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  1. The atrial natriuretic factor.

    PubMed Central

    Genest, J

    1986-01-01

    In less than three years since the rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats was reported the factor responsible for the diuretic, natriuretic, and vasodilating activity of the atrial homogenates was isolated, its chemical structure elucidated, and its total synthesis achieved. Also the cDNA and the gene encoding for the atrial natriuretic factor in mice, rats, and man have been cloned and the chromosomal site identified. The major effects of this hormone are vasodilatation, prevention and inhibition of the contraction induced by noradrenaline and angiotensin II, diuresis, and natriuresis associated in most instances with a pronounced increase in glomerular filtration rate and filtration fraction, inhibition of aldosterone secretion, and considerable stimulation of particulate guanylate cyclase activity. High density specific binding sites have been demonstrated in the zona glomerulosa of the adrenal cortex, in the renal glomeruli, and in the collecting ducts, and in the brain areas involved in the regulation of blood pressure and of sodium and water (AV3V region, subfornical organ, nucleus tractus solitarius, area postrema). Images Fig 1 Fig 5 PMID:2945572

  2. Involvement of the atrial natriuretic peptide in cardiovascular pathophysiology and its relationship with exercise

    PubMed Central

    2012-01-01

    In this minireview we describe the involvement of the atrial natriuretic peptide (ANP) in cardiovascular pathophysiology and exercise. The ANP has a broad homeostatic role and exerts complex effects on the cardio-circulatory hemodynamics, it is produced by the left atrium and has a key role in regulating sodium and water balance in mammals and humans. The dominant stimulus for its release is atrial wall tension, commonly caused by exercise. The ANP is involved in the process of lipolysis through a cGMP signaling pathway and, as a consequence, reducing blood pressure by decreasing the sensitivity of vascular smooth muscle to the action of vasoconstrictors and regulate fluid balance. The increase of this hormone is associated with better survival in patients with chronic heart failure (CHF). This minireview provides new evidence based on recent studies related to the beneficial effects of exercise in patients with cardiovascular disease, focusing on the ANP. PMID:22313592

  3. The atrial natriuretic peptide: a changing view.

    PubMed

    Rubattu, S; Volpe, M

    2001-11-01

    The atrial natriuretic peptide (ANP), a component of the natriuretic peptide family, was discovered in 1981 when de Bold and his coworkers observed a natriuretic effect induced by infusion of atrial extracts in rats. Subsequently, an impressive amount of research has been carried out in order to identify the structure of the active peptide and its receptors, to characterize the biological functions of ANP and its involvement in the pathophysiology of diseases and, finally, its direct contributory role in the pathogenesis of some cardiovascular disorders. ANP plays a key role in the regulation of salt and water balance, as well as of blood pressure homeostasis. In addition, ANP is involved in the pathophysiology of hypertension and heart failure, and exerts a cellular antiproliferative effect in the cardiovascular system. More recently, a direct contributory role of ANP in the development of hypertension and of cerebrovascular disorders has been suggested by the use of molecular genetic approaches. Therefore, our understanding of the pathophysiologic relevance of ANP has changed over time, finally leading to the identification of ANP as a potential determinant of cardiovascular diseases, rather than as a simple marker of cardiac and vascular dysfunctions. This novel view of ANP may open interesting research pathways.

  4. Insulin blunts the natriuretic action of atrial natriuretic peptide in hypertension.

    PubMed

    Abouchacra, S; Baines, A D; Zinman, B; Skorecki, K L; Logan, A G

    1994-06-01

    Hyperinsulinemia and insulin resistance are implicated in the etiology of hypertension, but the mechanisms involved have not been established. The objectives of this study were to determine whether untreated essential hypertensive patients are more sensitive to the antinatriuretic action of insulin and more resistant to the counteracting natriuretic effect of atrial natriuretic peptide in contrast to age- and sex-matched normotensive control subjects. Urinary sodium excretion was measured at baseline, during hyperinsulinemic euglycemic clamp, and during coadministration of insulin and atrial natriuretic peptide. Baseline urinary sodium excretion was not significantly different in the normotensive subjects (415 +/- 47 mumol/min, n = 12) and hypertensive patients (381 +/- 18 mumol/min, n = 10); with the institution of insulin infusion, there was a similar and significant decline from baseline (P < .001) to 289 +/- 35 mumol/min in normotensive subjects and 235 +/- 17 mumol/min in hypertensive patients. Atrial natriuretic peptide was able to oppose the antinatriuretic action of insulin in normotensive subjects, increasing urinary sodium excretion significantly to a mean level of 352 +/- 31 mumol/min (P < .05), which did not differ significantly from baseline. In the hypertensive group, atrial natriuretic peptide infusion had no effect on urinary sodium excretion (238 +/- 18 mumol/min), and the difference from baseline remained highly significant (P < .001). The hypertensive patients were significantly less insulin sensitive than their normotensive counterparts, as reflected by a lower glucose utilization rate and higher mean baseline plasma insulin level (P < .05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Atrial natriuretic factor and body water distribution.

    PubMed

    Vidal, N A; Arranz, C T; Mones Sias, M C; Herrmann, A P; Martinez Seeber, A

    1987-11-01

    In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.

  6. Possible involvement of atrial natriuretic factor in the antihypertensive action of a high-calcium diet in spontaneously hypertensive and Wistar-Kyoto rats.

    PubMed

    Kohno, M; Murakawa, K; Yasunari, K; Yokokawa, K; Kurihara, N; Takeda, T

    1989-10-01

    The present study was designed to determine the possible involvement of atrial natriuretic factor (ANF) in the hypotensive action of a high-calcium diet. The effects of increased dietary calcium (2.9% calcium, HCa) on blood pressure, urinary sodium excretion, and ANF were examined in 30 spontaneously hypertensive rats (SHR) and 30 Wistar-Kyoto rats (WKY). Control groups of 30 SHR and 30 WKY were fed normal calcium lab chow (0.4% calcium, NCa). The HCa diet reduced blood pressure and serum phosphorus concentration and increased urinary excretion of sodium and calcium in SHR and WKY. The HCa diet also caused a sustained increase in plasma ANF concentration and, finally, a decrease in atrial ANF concentration in both groups. A significant inverse correlation was observed between ANF concentrations in plasma and atria of the four experimental groups. Plasma ANF concentration was positively correlated with daily calcium consumption, and blood pressure was inversely correlated with daily calcium consumption in HCa- and NCa-SHR groups and in HCa- and NCa-WKY groups, respectively. Furthermore, a significant inverse correlation between blood pressure and plasma ANF concentration was observed in SHR groups and in WKY groups, respectively. The observed sustained increment in endogenous plasma ANF concentration, which is probably caused by increased secretion from the atrium, may contribute, in part, to the blood-pressure-lowering effects of the HCa diet.

  7. Receptor imaging with atrial natriuretic peptide. Part 1: High specific activity iodine-123-atrial natriuretic peptide.

    PubMed

    Lambert, R; Willenbrock, R; Tremblay, J; Bavaria, G; Langlois, Y; Hogan, K; Tartaglia, D; Flanagan, R J; Hamet, P

    1994-04-01

    Atrial natriuretic peptide (ANP) was labeled in high specific activity using 123I (p,2n). The biodistribution of 123I-ANP was studied in green vervet monkeys by gamma scintigraphy and in rats by dissection and gamma counting. Iodine-125-ANP was also studied in monkeys by in vitro autoradiography. Iodine-123-ANP showed rapid blood clearance with localization to ANP receptors in the kidneys and lungs, which accounted for 35% of total uptake. In vivo competition imaging studies using cold ANP99-126 and C-ANP102-121 proved that uptake is receptor mediated and allowed imaging of the differential biodistribution of A/B and C-ANP receptor families. Thus, it was possible through the use of selective receptor occupation to prevent uptake in certain organs and to effectively steer the labeled ANP to others. The observed biodistribution patterns were confirmed by an in vitro study using 125I-ANP in the same monkeys, which correlated the scintigraphic images with receptor distribution. An in vivo biodistribution study in rats showed a profound effect of specific activity on biodistribution, with a cutoff for receptor uptake at less than 3000 Ci/mmole. Gamma scintigraphy with 123I-ANP permits the imaging of ANP receptors in vivo. In contrast to receptor imaging with either organic molecules or antibodies, ANP provides rapid first-pass uptake and substantial accumulation (%dose/organ approximately 20% or greater) in receptors. The key to receptor imaging with peptides is high specific activity. Labeled ANP offers potential as a diagnostic tool for diabetic nephropathy, particularly for quantifying the involvement of glomerular disease.

