreased motoneuron number, size, and dendritic length in the rostral portion of the adult SNB as well as deficits in adult male copulatory behavior. Previous research suggests that decreases in perineal tactile stimulation may be responsible for these effects. To determine whether the regional effects of maternal licking on SNB morphology are driven by sensory afferent innervation of the lumbosacral spinal cord, we used WGA-HRP to reconstruct the location of sensory afferent fibers from the perineal skin. We found that these fibers are caudally concentrated relative to the area of the SNB dendritic field, with the rostral dendritic arbor receiving little perineal afferent innervation. We also assessed Fos expression following perineal tactile stimulation to determine whether it increased local spinal cord activity in the SNB dendritic field. Sixty seconds of licking-like perineal stimulation produced a transient 115% increase in Fos expression in the area of the SNB dendritic field. This effect was driven by a significant increase in Fos in the caudal portion of the SNB dendritic field, matching the pattern of perineal afferent fiber labeling. Perineal tactile stimulation also produced significantly greater Fos expression in male pups than in female pups. Together, these results suggest that perineal sensory afferent activity mediates the effects of early maternal care on the masculinization of the SNB and resultant male copulatory behavior.

  4. Vagal innervation of intestines: afferent pathways mapped with new en bloc horseradish peroxidase adaptation.

    PubMed

    Wang, Feng-Bin; Powley, Terry L

    2007-08-01

    Neural tracers have not typically been employed to determine the pathways followed by axons between their perikarya and target tissues. We have adapted the tetramethylbenzidine method for horseradish peroxidase (HRP) to stain fibers en bloc in organs and thus to delineate axonal trajectories. We have also applied this protocol to characterize the pathways that vagal afferents follow to the intestines. The protocol confirms that the proximal segment of the duodenum receives afferents carried in the vagal hepatic branch and demonstrates that vagal afferents innervating the remainder of the small and large intestines course through multiple fascicles derived from the celiac branches of the abdominal vagus. These fascicles divide, intermingle, and reorganize along the abdominal aorta and superior mesenteric artery (SMA), but not along the inferior mesenteric artery, and then project to the intestines with secondary arteries that branch from the SMA. The inferior pancreaticoduodenal, jejunal, middle colic, right colic, and ileocecocolic arteries all carry vagal afferents to segments of the intestines. As the arteries derived from the SMA divide repeatedly into successively finer branches and course to the intestines, the vagal afferent fascicles (typically a pair) running with each arterial branch also divide. These divisions generate sets/pairs of finer fascicles coursing with even the highest order arterial radicles. The vagal fascicles enter the intestinal wall with the vessels and appear to innervate the organ near the point of entry. The results verify the practicality and sensitivity of the en bloc HRP technique and suggest that the protocol could delineate other peripheral pathways.

  5. Afferent fibers involved in the bradykinin-induced cardiovascular reflexes from the ovary in rats.

    PubMed

    Uchida, Sae; Kagitani, Fusako; Hotta, Harumi

    2015-12-01

    Bleeding or rupture of the ovary often accompanies ovarian cysts and causes severe pain and autonomic responses such as hypotension. It would be expected that ovarian afferents contribute to cardiovascular responses induced by ovarian failure. The present study examined cardiovascular responses to noxious chemical stimulation of the ovary by bradykinin, an algesic substance released by tissue damage, and explored the role of ovarian afferents in the ovarian-cardiovascular responses in anesthetized rats. Non-pregnant adult rats were anesthetized with pentobarbital and artificially ventilated. The carotid artery was cannulated to monitor blood pressure and heart rate. Noxious chemical stimulation was achieved by applying a small piece of cotton soaked with bradykinin to the surface of the ovary for 30s. Application of bradykinin (10(-4) M) to the ovary decreased heart rate and blood pressure. These cardiovascular responses were not significantly influenced by severance of the vagal nerves or the superior ovarian nerve, but were abolished by severance of the ovarian nerve plexus (ONP). Application of bradykinin (10(-4) M) to the ovary evoked afferent activity of the ONP both in vivo and in vitro preparations. These results indicate that the decreases in heart rate and blood pressure following chemical noxious stimulation of the ovary with bradykinin are reflex responses, whose afferent nerve pathway is mainly through afferent fibers in the ONP.