  8. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  9. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  10. Atrial natriuretic factor increases vascular permeability

    SciTech Connect

    Lockette, W.; Brennaman, B. )

    1990-12-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  11. The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

    PubMed

    Mugnier, Sylvie; Kervella, Morgane; Douet, Cécile; Canepa, Sylvie; Pascal, Géraldine; Deleuze, Stefan; Duchamp, Guy; Monget, Philippe; Goudet, Ghylène

    2009-11-19

    Oviduct epithelial cells (OEC) co-culture promotes in vitro fertilization (IVF) in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1) gametes co-incubated with equine vs porcine OEC, 2) intact cumulus-oocyte complexes vs denuded oocytes, 3) OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4) in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A) in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though osteopontin slightly increased the IVF rates. Our study

  12. The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

    PubMed Central

    2009-01-01

    Background Oviduct epithelial cells (OEC) co-culture promotes in vitro fertilization (IVF) in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. Methods & results In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1) gametes co-incubated with equine vs porcine OEC, 2) intact cumulus-oocyte complexes vs denuded oocytes, 3) OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4) in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A) in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though osteopontin slightly

  13. Guanylyl Cyclase/Atrial Natriuretic Peptide Receptor-A: Role in the Pathophysiology of Cardiovascular Regulation

    PubMed Central

    Pandey, Kailash N.

    2012-01-01

    Atrial natriuretic factor (ANF), also known as atrial natriuretic peptide (ANP), is an endogenous and potent hypotensive hormone that elicits natriuretic, diuretic, vasorelaxant, and anti-proliferative effects, which are important in the control of blood pressure and cardiovascular events. One principal locus involved in the regulatory action of ANP and brain natriuretic peptide (BNP) is guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA). Studies on ANP, BNP, and their receptor, GC-A/NPRA, have greatly increased our knowledge of the control of hypertension and cardiovascular disorders. Cellular, biochemical, and molecular studies have helped to delineate the receptor function and signaling mechanisms of NPRA. Gene-targeted and transgenic mouse models have advanced our understanding of the importance of ANP, BNP, and GC-A/NPRA in disease states at the molecular level. Importantly, ANP and BNP are used as critical markers of cardiac events; however, their therapeutic potentials for the diagnosis and treatment of hypertension, heart failure, and stroke have just begun to be realized. We are now just at the initial stage of molecular therapeutics and pharmacogenomic advancement of the natriuretic peptides. More investigations should be undertaken and ongoing ones be extended in this important field. PMID:21815745

  14. Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

    PubMed

    Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-01-01

    Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

  15. Atrial natriuretic factor-like activity in rat posterior pituitary

    SciTech Connect

    Gutkowska, J.; Debinski, W.; Racz, K.; Thibault, G.; Garcia, R.; Kuchel, O.; Genest, J.; Cantin, M.

    1986-03-05

    The presence of a biologically active peptide: Atrial Natriuretic Factor (ANF) has been demonstrated in rat and human circulation and ANF is considered now as a new hormone. ANF may be involved in body fluid regulation. A very sensitive radioimmunoassay for rat ANF allowed the authors to search for immunoreactive ANF (IR-ANF) in rat posterior pituitary. Serial dilutions of homogenates of rat posterior pituitary showed a good parallelism with a reference curve in a radioimmunoassay system. The IR-ANF was extracted from rat posterior pituitary homogenates by activated Vycor glass beads. The lyophilized extract was purified by HPLC on C/sub 18/ ..mu.. Bondapak column. The HPLC yielded two IR-ANF peaks. Both isolated ANF-like material showed biological activity. The IR-ANF eluted with 33% acetonitrile, inhibited ACTH-stimulated aldosterone secretion with a similar potency as synthetic (Arg 101 - Tyr 126) ANF (0.7 x 10/sup -10/M). A much less potent ANF-like material was found in the second peak eluted with 36% acetonitrile. They conclude that ANF-like material is present in rat posterior pituitary and this suggest a possible role in ANF on AVP secretion directly in situ.

  16. Atrial natriuretic polypeptide-like material in rat lung

    SciTech Connect

    Chang, J.K.; Chang, D.; Xie, C.W.; Song, D.L.; Li, X.R.; Zhang, S.X.; Wang, T.L.; Tang, J.

    1986-03-05

    Atrial natriuretic polypeptide-like immunoreactive material (ANP-IR) was found in rat lung by radioimmunoassay, with the concentration ranging from 0.6-1.2 pmol/g of tissue in each lobe. PAP-immunohistochemical study demonstrated that specific staining of granules for ..cap alpha..-human ANP are mainly located in the muscular layer of the pulmonary vein. Fractionation of lung extract by gel filtration and reserve phase HPLC revealed the presence of multiple forms of ANP-IR, which possibly possessed molecular structure partially different from rat ANP, atriopeptin I and III. Intravenous injection of lung extract induced potent diuresis and natriuresis in rats. These responses could be abolished when the lung extract was preincubated with antiserum for ..cap alpha..-human ANP. Specific binding sites for /sup 125/I-labeled rat ANP were also found in lung membrane preparation by radioreceptor assay. Incubation of synthetic atriopeptin III (10/sup -9/ to 10/sup -6/M) with lung tissue induced 1-28 fold increase in lung cGMP content. The results suggest that ANP-IR and its receptors existing in rat lung may be involved in the regulation of pulmonary function and have a synergic effect with ANP of cardiac origin in the control of water-electrolytes balance.

  17. Assessment of atrial natriuretic peptide resistance in cirrhosis with head-out water immersion and atrial natriuretic peptide infusion.

    PubMed

    Legault, L; Warner, L C; Leung, W M; Logan, A G; Blendis, L M; Skorecki, K L

    1993-02-01

    The nature of sodium retention in cirrhosis complicated by ascites has been studied for the last 30 years. Resistance to the natriuretic action of atrial natriuretic peptide (ANP) may play a potential role in this sodium retention. To further evaluate this possibility, we studied 12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive days after a 7-day period off diuretics while receiving a 20 mmol/day sodium restricted diet. Following a crossover design, patients underwent head-out water immersion (HWI) for 3 h and were infused with a alpha-human ANP for 2 h on 2 consecutive days. Blood and urine samples were collected hourly. Five patients displayed a natriuretic response to HWI, sufficient to achieve negative sodium balance, and these patients were termed responders. Each of these five patients also displayed a natriuretic response to ANP infusion. In contrast, the other seven patients (nonresponders) consistently failed to develop a natriuretic response to either maneuver. The two groups had similar elevations in plasma ANP concentrations, but at baseline differed in terms of plasma sodium, plasma renin activity, and serum aldosterone. Despite higher serum aldosterone concentrations, nonresponders excreted less potassium than responders during the peak effect of the interventions, suggesting greater sodium delivery to the aldosterone-sensitive nephron segment in responders. We conclude that the inability to mount an adequate sodium excretory response to HWI in patients with cirrhosis may be conveyed through increased antinatriuretic factors that decrease the sodium delivery to the medullary collecting duct and inhibit the natriuretic effect of ANP at that site.

  18. Endothelial actions of atrial and B-type natriuretic peptides

    PubMed Central

    Kuhn, Michaela

    2012-01-01

    The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

  19. Endothelial actions of atrial and B-type natriuretic peptides.

    PubMed

    Kuhn, Michaela

    2012-05-01

    The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

  20. Regulation of atrial natriuretic peptide receptors in the rat brain

    SciTech Connect

    Saavedra, J.M.

    1987-06-01

    We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. Quantitative autoradiographic techniques and a /sup 125/I-labeled ligand, /sup 125/I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with /sup 125/I-standards. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function.

  1. Regulation of atrial natriuretic peptide (ANP) secretion

    SciTech Connect

    Ruskoaho, H.; Toth, M.; Lang, R.E.; Unger, Th.; Garten, D.

    1986-03-05

    To investigate the role of calcium, protein kinase C and adenylate cyclase in the ANP secretion, the secretory responses from isolated perfused rat hearts to a calcium channel activator, Bay k8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluomethylphenyl)-2-pyridine-5-carboxylate), the calcium ionophore (A23187), the phorbol ester (12-0-tetradecanoylphorbol-13-acetate, TPA), and to forskolin were studied. ANP in perfusate was measured by radioimmunoassay 10 min before and during the infusion (30 min) of various agents at 2 min intervals. A23187 (5.7 x 10/sup -7/) induced a sharp increase, whereas TPA (0.15 - 1.6 x 10/sup -7/) caused a slowly progressive increase in ANP secretion. 4a-phorbol-12,13-didecanoate, a non-active phorbol ester, had no effect on ANP secretion. Bay k8644 (4 x 10/sup -7/) and forskolin (1 x 10/sup -6/) alone caused small but sustained increase in ANP secretion. The combination of TPA with Bay k8644, forskolin or A23187 stimulated ANP secretion higher than the calculated additive value for each agent. Dibuturyl-cAMP (1.6 x 10/sup -4/) pretreatment also enhanced TPA-induced ANP release. 8-Bromo-cGMP (1.3 x 10/sup -4/) and sodium nitroprusside (9 x 10/sup -5/) alone had no effect, but both attenuated the TPA-induced ANP secretion. The results suggest that atrial cardiocytes possess at least two different secretory pathways for ANP secretion, which are probably dependent on protein kinase C and cyclic AMP.

  2. Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

    PubMed Central

    Shenker, Y; Sider, R S; Ostafin, E A; Grekin, R J

    1985-01-01

    Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake. PMID:2932471

  3. Atrial natriuretic peptide blocks renin response to renal hypotension

    SciTech Connect

    Scheuer, D.A.; Thrasher, T.N.; Quillen, E.W. Jr.; Metzler, C.H.; Ramsay, D.J.

    1987-02-01

    The authors have reported that the renin response to systemic hypotension is inhibited in the presence of elevated atrial pressure and that elevations in atrial pressure of similar or larger magnitude cause graded increases in plasma atrial natriuretic peptide (ANP). Therefore they tested the hypothesis that comparable increments in plasma ANP can inhibit renal hypotension-induced increases in plasma renin activity (PRA) in conscious dogs. Renal perfusion pressure was controlled using cuffs implanted around the abdominal aorta just above the renal arteries. Reducing renal perfusion pressure by 10 or 30% of control caused graded increases in PRA. Infusion of 1-28 rat ANP, which increased plasma ANP by 34.8 +/- 7.5 (SE) pg/ml, eliminated increases in PRA in response to a 10% reduction in renal perfusion pressure and markedly inhibited the response to a 30% pressure reduction. ANP and PRA were measured by radioimmunoassay. These results indicate that increments in plasma ANP which reproduce endogenous release inhibit renal hypotension-induced stimulation of PRA. Furthermore, the results provide an explanation for the inhibition of the renin response to renal hypotension during elevate atrial pressure.

  4. Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle cells.

    PubMed

    Baldini, P M; De Vito, P; Fraziano, M; Mattioli, P; Luly, P; Di Nardo, P

    2002-10-01

    Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF shows antimitogenic effects in different cell types acting through R(2) receptor. Excessive proliferation of smooth muscle cells is a common phenomenon in diseases such as atherosclerosis, but the role of growth factors in the mechanism which modulate this process has yet to be clarified. The potential antimitogenic role of ANF on the cell growth induced by growth factors appears very intriguing. Aim of the present study was to investigate the possible involvement of ANF on rat aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the mechanism involved. Our data show that ANF, at physiological concentration range, inhibits RASM cell proliferation induced by known mitogens such as PDGF and insulin, and the effect seems to be elicited through the modulation of phosphatidic acid (PA) production and MAP kinases involvement. Copyright 2002 Wiley-Liss, Inc.

  5. Influence of resting tension on immunoreactive atrial natriuretic peptide secretion by rat atria superfused in vitro

    SciTech Connect

    Schiebinger, R.J.; Linden, J.

    1986-07-01

    Atrial natriuretic peptide is a potent diuretic hormone secreted by the atria in response to volume expansion. We examined the effect of resting tension on atrial natriuretic peptide secretion by rat atria superfused in vitro. Left atria were hooked between an electrode and force transducer and superfused with medium 199. The atria were studied at a pacing frequency of 0 or 3 Hz. Atrial natriuretic peptide content of the superfusate was measured by radioimmunoassay. In nonpaced and paced atria, increasing resting tension three- to five-fold caused immunoreactive atrial natriuretic peptide secretion to increase by 35 +/- 5% (mean +/- SEM, n = 6, p less than 0.01) and 30 +/- 3% (n = 4, p less than 0.01), respectively. Lowering resting tension by 50% in nonpaced and paced atria lowered immunoreactive atrial natriuretic peptide secretion by 30 +/- 3% (n = 7, p less than 0.01) and 24 +/- 3% (n = 6, p less than 0.01), respectively. To exclude the possibility that release of norepinephrine or acetylcholine from endogenous nerve endings was mediating this effect, the atria were superfused with the combination of propranolol 0.1 microM, phentolamine 1.0 microM, and atropine 10 microM. These concentrations of the antagonists were 125-fold or higher than their Kd for binding to their respective receptors. The antagonists did not block the rise in immunoreactive atrial natriuretic peptide secretion; neither did they inhibit an established rise in immunoreactive atrial natriuretic peptide secretion induced by increasing the resting tension.

  6. Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship?

    PubMed Central

    Choi, Marcelo Roberto; Rukavina Mikusic, Natalia Lucía; Kouyoumdzian, Nicolás Martín; Kravetz, María Cecilia; Fernández, Belisario Enrique

    2014-01-01

    Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization) which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways. PMID:25013796

  7. Natriuretic peptides for the detection of paroxysmal atrial fibrillation

    PubMed Central

    Seegers, Joachim; Zabel, Markus; Grüter, Timo; Ammermann, Antje; Weber-Krüger, Mark; Edelmann, Frank; Gelbrich, Götz; Binder, Lutz; Herrmann-Lingen, Christoph; Gröschel, Klaus; Hasenfuß, Gerd; Feltgen, Nicolas; Pieske, Burkert; Wachter, Rolf

    2015-01-01

    Background and purpose Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study. Methods Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF. Results 244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively. Conclusions NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism. PMID:26288739

  8. The actions of atrial natriuretic factor on the vascular wall.

    PubMed

    Vlasuk, G P; Babilon, R W; Nutt, R F; Ciccarone, T M; Winquist, R J

    1987-08-01

    The actions of atrial natriuretic factor (ANF) on the vascular wall are diverse and show a profound regional heterogeneity. ANF is a potent relaxant of aortic smooth muscle, a response which is associated with activation of particulate guanylate cyclase and elevation in tissue levels of cyclic GMP. However, many large and small muscular arteries and most veins are unresponsive to the peptide. The regional vascular heterogeneity may be due to an altered distribution of high affinity receptors and (or) alterations in the coupling of receptor activation to elevations in cyclic 3',5'-guanosine monophosphate (cGMP). Species differences exist in the structural requirements for receptor activation as well as the effects of infused ANF on peripheral resistance. Although the relaxation to ANF in vitro does not require an intact endothelium, endothelial cells contain multiple receptor subtypes for ANF. Differences amongst tissues and (or) species in the receptor profile for ANF may, in part, explain some of heterogeneity in responsiveness to ANF.

  9. Atrial natriuretic factor in neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Carbonell, X; Figueras, J; Salvia, M D; Esque, M T; Delgado, M P; Jimenez, R

    1993-01-01

    The influence of perinatal asphyxia in the secretion of atrial natriuretic factor (ANF) during the first 6 days of life, and its renal consequences are discussed. Comparison between 20 healthy term neonates and 19 with first--or second--degree hypoxic-ischemic encephalopathy (HIE) is made. Daily controls were performed on clinical and neurological examinations and administration of sodium and fluids. On the first and sixth days of life, 24 hours urine collection, natremia, natriuresis, fractionated excretion of sodium and creatinine clearance were determined. The ANF was performed at 1, 2, 3 and 6 days old, by R.I.A. The full term newborns with HIE showed a peak in ANF values on day two, as does the control group, thereafter maintaining higher levels, with a significant difference on day three and six. No correlation could be found between the ANF levels and the renal variables analyzed.