  6. Hysteretic behavior of bladder afferent neurons in response to changes in bladder pressure.

    PubMed

    Ross, Shani E; Sperry, Zachariah J; Mahar, Colin M; Bruns, Tim M

    2016-08-12

    Mechanosensitive afferents innervating the bladder increase their firing rate as the bladder fills and pressure rises. However, the relationship between afferent firing rates and intravesical pressure is not a simple linear one. Firing rate responses to pressure can differ depending on prior activity, demonstrating hysteresis in the system. Though this hysteresis has been commented on in published literature, it has not been quantified. Sixty-six bladder afferents recorded from sacral dorsal root ganglia in five alpha-chloralose anesthetized felines were identified based on their characteristic responses to pressure (correlation coefficient ≥ 0.2) during saline infusion (2 ml/min). For saline infusion trials, we calculated a maximum hysteresis ratio between the firing rate difference at each pressure and the overall firing rate range (or Hmax) of 0.86 ± 0.09 (mean ± standard deviation) and mean hysteresis ratio (or Hmean) of 0.52 ± 0.13 (n = 46 afferents). For isovolumetric trials in two experiments (n = 33 afferents) Hmax was 0.72 ± 0.14 and Hmean was 0.40 ± 0.14. A comprehensive state model that integrates these hysteresis parameters to determine the bladder state may improve upon existing neuroprostheses for bladder control.

  7. A role for chloride in the suppressive effect of acetylcholine on afferent vestibular activity.

    PubMed

    Pantoja, A M; Holt, J C; Guth, P S

    1997-10-01

    Afferents of the frog semicircular canal (SCC) respond to acetylcholine (ACh) application (0.3-1.0 mM) with a facilitation of their activity while frog saccular afferents respond with suppression (Guth et al., 1994). All recordings are of resting (i.e., non-stimulated) multiunit activity as previously reported (Guth et al., 1994). Substitution of 80% of external chloride (Cl-) by large, poorly permeant anions of different structures (isethionate, methanesulfonate, methylsulfate, and gluconate) reduced the suppressive effect of ACh in the frog saccular afferents. This substitution did not affect the facilitatory response of SCC afferents to ACh. Chloride channel blockers were also used to test further whether Cl- is involved in the ACh suppressive effect. These included: niflumic and flufenamic acids, picrotoxin, 5-nitro-2-(-3-phenylpropylamino)benzoic acid (NPPB), and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). As with the Cl- substitutions, all of these agents reduced the suppressive response to ACh in the saccule, but not the facilitatory response seen in the SCC. The suppressive effect of ACh on saccular afferents is considered to be due to activation of a nicotinic-like receptor (Guth et al., 1994; Guth and Norris, 1996). Taking into account the effects of both Cl- substitutions and Cl- channel blockers, we conclude that changes in Cl- availability influence the suppressive effect of ACh and that therefore Cl- may be involved in this effect.

  8. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

    PubMed Central

    Bagot, Rosemary C.; Parise, Eric M.; Peña, Catherine J.; Zhang, Hong-Xing; Maze, Ian; Chaudhury, Dipesh; Persaud, Brianna; Cachope, Roger; Bolaños-Guzmán, Carlos A.; Cheer, Joseph; Deisseroth, Karl; Han, Ming-Hu; Nestler, Eric J.

    2015-01-01

    Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression. PMID:25952660

  9. AAS 228: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note: Lastweek we were at the 228th AAS Meeting in San Diego, CA. Here is a final post aboutselectedevents on the last day of the meeting, written by authors fromastrobites.com, a grad-student collaborative project with which we recently announced a new partnership! Starting in July,keep an eye out for astrobites postsat AAS Nova in between Highlights(i.e., on Tuesdays and Thursdays).Were excited to be working together to bring you more recent astronomy research from AAS journals!Extrasolar Planets: Detection (by Leonardo dos Santos)Thursdays first session on exoplanets was about detecting these distant worlds, and the opening talk was given by Robert Siverd (Las Cumbres Observatory). He describes the NRES, a network of spectrographs that will look for exoplanets using the radial velocity method. One of the coolest aspects of this instrument is that it will feature an on the fly scheduling system that will perform observations as efficiently as possible. The spectrograph is still being tested, but a unit will be deployed at CTIO later this year.@lcogt contracted by @NASA_TESS for follow up of their candidates. #aas228 Jessie Christiansen (@aussiastronomer) June 16, 2016Measuring the depths of transits and eclipses in Spitzer has been problematic in the past, since the Spitzer instrument IRAC (InfraRed Array Camera) has a non-uniform response in its detectors pixels. But, as reported by James Ingalls (Spitzer Science Center, Caltech), observers are circumventing this issue by using what they call the staring mode (avoiding large pointing jumps) and an algorithm to pick sweet spot pixels. Moreover, the results from the IRAC Data Challenge are helping to better understand its behavior. Giuseppe Morello (University College London), on the other hand, explained how his research group gets rid of instrumental effects from IRAC using machine learning. This method removes systematics from exoplanet transit data no matter if the noise source is from an instrument or

  10. Simulation of NO and O2 Transport Facilitated by Polymerized Hemoglobin Solutions in an Arteriole that Takes into Account Wall Shear Stress-induced NO Production

    PubMed Central

    Zhou, Yipin; Cabrales, Pedro; Palmer, Andre F.