  10. Is clonidine-induced diuresis mediated by atrial natriuretic factor?

    PubMed

    Pan, L; Gutkowska, J

    1988-09-01

    The effect of intracerebroventricular (ICV) administration of clonidine on urine output, urinary sodium excretion, urinary cGMP, and plasma immunoreactive atrial natriuretic factor (IR-ANF) was studied in conscious, normally hydrated rats. Clonidine treatment evoked a significant dose-dependent increase in urine output. A 20-fold elevation was noted after the highest clonidine dose (2 micrograms/rat). The observed diuresis was accompanied by enhanced sodium excretion, which with the highest dose (2 micrograms) of clonidine increased from 1.6 +/- 0.36 to 39.4 +/- 10.5 meq/liter (P less than 0.001). Plasma IR-ANF rose from 30.7 +/- 8.8 to 113.3 +/- 32.3 pg/ml plasma 5 min after the 0.5 micrograms clonidine dose (P less than 0.05), and urinary cGMP excretion was augmented from 8.49 +/- 4.29 to 27.7 +/- 5.0 pmol/min 1 h after 0.5 micrograms clonidine (P less than 0.05). Pretreatment with peripherally administered anti-ANF serum abolished the diuretic effect of intracerebroventricularly administered clonidine; urine output decreased from 1.49 +/- 0.41 to 0.42 +/- 0.21 ml/h. The urinary cGMP level after anti-ANF serum treatment fell from 25.0 +/- 7.56 to 7.1 +/- 3.5 pmol/min (P less than 0.05). Peripheral pretreatment with the alpha 2-antagonist yohimbine or the opioid antagonist naloxone partially abolished clonidine's diuretic impact: urine output dropped from 1.91 +/- 0.55 to 0.42 +/- 0.18 and 0.46 +/- 0.18 ml/h (P less than 0.05), respectively. At the same time, plasma IR-ANF decreased from 113.3 +/- 32.2 to 30.3 +/- 11.4 after yohimbine and to 24.6 +/- 12.1 pg/ml after naloxone treatment (P less than 0.05). These data suggest that ANF may be involved in the mechanism of diuresis of centrally applied clonidine, which appears to enhance ANF release through its central stimulation of opiate and alpha 2-adrenergic receptors.

  11. Amino acid sequence of atrial natriuretic peptides in human coronary sinus plasma.

    PubMed

    Yandle, T; Crozier, I; Nicholls, G; Espiner, E; Carne, A; Brennan, S

    1987-07-31

    Two atrial natriuretic peptides were purified from pooled human coronary sinus plasma by Sep-Pak extraction, immunoaffinity chromatography and reverse phase HPLC. The amino acid sequences of the two peptides were homologous with 99-126 human atrial natriuretic peptide (hANP) and 106-126 hANP, the latter being most probably linked to 99-105 ANP by the disulphide bond. The molar ratio of the peptides in plasma, as assessed by radioimmunoassay was 10:3.

  12. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

  13. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

  14. Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility.

    PubMed

    Bézie, Y; Mesnard, L; Longrois, D; Samson, F; Perret, C; Mercadier, J J; Laurent, S

    1996-09-12

    We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.

  15. [The interaction of atrial natriuretic peptide with other bioregulators of kidney function in chronic glomerulonephritis in children].

    PubMed

    Kucherenko, A G; Markov, Kh M; Zokirov, N Z; Naumova, V I

    1994-01-01

    A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.

  16. Glucocorticoids and atrial natriuretic factor receptors on vascular smooth muscle.

    PubMed

    Yasunari, K; Kohno, M; Murakawa, K; Yokokawa, K; Takeda, T

    1990-11-01

    The effect of glucocorticoids on the atrial natriuretic factor (ANF)-mediated formation of cyclic guanosine monophosphate (cGMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from the renal arteries of 14-week-old Wistar rats by the explant method. Micromolar concentrations of dexamethasone, given as pretreatment for 48 hours, suppressed the ANF-mediated response. The dexamethasone-induced suppression was detectable at 6 hours and reached a maximum 24 hours after administration in a dose-dependent manner. Inhibitors of protein synthesis blocked this effect of the glucocorticoid. The basal activity of guanylate cyclase in the dexamethasone-treated cells was lower than in the control cells. Other steroids having glucocorticoid action mimicked this suppression of the ANF-mediated response. This suppression was blocked by a glucocorticoid receptor antagonist. The results suggest that glucocorticoids suppress ANF-mediated cGMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis. Suppression of the ANF-mediated response may play a role in glucocorticoid-induced hypertension.

  17. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

    PubMed

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-03-31

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

  18. Atrial natriuretic factor binding sites in experimental congestive heart failure

    SciTech Connect

    Bianchi, C.; Thibault, G.; Wrobel-Konrad, E.; De Lean, A.; Genest, J.; Cantin, M. )

    1989-10-01

    A quantitative in vitro autoradiographic study was performed on the aorta, renal glomeruli, and adrenal cortex of cardiomyopathic hamsters in various stages of heart failure and correlated, in some instances, with in vivo autoradiography. The results indicate virtually no correlation between the degree of congestive heart failure and the density of 125I-labeled atrial natriuretic factor ((Ser99, Tyr126)ANF) binding sites (Bmax) in the tissues examined. Whereas the Bmax was increased in the thoracic aorta in moderate and severe heart failure, there were no significant changes in the zona glomerulosa. The renal glomeruli Bmax was lower in mild and moderate heart failure compared with control and severe heart failure. The proportion of ANF B- and C-receptors was also evaluated in sections of the aorta, adrenal, and kidney of control and cardiomyopathic hamsters with severe heart failure. (Arg102, Cys121)ANF (des-(Gln113, Ser114, Gly115, Leu116, Gly117) NH2) (C-ANF) at 10(-6) M displaced approximately 505 of (Ser99, Tyr126)125I-ANF bound in the aorta and renal glomeruli and approximately 20% in the adrenal zona glomerulosa in both series of animals. These results suggest that ANF may exert a buffering effect on the vasoconstriction of heart failure and to a certain extent may inhibit aldosterone secretion. The impairment of renal sodium excretion does not appear to be related to glomerular ANF binding sites at any stage of the disease.

  19. Atrial natriuretic factor in maternal and fetal sheep

    SciTech Connect

    Cheung, C.Y.; Gibbs, D.M.; Brace, R.A.

    1987-02-01

    To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney.

  20. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    PubMed Central

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  1. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  2. A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis

    SciTech Connect

    Colantonio, D.; Casale, R.; Mammarella, M.; Pasqualetti, P. ); Desiati, P.; De Michele, G. )

    1991-01-01

    The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12{plus minus}15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point, and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion.

  3. Extra-atrial expression of the gene for atrial natriuretic factor.

    PubMed Central

    Gardner, D G; Deschepper, C F; Ganong, W F; Hane, S; Fiddes, J; Baxter, J D; Lewicki, J

    1986-01-01

    Atrial natriuretic factor (ANF) is a group of peptides, originally isolated from the cardiac atria, that have a number of important effects on blood pressure, renal function, and salt balance. In the current study, expression of the ANF gene in certain extra-atrial tissues of the rat has been examined by radioimmunoassay of extracted ANF protein and by blot-hybridization, nuclease S1 analysis, and primer-extension analysis of the ANF mRNA. ANF peptides and mRNA were detected in cardiac ventricles, lung, and pituitary gland at levels generally less than or equal to 1% those of cardiac atria. The ANF transcripts in extra-atrial tissue appear to be very similar to those synthesized in the atria. They are polyadenylylated, are equivalent in overall length (950-1050 nucleotides), and have identical 5' termini. A secondary transcription start site mapping approximately 80 base pairs upstream from the primary start site is employed in atria and to a lesser extent in other tissues. The ANF transcript is present throughout the cardiac ventricles from apex to base and in the septum as well as the ventricular free walls. The transcript is more prevalent in the left ventricle and interventricular septum than in the right ventricle. Immunocytochemistry using various anti-rat ANF antibodies localized ANF immunoreactivity to the atrial myocytes; the ventricular myocytes, particularly along the endothelial surface of the ventricular chamber; perialveolar cells in the lung; and the gonadotropin-producing cells of the pituitary. The data indicate that the capacity for ANF gene expression extends beyond atrial tissue, albeit at much reduced levels, and may suggest alternative, perhaps paraendocrine, functions for the peptide in these tissues. Images PMID:2428040

  4. Binding sites of atrial natriuretic peptide in tree shrew adrenal gland

    SciTech Connect

    Fuchs, E.; Shigematsu, K.; Saavedra, J.M.