    2012-01-01

    A mathematical model was developed to study nitric oxide (NO) and oxygen (O2) transport in an arteriole and surrounding tissues exposed to a mixture of red blood cells (RBCs) and hemoglobin (Hb)-based O2 carriers (HBOCs). A unique feature of this model is the inclusion of blood vessel wall shear stress-induced production of endothelial-derived NO, which is very sensitive to the viscosity of the RBC and HBOC mixture traversing the blood vessel lumen. Therefore in this study, a series of polymerized bovine Hb (PolyHb) solutions with high viscosity, varying O2 affinity, NO dioxygenation rate constants and O2 dissociation rate constants that were previously synthesized and characterized by our group were evaluated via mathematical modeling, in order to investigate the effect of these biophysical properties on the transport of NO and O2 in an arteriole and its surrounding tissues subjected to anemia with the commercial HBOC Oxyglobin® and cell-free bovine Hb (bHb) serving as appropriate controls. The computer simulation results indicated that transfusion of high viscosity PolyHb solutions promoted blood vessel wall shear stress dependent generation of the vasodilator NO, especially in the blood vessel wall and should transport enough NO inside the smooth muscle layer to activate vasodilation compared to the commercial HBOC Oxyglobin® and cell-free bHb. However, NO scavenging in the arteriole lumen was unavoidable due to the intrinsic high NO dioxygenation rate constant of the HBOCs being studied. This study also observed that all PolyHbs could potentially improve tissue oxygenation under hypoxic conditions, while low O2 affinity PolyHbs were more effective in oxygenating tissues under normoxic conditions compared with high O2 affinity PolyHbs. In addition, all ultrahigh molecular weight PolyHbs displayed higher O2 transfer rates than the commercial HBOC Oxyglobin® and cell-free bHb. Therefore, these results suggest that ultrahigh molecular weight PolyHb solutions

  11. Management of afferent loop obstruction from recurrent metastatic pancreatic cancer using a venting gastrojejunostomy

    PubMed Central

    Bakes, Debbie; Cain, Christian; King, Michael; Dong, Xiang Da (Eric)

    2013-01-01

    Pancreatic cancer is an aggressive malignancy potentially curable with surgical intervention. Following pancreaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immediate and delayed problems due to surgical complications and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduodenectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percutaneous biliary decompression. During surgical exploration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical approach for management of this complicated and difficult problem. PMID:24363832

  12. Structure of the Afferent Terminals in Terminal Ganglion of a Cricket and Persistent Homology

    PubMed Central

    Brown, Jacob; Gedeon, Tomáš

    2012-01-01

    We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals) into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets. PMID:22649516

  13. Distribution of primary afferent fibres in the cochlear nuclei. A silver and horseradish peroxidase (HRP) study.

    PubMed Central

    Merchan, M A; Collia, F P; Merchan, J A; Saldana, E

    1985-01-01

    Horseradish peroxidase, when injected intracochlearly, is transported transganglionically to the brain stem cochlear nuclei, thus providing an excellent method for tracing the central projection of the spiral ganglion neurons. Silver impregnation using the Cajal-de Castro method, which stains axons even when inside the bone, was used as a reference technique. The combination of both procedures led to the following conclusions. Primary cochlear afferents are found only in the ventral zone of the dorsal cochlear nucleus. In this area they cover the deep and fusiform cell layers. The molecular layer shows no HRP label. The higher concentration of primary cochlear afferents in the ventral cochlear nucleus appears in its central zone; wide areas in this nucleus are not labelled at all. A thin bundle of primary cochlear afferents runs parallel to, and beneath, the granular region. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:4077711

  14. Management of afferent loop obstruction from recurrent metastatic pancreatic cancer using a venting gastrojejunostomy.

    PubMed

    Bakes, Debbie; Cain, Christian; King, Michael; Dong, Xiang Da Eric

    2013-12-15

    Pancreatic cancer is an aggressive malignancy potentially curable with surgical intervention. Following pancreaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immediate and delayed problems due to surgical complications and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduodenectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percutaneous biliary decompression. During surgical exploration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical approach for management of this complicated and difficult problem.

  15. Central clock excites vasopressin neurons by waking osmosensory afferents during late sleep.

    PubMed

    Trudel, Eric; Bourque, Charles W

    2010-04-01

    Osmoregulated vasopressin release is facilitated during the late sleep period (LSP) to prevent dehydration and enuresis. Previous work has shown that clock neurons in the suprachiasmatic nucleus (SCN) have low firing rates during the LSP, but it is not known how this reduced activity enhances vasopressin release. We found that synaptic excitation of rat supraoptic nucleus neurons by osmosensory afferents is facilitated during the LSP. Stimulation of the SCN at this time inhibited excitatory synaptic currents induced in supraoptic neurons by activation of osmosensory afferents. This effect was associated with an increased rate of synaptic failures and occurred without changes in frequency facilitation, quantal size or in the ratio of postsynaptic responses mediated by AMPA and NMDA receptors. We conclude that clock neurons mediate an activity-dependent presynaptic silencing of osmosensory afferent synapses onto vasopressin neurons and that osmoregulatory gain is enhanced by removal of this effect during late sleep.

  16. Botulinum toxin in migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents.

    PubMed

    Ramachandran, Roshni; Lam, Carmen; Yaksh, Tony L

    2015-07-01

    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi)-SO capsaicin (20 μl of 0.5mM solution) or meningeal capsaicin (4 μl of 0.35 μM). Pre-treatment with ipsi-SO BoNT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; and vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent.

  17. Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1.

    PubMed

    Ditting, Tilmann; Freisinger, Wolfgang; Rodionova, Kristina; Schatz, Johannes; Lale, Nena; Heinlein, Sonja; Linz, Peter; Ott, Christian; Schmieder, Roland E; Scrogin, Karie E; Veelken, Roland

    2016-03-01

    Recently, we showed that renal afferent neurons exhibit a unique firing pattern, i.e., predominantly sustained firing, upon stimulation. Pathological conditions such as renal inflammation likely alter excitability of renal afferent neurons. Here, we tested whether the proinflammatory chemokine CXCL1 alters the firing pattern of renal afferent neurons. Rat dorsal root ganglion neurons (Th11-L2), retrogradely labeled with dicarbocyanine dye, were incubated with CXCL1 (20 h) or vehicle before patch-clamp recording. The firing pattern of neurons was characterized as tonic, i.e., sustained action potential (AP) firing, or phasic, i.e., <5 APs following current injection. Of the labeled renal afferents treated with vehicle, 58.9% exhibited a tonic firing pattern vs. 7.8%, in unlabeled, nonrenal neurons (P < 0.05). However, after exposure to CXCL1, significantly more phasic neurons were found among labeled renal neurons; hence the occurrence of tonic neurons with sustained firing upon electrical stimulation decreased (35.6 vs. 58.9%, P < 0.05). The firing frequency among tonic neurons was not statistically different between control and CXCL1-treated neurons. However, the lower firing frequency of phasic neurons was even further decreased with CXCL1 exposure [control: 1 AP/600 ms (1-2) vs. CXCL1: 1 AP/600 ms (1-1); P < 0.05; median (25th-75th percentile)]. Hence, CXCL1 shifted the firing pattern of renal afferents from a predominantly tonic to a more phasic firing pattern, suggesting that CXCL1 reduced the sensitivity of renal afferent units upon stimulation. Copyright © 2016 the American Physiological Society.

  18. The CYP450 hydroxylase pathway contributes to P2X receptor-mediated afferent arteriolar vasoconstriction.

    PubMed

    Zhao, X; Inscho, E W; Bondlela, M; Falck, J R; Imig, J D

    2001-11-01

    This study was conducted to test the hypothesis that the cytochrome P-450 (CYP450) metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to the afferent arteriolar response to P2 receptor activation. Afferent arteriolar responses to ATP, the P2X agonist, alpha,beta-methylene ATP and the P2Y agonist UTP were determined before and after treatment with the selective CYP450 hydroxylase inhibitor, N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE). Stimulation with 1.0 and 10 microM ATP elicited an initial preglomerular vasoconstriction of 12 +/- 1% and 45 +/- 4% and a sustained vasoconstriction of 11 +/- 1% and 11 +/- 2%, respectively. DDMS or 20-HEDE significantly attenuated the sustained afferent arteriolar constrictor response to ATP. alpha,beta-Methylene ATP (1 microM) induced a rapid initial afferent vasoconstriction of 64 +/- 3%, which partially recovered to a stable diameter 10 +/- 1% smaller than control. Both DDMS and 20-HEDE significantly attenuated the initial vasoconstriction and abolished the sustained vasoconstrictor response to alpha,beta-methylene ATP. UTP decreased afferent diameter by 50 +/- 5% and 20-HEDE did not change this response. In addition, the ATP-induced increase in the intracellular Ca2+ concentration in preglomerular microvascular smooth muscle cells was significantly attenuated by 20-HEDE. Taken together, these results are consistent with the hypothesis that the CYP450 metabolite 20-HETE participates in the afferent arteriolar response to activation of P2X receptors.