    1986-09-01

    Adrenal gland binding sites for atrial natriuretic peptide-(99-126) (ANP) were quantitated in tree shrew (Tupaia belangeri) by incubation of adrenal sections with (3-(/sup 125/I)-iodotyrosyl28) atrial natriuretic peptide-(99-126), followed by autoradiography with computerized microdensitometry. In the adrenal glands, there are three types of ANP binding sites. One is located in the zona glomerulosa (BMax 84 +/- 6 fmol/mg protein; Kd 122 +/- 9 pM); the second in the zona fasciculata and reticularis (BMax 29 +/- 2 fmol/mg protein; Kd 153 +/- 6 pM) and the third in the adrenal medulla (BMax 179 +/- 1 fmol/mg protein; Kd 70 +/- 2 pM). Besides the influence of ANP on the regulation of adrenocortical mineralcorticoid and glucocorticoid secretion our findings raise the possibility for a local site of action of atrial natriuretic peptide in the regulation of adrenomedullary catecholamines in the tree shrew, primates and man.

  5. Functional atrial natriuretic peptide receptor in human adrenal tumor

    SciTech Connect

    Shionoiri, H.; Hirawa, N.; Takasaki, I.; Ishikawa, Y.; Oda, H.; Minamisawa, K.; Sugimoto, K.; Matsukawa, T.; Ueda, S.; Miyajima, E.

    1989-01-01

    The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.

  6. Muscarinic effect of atrial natriuretic peptide on rabbit airways.

    PubMed

    Robichaud, A; Saunier, C; Michoud, M C; du Souich, P

    1993-10-01

    1. The aim of the present work was to investigate under which circumstances atrial natriuretic peptide (ANP) modulates airway resistance. 2. Of the six groups of rabbits (n = 5) studied, three received an infusion of ANP (80 ng min-1 kg-1 i.v.) for a period of 100 min, while the other three were infused with the vehicle. Before receiving the infusion of ANP or the vehicle, the animals were pretreated with atropine (0.5 mg kg-1 i.v.), propranolol (2 mg kg-1 i.v.) or not pretreated. After 75 min of infusion of ANP, bronchoconstriction was induced by inhalation of histamine. Respiratory resistance (Rrs) was measured before and 3, 5, 10, 15 and 20 min post-histamine challenge. 3. Following 75 min of ANP infusion, plasma ANP concentration increased from 153 +/- 52 (mean +/- s.e.mean) to 1441 +/- 203 pg ml-1 (P < 0.05) without affecting baseline Rrs. Control Rrs values (12.5-20.4 cmH2O l-1 s) were significantly increased following the inhalation of histamine (P < 0.001). By themselves, atropine, propranolol or ANP did not modify the histamine-induced increase in Rrs. However, when the animals were pretreated with atropine, ANP infusion significantly reduced the increase in Rrs induced by histamine (30 +/- 2 vs 51 +/- 6 cmH2O l-1 s; P < 0.05). 4. These data suggest that ANP has an indirect modulating effect on the airway smooth muscle and will decrease Rrs when muscarinic receptors are blocked.

  7. Impaired atrial natriuretic peptide-mediated lipolysis in obesity.

    PubMed

    Rydén, M; Bäckdahl, J; Petrus, P; Thorell, A; Gao, H; Coue, M; Langin, D; Moro, C; Arner, P

    2016-04-01

    Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered. Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis. In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men. ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.

  8. Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma

    SciTech Connect

    Yandle, T.G.; Espiner, E.A.; Nicholls, M.G.; Duff, H.

    1986-07-01

    A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used (125I)diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP.

  9. Caffeine-induced diuresis and atrial natriuretic peptides.

    PubMed

    Nussberger, J; Mooser, V; Maridor, G; Juillerat, L; Waeber, B; Brunner, H R

    1990-05-01

    After a single-blind, randomized, cross-over protocol using decaffeinated coffee in a control experiment, the effect of an oral 250-mg caffeine dose on plasma immunoreactive atrial natriuretic peptide (ANF) was assessed in eight healthy students who had been on a methylxanthine-free diet for 1 week. One to 2 h after caffeine ingestion, both systolic blood pressure (SBP) and diastolic BP (DBP) increased by 12 mm Hg while heart rate (HR) also tended to increase. An increase in diuresis and in urinary sodium, potassium, and osmol excretion was observed within 1 h. Decaffeinated coffee induced no change in any of these parameters. Plasma epinephrine (EPI) increased gradually from 16.6 +/- 3.2 pg/ml (mean +/- SEM) to 45.1 +/- 7.9 pg/ml within 2 h after caffeine ingestion, but did not change after decaffeinated coffee (p less than 0.001). Plasma norepinephrine (NE), renin activity (PRA), aldosterone, and vasopressin remained unchanged. Plasma ANF was measured by radioimmunoassay (RIA) using an extremely sensitive antiserum (Kd = 10(-12) M) after rapid and virtually complete (90-103%) extraction from plasma. In 0.2 ml plasma, the theoretical detection limit is 1.1 fmol/ml. Normal plasma ANF concentrations in supine subjects were 17.9 +/- 8.1 fmol/ml (mean +/- SD) and 11.0 +/- 3.3 fmol/ml in subjects in the upright position. Plasma ANF levels were not affected by coffee drinking. In conclusion, by using a new and sensitive assay for plasma ANF, we did not find that caffeine-induced diuresis is mediated by ANF.

  10. Responses of Plasma Atrial Natriuretic Peptide to High Intensity Submaximal Exercise in the Heat,

    DTIC Science & Technology

    1987-06-01

    Natriuretic Peptide to LnHigh Intensity Submaximal Exercise in the Heat 0 " William J. Kraemer. Lawrence E. Armstrong, Roger W. Hubbard. :I[_] Louis J...atriopeptins in rat adrenal cells. Cir Res 57: 113-118. f V-0C -- V- - IF -I 7 - % 7 -. 17 Chartier L. Schiffrin EL. Thibault G (1984). Effects of atrial

  11. Expression of natriuretic peptide receptor mRNA and functional response to atrial natriuretic peptide and C-type natriuretic peptide in rainbow trout (Oncorhynchus mykiss) head kidney leucocytes.

    PubMed

    Powell, M D; McWilliam, H; McLeod, J; Nankervis, S; Butler, R; Toop, T

    2008-04-01

    The stimulatory effect of vasomodulatory natriuretic peptide hormones on macrophages and peripheral blood leucocytes in mammals is well-established. However, the relationship in lower vertebrates has not been characterised. Expression of atrial natriuretic peptide, ventricular natriuretic peptide and C-type natriuretic peptide-1, and the guanylyl cyclase-linked (GC) natriuretic peptide receptor-A and -B-type receptors (NPR-A and NPR-B, respectively) was determined by PCR from the mRNA of rainbow trout head kidney leucocytes yielding gene fragments with 100% homology to the same respective natriuretic peptide and NPR-A and -B sequences obtained from other rainbow trout tissues. A mixed population of isolated rainbow trout head kidney leucocytes was stimulated in vitro with trout atrial natriuretic peptide (specific NPR-A agonist) and trout C-type natriuretic peptide (NPR-A and -B agonist) as well as the cGMP agonist 8-bromo-cGMP or the GC inhibitor 8-bromo-phenyl-eutheno-cGMP. Respiratory burst was stimulated by trout atrial natriuretic peptide, trout C-type natriuretic peptide-1 and 8-bromo-cGMP in a dose dependant manner with the highest activity as a result of stimulation with trout C-type natriuretic peptide-1 in excess of that achieved by phorbol myristate acetate (PMA). Equimolar concentrations of the inhibitor, inhibited the respiratory burst caused by the natriuretic peptides and 8-bromo-cGMP. The natriuretic peptide receptors on rainbow trout head kidney leucocytes appear to have a stimulatory function with regard to respiratory burst that is activated through a cGMP second messenger pathway and the natriuretic peptides expressed in the head kidney leucocytes may well act in a paracrine/autocrine manner.