  19. Differential action of (-)-baclofen on the primary afferent depolarization produced by segmental and descending inputs.

    PubMed

    Quevedo, J; Eguibar, J R; Jiménez, I; Rudomin, P

    1992-01-01

    The purpose of the present series of experiments was to analyze, in anesthetized and paralyzed cats, the effects of (-)-baclofen and picrotoxin on the primary afferent depolarization (PAD) generated in single Ib afferent fibers by either intraspinal microstimulation or stimulation of the segmental and descending pathways. PAD was estimated by recording dorsal root potentials and by measuring the changes in the intraspinal activation threshold of single Ib muscle afferent fibers. The PAD elicited by stimulation of group I muscle or cutaneous afferents was readily depressed and often abolished 20-40 min after the intravenous injection of 1-2 mg/kg (-)-baclofen. In contrast, the same amounts of (-)-baclofen produced a relatively small depression of the PAD elicited by stimulation of the brainstem reticular formation (RF). The monosynaptic PAD produced in single Ib fibers by intraspinal microstimulation within the intermediate nucleus was depressed and sometimes abolished following the i.v. injections of 1-2 mg/kg (-)-baclofen. Twenty to forty minutes after the i.v. injection of picrotoxin (0.5-1 mg/kg), there was a strong depression of the PAD elicited by stimulation of muscle and cutaneous afferents as well as of the PAD produced by stimulation of the RF and the PAD produced by intraspinal microstimulation. The results obtained suggest that, in addition to its action on primary afferents, (-)-baclofen may depress impulse activity and/or transmitter release in a population of last-order GABAergic interneurons that mediate the PAD of Ib fibers. The existence of GABAb autoreceptors in last-order interneurons mediating the PAD may function as a self-limiting mechanism controlling the synaptic efficacy of these interneurons.

  20. Interactions between cutaneous and muscle afferent projections to cerebral cortex in man.

    PubMed

    Burke, D; Gandevia, S C; McKeon, B; Skuse, N F

    1982-04-01

    In order to demonstrate interactions between cutaneous and muscle afferent volleys in the ascending somatosensory pathways, different nerves of the lower limb were stimulated together in a conditioning-test paradigm, the changes in the earliest component of the cerebral potential evoked by the test stimulus being taken to indicate such an interaction. It was first confirmed that the cerebral potential evoked by stimulation of the posterior tibial nerve at the ankle is derived from muscle afferents in the mixed nerve and has shorter latencies than the cerebral potential evoked by purely cutaneous volleys in the sural nerve (see Burke et al. 1981). Complete suppression of the cerebral potential evoked by stimulation of muscle or cutaneous afferents was produced by conditioning volleys in a different nerve or in a different fascicle of the same nerve. The major factors determining the degree of suppression were found to be the relative sizes of the conditioning and test volleys and their timing, rather than whether the volleys were of cutaneous or muscular origin. It is concluded that the transmission of cutaneous or muscle afferent volleys to cortex can be profoundly altered in normal subjects by conditioning activity. The possibility that normal background afferent activity can similarly modify afferent transmission has implications for diagnostic studies, particularly when they are performed under non-standard conditions, such as in the operating theatre or intensive care unit. It is also concluded that, although a subject may perceive cutaneous paraesthesiae when the posterior tibial nerve is stimulated at the ankle, there may be no cutaneous component to the evoked cerebral potential.

  1. EARLY POSTNATAL OVERNUTRITION: POTENTIAL ROLES OF GASTROINTESTINAL VAGAL AFFERENTS AND BRAIN-DERIVED NEUROTROPHIC FACTOR

    PubMed Central

    Fox, Edward A.; Biddinger, Jessica E.