  12. Atrial natriuretic peptide and vasopressin-presence in the ciliary body of eye in the pig (sus domesticus).

    PubMed

    Valentino, B; Valentino, A; Lipari, L; Lipari, A; Farina, E

    2014-01-01

    The aqueous humor is produced in the ciliary body, therefore in this study we investigated the Atrial natriuretic peptide (ANP) and vasopressin (VP)-presence in the ciliary body of the pig eye since these peptide are involved in the homeostasis of body fluids. The results show ANP-presence in the epithelial cells and in the endothelial cells of the blood vessels and VP-presence in the epithelial cells, in the endothelium of canal of Schelmm and in the muscle cells of the blood vessels. These peptides might regulate the synthesis and the composition of the aqueous humor and regulate the hydrodynamic flow and haemodynamic flow of the blood.

  13. Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

    PubMed Central

    Seidah, N G; Lazure, C; Chrétien, M; Thibault, G; Garcia, R; Cantin, M; Genest, J; Nutt, R F; Brady, S F; Lyle, T A

    1984-01-01

    A substance called atrial natriuretic factor (ANF), localized in secretory granules of atrial cardiocytes, was isolated as four homologous natriuretic peptides from homogenates of rat atria. The complete sequence of the longest form showed that it is composed of 33 amino acids. The three other shorter forms (2-33, 3-33, and 8-33) represent amino-terminally truncated versions of the 33 amino acid parent molecule as shown by analysis of sequence, amino acid composition, or both. The proposed primary structure agrees entirely with the amino acid composition and reveals no significant sequence homology with any known protein or segment of protein. The short form ANF-(8-33) was synthesized by a multi-fragment condensation approach and the synthetic product was shown to exhibit specific activity comparable to that of the natural ANF-(3-33). PMID:6232612

  14. Preeclampsia and maladaptation to pregnancy: a role for atrial natriuretic peptide?

    PubMed

    Spaanderman, M; Ekhart, T; van Eyck, J; de Leeuw, P; Peeters, L

    2001-10-01

    The majority of women with a history of preeclampsia have either an underlying thrombophilic disorder or a vascular disorder. In this study, we tested the hypothesis that only the latter condition predisposes for abnormal hemodynamic adaptation to pregnancy. Thirty-seven formerly preeclamptic subjects were subdivided into a hypertensive (HYPERT, N = 10), a normotensive thrombophilic (THROMB, N = 13) and a normotensive nonthrombophilic subgroup (NONTHROMB, N = 14). In these women and in 10 normal parous controls, the following variables were measured at least five-months postpartum at day 5 (+/-2) of the menstrual cycle and again at five- and seven-weeks amenorrhea in the next pregnancy: mean arterial pressure, heart rate, cardiac output, central cardiovascular dimensions, plasma volume, glomerular filtration rate, effective renal plasma flow, 17-beta estradiol, progesterone, the hormones of the renin-angiotensin-aldosterone (RAAS) axis, catecholamines and alpha-atrial natriuretic peptide. The early pregnancy rise in cardiac output, renal variables, RAAS activity, and plasma volume was comparable in all groups. However, the HYPERT and NONTHROMB subgroups differed from controls by a lower plasma volume in the prepregnant state. In addition, only the women in these two subgroups responded to pregnancy by a rise in circulating alpha-atrial natriuretic peptide. In addition, at seven weeks, in the subjects belonging to the HYPERT and NONTHROMB subgroups, plasma volume was the lowest and correlated inversely with the concomitant circulating level of alpha-atrial natriuretic peptide. The hemodynamic adaptation to pregnancy in the HYPERT and NONTHROMB subgroups differs from that in THROMB and controls by an early pregnancy rise in alpha-atrial natriuretic peptide. As a consequence, the early pregnancy plasma volume expansion in the NONTHROMB and HYPERT subgroups is less than in normal parous controls.

  15. Specific receptor binding of atrial natriuretic peptide to rat renal cortex

    SciTech Connect

    Ogura, T.; Mitsui, T.; Ogawa, N.; Ota, Z.

    1985-09-01

    Radiolabeled receptor assay (RRA) of atrial natriuretic peptide (ANP) was studied in rat kidney membranes. Binding of ( SVI)-ANP to membrane preparations of rat whole kidney was saturated and show a high affinity. Furthermore, renal cortex membrane had a higher affinity for ANP binding site than renal medulla membrane. This high affinity ANP receptor site in renal cortex membrane indicated that ANP controlled the balance of water and sodium excretion due to this receptor site in the kidney.

  16. The expression of atrial natriuretic peptide in the oviduct and its functions in pig spermatozoa.

    PubMed

    Zhang, Meijia; Hong, Haiyan; Zhou, Bo; Jin, Shiying; Wang, Chao; Fu, Maoyong; Wang, Songbo; Xia, Guoliang

    2006-06-01

    Locally synthesized atrial natriuretic peptide (ANP) and its receptors have been found in reproductive tissues of various mammals, and play an important role in the acrosome reaction of human sperm. The objective of the present study was to examine the expression of ANP and its receptors in pig spermatozoa and oviduct, and the effect of ANP on pig spermatozoa function. The expression of ANP and its receptors was analyzed by RT-PCR. Only natriuretic peptide receptors-A (NPRA) mRNA was detected in fresh sperm. While the levels of natriuretic peptide receptors-C (NPRC) mRNA were low with no obvious change among different oviductal phases, the levels of ANP mRNA were high in oviduct(OT)1 , OT3 and OT5, but were very low in OT2. On the other hand, the levels of NPRA mRNA were low in OT1 and OT2, increased in OT3 and reached a maximum in OT4 and OT5. Western blot analysis revealed that the level of ANP was high in OT1, decreased in OT2 and OT3, and arrived at the nadir in OT4 and OT5. The effect of ANP on spermatozoa function was studied by the acrosome reaction and IVF. Incubation with ANP for 1 h significantly induced acrosome reaction of preincubated spermatozoa, and maximal response of acrosome reaction (34.1 +/- 2.3%) was achieved at 1 nM ANP treatment. Both C-ANP-(4-23), a selective ligand of NPRC, and caffeine had no effect on the acrosome reaction. The stimulatory effect of ANP on acrosome reaction could be mimicked by the permeable cGMP analog, 8-Br-cGMP. ANP and caffeine had a similar effect on improving the oocytes penetration rate, polyspermy rate and the average number of sperm per penetrated oocyte. Also, ANP treatment had a similar effect on cleavage rate, blastocyst formation rate and the number of cells per blastocyst as that of caffeine treatment. The effects of ANP on the acrosome reaction and the parameters of oocyte penetration could be blocked by cGMP-dependent protein kinase (PKG) inhibitors KT5823 and/or Rp-8-pCPT-cGMPS. These results suggest that

  17. Expression of the atrial natriuretic peptide gene in the cardiac muscle of rat extrapulmonary and intrapulmonary veins.

    PubMed Central

    Springall, D R; Bhatnagar, M; Wharton, J; Hamid, Q; Gulbenkian, S; Hedges, M; Meleagros, L; Bloom, S R; Polak, J M

    1988-01-01

    Atrial natriuretic peptide is a peptide regulating salt and water balance, originally isolated from the cardiac atrium, where it is synthesised as part of a precursor molecule in specialised myocardial cells. The myocardium extends into the extrapulmonary part of the pulmonary veins in many species, including man. In some small mammals, however, such as the rat, mouse, and bat, it extends further to veins in the peripheral parts of the lung. Since this myocardial layer is continuous with that in the atrium, we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats. Strong immunoreactivity was seen for both the peptide and the N terminal sequence (cardiodilatin) of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point, where it was localised in the dense cored granules by electron microscopy; in situ hybridisation showed atrial natriuretic peptide messenger RNA at identical sites. Chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved (precursor molecule) form. Thus the peptide is synthesised in veins both outside and inside the lung, and these extra-atrial sites may be an important additional source of circulating atrial natriuretic peptide. Images PMID:2965426

  18. Increase in plasma concentrations of cardiodilatin (amino terminal pro-atrial natriuretic peptide) in cardiac failure and during recumbency.

    PubMed Central

    Meleagros, L; Gibbs, J S; Ghatei, M A; Bloom, S R

    1988-01-01

    Plasma concentrations of cardiodilatin, the peptide sequence at the amino terminal of the pro-atrial natriuretic peptide, in 17 normal subjects ranged from 59 to 202 (mean 118 (SEM) (9] pmol/l. Recumbency increased the mean (SEM) concentration to 160 (13) pmol/l. The plasma concentration of cardiodilatin in 24 patients with congestive cardiac failure was much higher (964 (175) pmol/l) than in the normal subjects. It was highest in those with heart failure in New York Heart Association functional classes III and IV and the concentration correlated both with atrial natriuretic peptide concentrations and left ventricular ejection fraction. Concentrations rose during induced tachycardia in three patients tested. Chromatography showed a single clean peak of plasma cardiodilatin immunoreactivity. It seems that cardiodilatin is a second circulating cardiac peptide that is jointly released with atrial natriuretic peptide by common stimuli. Other workers have reported that, like atrial natriuretic peptide, three partial cardiodilatin sequences can stimulate renal particulate guanylate cyclase and increase cyclic guanosine monophosphate. The simultaneous release of cardiodilatin in higher circulating concentrations than atrial natriuretic peptide may be relevant to the finding that appropriate concentrations of exogenous atrial natiuretic peptide alone do not produce the full renal effects associated with endogenous peptide release. PMID:2970269

  19. The impact of atrial natriuretic peptide on anxiety, stress and craving in patients with alcohol dependence.

    PubMed

    Koopmann, Anne; Leménager, Tagrid; Wolf, Nadine Donata; Reinhard, Iris; Hermann, Derik; Koch, Jan; Wiedemann, Klaus; Kiefer, Falk

    2014-01-01

    Atrial natriuretic peptide (ANP) is well known to modulate fluid and electrolyte homeostasis but also to counter-regulate hypothalamic-pituitary-adrenal (HPA) axis activity. Correspondingly, recent studies suggest an important role of ANP in the neurobiology of anxiety. Preclinical and clinical data now provide evidence for an involvement of ANP in the pathophysiology of addictive behavior. The present study aims to elucidate the effects of ANP on alcohol-dependent patients' anxiety, perceived stress and craving during alcohol withdrawal. A sample of 59 alcohol-dependent inpatients was included in the analysis. A blood sample was taken at day 14 of detoxification in order to assess the concentrations of ANP and cortisol in plasma. In parallel, we assessed patients' alcohol craving, using the Obsessive Compulsive Drinking Scale, as well as anxiety (State-Trait Anxiety Inventory). Patients' stress levels were assessed using the Perceived Stress Scale. We found a significant negative association between patients' ANP plasma concentrations and anxiety, craving for alcohol and perceived stress. Regression analyses suggest that ANP is a significant predictor both for patients' perceived stress and for the severity of anxiety during early abstinence. The association of patients' ANP plasma levels and craving is suggested to be mediated by perceived stress. Our results suggest that the association of patients' ANP plasma levels and craving is mediated by their perceived stress. For this reason, intranasal application of ANP may prove to be a new avenue for the treatment of alcohol dependence in patients exhibiting high levels of perceived stress.

  20. Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

    SciTech Connect

    Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.; Mantyh, P.W. )

    1988-09-01

    To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific binding of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

  1. Pro-atrial natriuretic peptide and prediction of atrial fibrillation and stroke: The Malmö Preventive Project.

    PubMed

    Berntsson, John; Smith, J Gustav; Nilsson, Peter M; Hedblad, Bo; Melander, Olle; Engström, Gunnar

    2017-01-01

    Background The increasing prevalence of atrial fibrillation and novel therapeutic tools to prevent cardioembolic stroke has increased the need for risk markers. Objectives This study explored the relationship between the midregional sequence of pro-atrial natriuretic peptide (MR-proANP) levels with the risk of atrial fibrillation and stroke, and whether measurement of MR-proANP improves the prediction of these outcomes. Methods MR-proANP was measured in fasting blood samples of 5130 subjects (69% men, mean age 69.2 ± 6.2 years) without a history of atrial fibrillation or stroke from the general population. The incidence of atrial fibrillation and stroke was monitored over a median follow-up of 5.6 years. C-statistics and net reclassification improvement was used to assess the predictive ability of MR-proANP in addition to conventional risk factors. Results Log-normalized MR-proANP was significantly associated with the incidence of atrial fibrillation ( n = 362; hazard ratio (HR); 95% confidence interval (CI) per 1 standard deviation (SD) 2.05, 1.86-2.27) and stroke from all causes ( n = 195; HR 1.30; 95% CI 1.12-1.50). The HR for stroke events related to atrial fibrillation was 1.79 (95% CI 1.25-2.58) per 1 SD. MR-proANP significantly improved the prediction of atrial fibrillation when added to a risk score of conventional risk factors (C statistic 0.69 vs. 0.75), mainly by down-classifying subjects who did not develop atrial fibrillation. A smaller improvement in predictive ability was observed for stroke (C statistic 0.66 vs. 0.68). Conclusion High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population. MR-proANP may be useful to identify individuals with an increased risk of atrial fibrillation.

  2. Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human atrial appendage

    SciTech Connect

    Hamid, Q.; Wharton, J.; Terenghi, G.; Hassall, C.J.S.; Aimi, J.; Taylor, K.M.; Nakazato, H.; Dixon, J.E.; Burnstock, G.; Polak, J.M.

    1987-10-01

    The localization of mRNA encoding preproatrial natriuretic peptide was investigated in tissue sections and cultures of rat heart and in sections of human right atrial appendage using the technique of in situ hybridization with /sup 32/P- and /sup 35/S-labeled RNA probes. Rat atrial natriuretic peptide (ANP) transcripts were demonstrated in numerous atrial myocytes and, to a lesser extent, in ventricular myocytes in both tissue sections and newborn rat heart cultures. These findings are consistent with those obtained by RNA blot analysis of rat heart total RNA, indicating that a single prepro-ANP transcript of approx. 900 nucleotides was present in the ventricles as well as the atria. Using a /sup 35/S-labeled RNA probe for human ANP mRNA, ANP transcripts were also localized to the majority of myocytes in the human right atrial appendage. Only background levels of autoradiographic labeling were obtained when RNA probes identical to the coding sequence of rat or human ANP mRNA were used. A close correlation was found between the distribution of ANP immunoreactivity and prepro-ANP mRNA in these preparations. These results provide unequivocal evidence for the expression of the ANP gene in the rat ventricles, as well as the atria, because myocytes in these tissues have been established as the sites of both ANP localization and precursor biosynthesis. The combined use of cardiac cultures and in situ hybridization may be of value in future studies investigating the regulation of ANP synthesis in cardiac myocytes.

  3. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

  4. Atrial natriuretic factor mRNA and binding sites in the adrenal gland.

    PubMed Central

    Nunez, D J; Davenport, A P; Brown, M J

    1990-01-01

    The factor inhibiting aldosterone secretion produced by the adrenal medulla may be atrial natriuretic factor (ANF), since the latter abolishes aldosterone release in response to a number of secretagogues, including angiotensin II and K+. In this study we have shown that cells in the adrenal medulla contain ANF mRNA and therefore have the potential to synthesize this peptide. The presence of binding sites for ANF predominantly in the adrenal zona glomerulosa suggests that, if ANF is synthesized in the medulla and transferred to the cortex, it may affect mineralocorticoid status. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2146954

  5. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Huls, M. H.; Sams, Clarence F.