    2012-01-01

    Abnormal perinatal nutrition (APN) results in a predisposition to develop obesity and the metabolic syndrome and thus may contribute to the prevalence of these disorders. Obesity, including that which develops in organisms exposed to APN, has been associated with increased meal size. Vagal afferents of the gastrointestinal (GI) tract contribute to regulation of meal size by transmitting satiation signals from gut-to-brain. Consequently, APN could increase meal size by altering this signaling, possibly through changes in expression of factors that control vagal afferent development or function. Here two studies that addressed these possibilities are reviewed. First, meal patterns, meal microstructure, and the structure and density of vagal afferents that innervate the intestine were examined in mice that experienced early postnatal overnutrition (EPO). These studies provided little evidence for EPO effects on vagal afferents as it did not alter meal size or vagal afferent density or structure. However, these mice exhibited modest hyperphagia due to a satiety deficit. In parallel, the possibility that brain-derived neurotrophic factor (BDNF) could mediate APN effects on vagal afferent development was investigated. Brain-derived neurotrophic factor was a strong candidate because APN alters BDNF levels in some tissues and BDNF knockout disrupts development of vagal sensory innervation of the GI tract. Surprisingly, smooth muscle-specific BDNF knockout resulted in early-onset obesity and hyperphagia due to increases in meal size and frequency. Microstructure analysis revealed decreased decay of intake rate during a meal in knockouts, suggesting loss of vagal negative feedback contributed to their increase in meal size. However, meal-induced c-Fos activation within the dorsal vagal complex suggested this effect could be due to augmentation of vago-vagal reflexes. A model is proposed to explain how high-fat diet consumption produces increased obesity in organisms exposed

  2. Botulinum toxin in Migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents

    PubMed Central

    Roshni, Ramachandran; Carmen, Lam; Yaksh Tony, L

    2015-01-01

    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi) -SO capsaicin (2.5 μg/30 μl) or meningeal capsaicin (4 μl of 1mg/ml). Pre-treatment with ipsi-SO BONT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent. PMID:25958249

  3. The innate response to peanut extract in ovine afferent lymph and its correlation with allergen sensitisation.

    PubMed

    Van Gramberg, Jenna L; Bischof, Robert J; O'Hehir, Robyn E; de Veer, Michael J; Meeusen, Els N

    2015-07-01

    The innate response generated after initial allergen exposure is crucial for polarising adaptive immunity, but little is known about how it drives an atopic or type-2 immune response. The present study characterises the response of skin-draining afferent lymph in sheep following injection with peanut (PN) extract in the presence or absence of aluminium hydroxide (AlOH) adjuvant. Lymph was collected and innate cell populations characterised over an 84 h time period. The innate response to PN extract in afferent lymph displayed an early increase in neutrophils and monocytes without any changes in the dendritic cell (DC) population. PN antigen was transported by neutrophils and monocytes for the first 36 h, after which time DCs were the major antigen trafficking cells. AlOH adjuvant gradually increased antigen uptake by DCs at the later time points. Following lymphatic characterisation, sheep were sensitised with PN extract by three subcutaneous injections of PN in AlOH, and the level of PN-specific immunoglobulin E (IgE) was determined. Sheep with higher levels of steady-state DCs in afferent lymph showed increased monocytic recruitment in afferent lymph and reduced PN-specific IgE following sensitisation. In addition, DCs from afferent lymph that had ingested PN antigen increased the expression of monocyte chemoattractant mRNA. The results of this study show that the innate response to PN extract involves a dynamic change in cell populations in the afferent lymph over time. In addition, DCs may determine the strength of the initial inflammatory cell response, which in turn may determine the nature of the antigen-specific adaptive response.

  4. Direct and Indirect Regulation of Spinal Cord Ia Afferent Terminal Formation by the γ-Protocadherins.

    PubMed

    Prasad, Tuhina; Weiner, Joshua A

    2011-01-01

    The Pcdh-γ gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons (MNs), do not undergo excessive apoptosis in Pcdh-γ(del/del) null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in Pcdh-γ mutants appear clumped, and fill the space between individual MNs; quantitative analysis shows a ~2.5-fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons (vINs), many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-γ null mice by introduction of a Bax null allele. This indicates that loss of vINs, which act as collateral Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-γ cluster using conditional mutants and multiple Cre transgenic lines (Wnt1-Cre for sensory neurons; Pax2-Cre for vINs; Hb9-Cre for MNs) also revealed a direct requirement for the γ-Pcdhs in Ia neurons and vINs, but not in MNs themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of vINs that act as collateral Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target vINs.

  5. AAS 227: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 4 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Helen B. Warner Prize: Origins of Structure in Planetary Systems (by Erika Nesvold)Another excellent prize lecture started off todays sessions. The Helen B. Warner Prize is awarded for achievement in observational or theoretical astrophysics by a young researcher (no more than eight years after their Ph.D.). This years Warner Prize was presented to Ruth Murray-Clay of UC Santa Barbara. For her award lecture, Murray-Clay told us all about planetary system architecture: the number, masses, and orbits of planets in a given system.Ruth Murray-Clay [photo from http://web.physics.ucsb.edu/ ~murray/biocv.html]The underlying question motivating this type of research is: How rare is the Solar System? In other words, how likely is it that a given planetary system will have rocky planets close to their star, gas giants farther out, and ice giants at the outer reaches of the system? Answering this question will help us solve the physics problem of how and where planets form, and will also help us on our search for other planets like Earth.The data on exoplanet population from transit and radial velocity observations and from direct imaging tell us that our Solar System is not common (many systems we observe have much more eccentric gas giants), but that doesnt

  6. Allodynia mediated by C-tactile afferents in human hairy skin

    PubMed Central

    Nagi, Saad S; Rubin, Troy K; Chelvanayagam, David K; Macefield, Vaughan G; Mahns, David A

    2011-01-01

    Abstract We recently showed a contribution of low-threshold cutaneous mechanoreceptors to vibration-evoked changes in the perception of muscle pain. Neutral-touch stimulation (vibration) of the hairy skin during underlying muscle pain evoked an overall increase in pain intensity, i.e. allodynia. This effect appeared to be dependent upon cutaneous afferents, as allodynia was abolished by intradermal anaesthesia. However, it remains unclear whether allodynia results from activation of a single class of cutaneous afferents or the convergence of inputs from multiple classes. Intriguingly, no existing human study has examined the contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical observations were made in 29 healthy subjects (18 males and 11 females). Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz–200 μm) was applied to the hairy skin overlying TA. Pain ratings were recorded using a visual analogue scale (VAS). In order to evaluate the role of myelinated and unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia, compression block of the sciatic nerve, and low-dose intradermal anaesthesia (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle pain by gentle brushing (1.0 and 3.0 cm s−1) – known to excite CT fibres – was examined. Brushing stimuli were applied to the hairy skin with all fibres intact and following the blockade of myelinated afferents. During tonic muscle pain (VAS 4–6), vibration evoked a significant and reproducible increase in muscle pain (allodynia) that persisted following compression of myelinated afferents. During compression block, the sense of vibration was abolished, but the vibration-evoked allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous afferents abolished the allodynia, whereas the percept of vibration remained unaffected

  7. Central distribution of nociceptive intradental afferent nerve fibers in the rat.

    PubMed

    Bombardi, C; Chiocchetti, R; Brunetti, O; Grandis, A; Lucchi, M L; Bortolami, R

    2006-08-01

    The central distribution of intradental afferent nerve fibers was investigated by combining electron microscopic observations with a selective method for inducing degeneration of the A delta- and C-type afferent fibers. Degenerating terminals were found on the proprioceptive mesencephalic trigeminal neurons and on dendrites in the neuropil of the trigeminal motor nucleus after application of capsaicin to the rat's lower incisor tooth pulp. The results give anatomical evidence of new sites of central projection of intradental A delta- and C-type fibers whereby the nociceptive information from the tooth pulp can affect jaw muscle activity.

  8. A quantitative study of the central projection patterns of unmyelinated ventral root afferents in the cat.

    PubMed Central

    Häbler, H J; Jänig, W; Koltzenburg, M; McMahon, S B

    1990-01-01

    1. The ventral roots of the spinal cord contain a large number of unmyelinated primary afferent neurones. There is some controversy, however, about the function of these fibres and the route of their central projection. Here we have used electrophysiological techniques to quantify the central projection patterns of these neurones in the segment S2 of adult chloralose-anaesthesized cats. 2. A total of 1185 single unmyelinated units were recorded in small filaments isolated from intact and de-efferented ventral roots or intact dorsal roots of the segment S2 in nineteen cats. The projection patterns of these neurones were tested using supramaximal electrical stimulation of the pelvic and pudendal nerve (the main tributaries of the spinal nerve of this segment) and of the segmental companion root (dorsal or ventral as appropriate). 3. The principal finding of this study is that 85% of unmyelinated afferent axons in the ventral root are direct and exclusive projections. They constitute a separate class of afferents which is only capable of transmitting information from the periphery via the ventral roots. However, the proportion of these fibres that enter the central nervous system is unknown and it seems likely that some of them peter out as they approach the spinal cord and end blindly. The functional role of such afferents remains obscure. 4. For the remaining 15% of unmyelinated ventral root afferents, a projection into the segmental dorsal root was found. The majority of those fibres (about two-thirds) are primary afferent neurones innervating the pia mater. Some of these units had a small spot-like receptive field and responded to mechanical stimuli such as pressure and stretch of the root. They did not have axon projections in a peripheral nerve. 5. A few (5%) unmyelinated ventral root fibres are collateral branches of normal primary afferents projecting through the dorsal root. These trifurcating neurones are a small population which make up only some 0.5% of

  9. The organization of primary afferent depolarization in the isolated spinal cord of the frog

    PubMed Central

    Carpenter, D. O.; Rudomin, P.

    1973-01-01

    1. The organization of primary afferent depolarization (PAD) produced by excitation of peripheral sensory and motor nerves was studied in the frog cord isolated with hind limb nerves. 2. Dorsal root potentials from sensory fibres (DR-DRPs) were evoked on stimulation of most sensory nerves, but were largest from cutaneous, joint and flexor muscle afferents. With single shock stimulation the largest cutaneous and joint afferent fibres gave DR-DRPs, but potentials from muscle nerves resulted from activation of sensory fibres with thresholds to electrical stimulation higher than 1·2-1·5 times the threshold of the most excitable fibres in the nerve. This suggests that PAD from muscle afferents is probably due to excitation of extrafusal receptors. 3. Dorsal root potentials produced by antidromic activation of motor fibres (VR-DRPs) were larger from extensor muscles and smaller or absent from flexor muscles. The VR-DRPs were produced by activation of the lowest threshold motor fibres. 4. Three types of interactions were found between test and conditioning DRPs from the same or different nerves. With maximal responses occlusion was usually pronounced. At submaximal levels linear summation occurred. Near threshold the conditioning stimulus frequently resulted in a large facilitation of the test DRP. All three types of interactions were found with two DR-DRPs, two VR-DRPs or one DR-DRP and one VR-DRP. 5. The excitability of sensory nerve terminals from most peripheral nerves was increased during the DR-DRP. The magnitude of the excitability increase varied roughly with the magnitude of the DR-DRP evoked by the conditioning stimulus. 6. There was a marked excitability increase of cutaneous and extensor muscle afferent terminals during the VR-DRP. Flexor muscle afferent terminals often showed no excitability changes to ventral root stimulation. In those experiments where afferent terminals from flexor muscles did show an excitability increase, the effects were smaller than

  10. Spatial orientation of semicircular canals and afferent sensitivity vectors in pigeons

    NASA Technical Reports Server (NTRS)

    Dickman, J. D.

    1996-01-01

    Rotational head motion in vertebrates is detected by the semicircular canal system, whose innervating primary afferent fibers carry information about movement in specific head planes. The semicircular canals have been qualitatively examined over a number of years, and the canal planes have been quantitatively characterized in several animal species. The present study first determined the geometric relationship between individual semicircular canals and between the canals and the stereotactic head planes in pigeons. Stereotactic measurements of multiple points along the circumference of the bony canals were taken, and the measured points fitted with a three-dimensional planar surface. Direction normals to the plane's surface were calculated and used to define angles between semicircular canal pairs. Because of the unusual shape of the anterior semicircular canals in pigeons, two planes, a major and a minor, were fitted to the canal's course. Calculated angle values for all canals indicated that the horizontal and posterior semicircular canals are nearly orthogonal, but the anterior canals have substantial deviations from orthogonality with other canal planes. Next, the responses of the afferent fibers that innervate each of the semicircular canals to 0.5 Hz sinusoidal rotation about an earth-vertical axis were obtained. The head orientation relative to the rotation axis was systematically varied so that directions of maximum sensitivity for each canal afferent could be determined. These sensitivity vectors were then compared with the canal plane direction normals. The afferents that innervated specific semicircular canals formed homogeneous clusters of sensitivity vectors in different head planes. The horizontal and posterior afferents had average sensitivity vectors that were largely co-incident with the innervated canal plane direction normals. Anterior canal afferents, however, appeared to synthesize contributions from the major and minor plane components of the

  11. Afferent lymphatic cannulation as a model system to study innate immune responses to infection and vaccination.

    PubMed

    Neeland, Melanie R; Meeusen, Els N T; de Veer, Michael J

    2014-03-15

    The afferent lymphatics consist of the cells and immunomodulatory signals that are involved in the early response to peripheral stimuli. Examination of this compartment in both homeostatic and stimulatory conditions permits the analysis of the innate biological pathways responsible for the generation of an adaptive immune response in the lymph node. Afferent lymphatic cannulation is therefore an ideal model system to study cellular migration and antigen dispersal kinetics during infection and vaccination. Utilisation of these lymphatic cannulation models has demonstrated the ability to both increase current understanding of infectious diseases, vaccine delivery systems and has the potential to target effector cells and molecules that may be used as novel therapeutic or vaccine targets.

  12. Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction.

    PubMed

    Tang, Yi-Da; Kuzman, James A; Said, Suleman; Anderson, Brent E; Wang, Xuejun; Gerdes, A Martin

    2005-11-15

    Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure. Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV intern