    1989-01-01

    In view of the suggestions by Chabrier et al. (1987) and Steardo and Nathanson (1987) that atrial natriuretic peptide (ANP) may play a role in the fluid homeostasis of the brain, the ANP receptors in primary cultures of bovine brain microvessel endothelian cells were quantitated and characterized. Results of partition binding studies and the effect of cGMP additions indicated the presence of at least two types of ANP receptors, with the majority of the receptors being the nonguanylate cyclase coupled receptors. The presence of at least two ANP receptor types suggests an active role for ANP in regulating brain endothelial cell function.

  6. Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension

    NASA Astrophysics Data System (ADS)

    John, Simon W. M.; Krege, John H.; Oliver, Paula M.; Hagaman, John R.; Hodgin, Jeffrey B.; Pang, Stephen C.; Flynn, T. Geoffrey; Smithies, Oliver

    1995-02-01

    To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.

  7. Persistent sexual arousal in a woman with associated cardiac defects and raised atrial natriuretic peptide.

    PubMed

    Bell, C; Richardson, D; Goldmeier, D; Crowley, T; Kocsis, A; Hill, S

    2007-02-01

    The persistent sexual arousal syndrome (PSAS) is a newly described entity where the woman becomes involuntarily genitally aroused for extended periods of time in the absence of sexual desire and is distressed by this situation. The cause of this sexual problem is not well understood. We describe such a case where the subjective feelings were confirmed by observing genital engorgement. In her case, PSAS came on after initiation of fludrocortisone given for hypotension and bradycardia that was associated with an atrial septal defect (ASD). We argue that the combined effect of the ASD and fludrocortisone may be associated with an increase in her levels of atrial natriuretic peptide (ANP). ANP causes profound vasodilation and vascular leakage. We postulate that the high serum levels of ANP in her case may be contributory to her PSAS.

  8. Renal alterations of atrial natriuretic peptide receptors by chronic moderate ethanol treatment.

    PubMed

    Guillaume, P; Than, V D; Gianoulakis, C; Gutkowska, J

    1997-01-01

    Previous studies have shown that chronic moderate ethanol (EtOH) consumption prevents the age-dependent increase in blood pressure. However, the physiological systems mediating the antihypertensive effects of EtOH are not known. The objective of the present studies was to investigate the effects of chronic (8 mo) moderate EtOH consumption on renal natriuretic receptors of spontaneously hypertensive (SHR) and normotensive (WKY) rats, using competitive binding assay and autoradiographic techniques. In the renal glomeruli, the maximal binding capacity (Bmax) of the heterogeneous atrial natriuretic peptide (ANP) receptor population (NPR-A and NPR-C) was significantly lower in EtOH-treated SHR and WKY rats compared with water-treated controls. Quantification of receptor subtypes showed that this decrease was primarily the result of NPR-C down-regulation. The apparent dissociation constant (Kd) was also decreased by the EtOH treatment. In the renal papilla, the Bmax of the homogeneous receptor population (NPR-A) was significantly elevated by long-term EtOH consumption in both strains compared with water-treated controls. However, the Kd was unaltered by the EtOH administration. Thus EtOH treatment induced specific alterations in renal natriuretic receptors that may play a role in the "protective" effect of moderate EtOH consumption on the age-dependent increase in blood pressure.

  9. Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.

    PubMed

    Gelfand, R A; Frank, H J; Levin, E; Pedram, A

    1991-08-01

    The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.

  10. Regulation of expression of atrial and brain natriuretic peptide, biomarkers for heart development and disease.

    PubMed

    Sergeeva, Irina A; Christoffels, Vincent M

    2013-12-01

    The mammalian heart expresses two closely related natriuretic peptide (NP) hormones, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The excretion of the NPs and the expression of their genes strongly respond to a variety of cardiovascular disorders. NPs act to increase natriuresis and decrease vascular resistance, thereby decreasing blood volume, systemic blood pressure and afterload. Plasma levels of BNP are used as diagnostic and prognostic markers for hypertrophy and heart failure (HF), and both ANF and BNP are widely used in biomedical research to assess the hypertrophic response in cell culture or the development of HF related diseases in animal models. Moreover, ANF and BNP are used as specific markers for the differentiating working myocardium in the developing heart, and the ANF promoter serves as platform to investigate gene regulatory networks during heart development and disease. However, despite decades of research, the mechanisms regulating the NP genes during development and disease are not well understood. Here we review current knowledge on the regulation of expression of the genes for ANF and BNP and their role as biomarkers, and give future directions to identify the in vivo regulatory mechanisms. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.

  11. Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males.

    PubMed

    Skov, Jeppe; Holst, Jens Juul; Gøtze, Jens Peter; Frøkiær, Jørgen; Christiansen, Jens Sandahl

    2014-01-01

    The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1-ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP.

  12. Ratio of preoperative atrial natriuretic peptide to brain natriuretic peptide predicts the outcome of the maze procedure in mitral valve disease.

    PubMed

    Sato, Masafumi; Mikamo, Akihito; Kurazumi, Hiroshi; Suzuki, Ryo; Murakami, Masanori; Kobayashi, Toshiro; Yoshimura, Koich; Hamano, Kimikazu

    2013-02-28

    Although the maze procedure is an established surgical treatment for eliminating atrial fibrillation (AF), its efficacy in patients with mitral valve disease has remained unsatisfactory. A useful predictive marker for the outcome of the maze procedure is needed. The aim of this study was to investigate whether the preoperative ratio of atrial natriuretic peptide (ANP) to brain natriuretic peptide (BNP) reflects atrial fibrosis and can be used to predict the maze procedure outcome in patients with mitral valve disease. A total of 23 consecutive patients who underwent the radial approach to the maze procedure combined with mitral valve surgery were included in this study and were divided into a sinus rhythm (SR) group (n=16) and an AF group (n=7) based on postoperative cardiac rhythm. Plasma samples were obtained at rest before the operation and were analysed for ANP and BNP levels. Atrial tissue samples taken during surgery were used to quantify interstitial fibrosis. The preoperative ANP-to-BNP ratio in the SR group was significantly higher than that in the AF group (0.74 +/- 0.29 vs. 0.42 +/- 0.28, respectively; p=0.025). Receiver operating characteristic (ROC) curve analysis was used to identify factors that predict outcomes after the maze procedure. The area under the ROC curve for the ANP-to-BNP ratio (0.81) was greater than for any other preoperative factors. Moreover, the preoperative ANP-to-BNP ratio demonstrated a negative correlation with left atrial fibrosis (r=-0.69; p=0.003). The preoperative ANP-to-BNP ratio can predict maze procedure outcome in patients with mitral valve disease, and it represents a potential biomarker for left atrial fibrosis.

  13. Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart

    PubMed Central

    Azer, John; Hua, Rui; Krishnaswamy, Pooja S; Rose, Robert A

    2014-01-01

    Natriuretic peptides, including B-type and C-type natriuretic peptide (BNP and CNP), are powerful regulators of the cardiovascular system; however, their electrophysiological effects in the heart, particularly in the sinoatrial node (SAN), are incompletely understood. We have used high-resolution optical mapping to measure the effects of BNP and CNP, and the roles of natriuretic peptide receptors (NPR-A, NPR-B and NPR-C), on electrical conduction within the SAN and atrial myocardium. In basal conditions BNP and CNP (50–500 nm) increased conduction velocity (CV) within the SAN by ∼30% at the high dose and shifted the initial exit site superiorly. These effects sped conduction from the SAN to the surrounding atrial myocardium and were mediated by the NPR-A and NPR-B receptors. In the presence of isoproterenol (1 μm) the NPR-C receptor made a major contribution to the effects of BNP and CNP in the heart. In these conditions BNP, CNP and the NPR-C agonist cANF each decreased SAN CV and shifted the initial exit site inferiorly. The effects of cANF (30% reduction) were larger than BNP or CNP (∼15% reduction), indicating that BNP and CNP activate multiple natriuretic peptide receptors. In support of this, the inhibitory effects of BNP were absent in NPR-C knockout mice, where BNP instead elicited a further increase (∼25%) in CV. Measurements in externally paced atrial preparations demonstrate that the effects of natriuretic peptides on CV are partially independent of changes in cycle length. These data provide detailed novel insight into the complex effects of natriuretic peptides and their receptors on electrical conduction in the heart. PMID:24344164

  14. Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart.

    PubMed

    Azer, John; Hua, Rui; Krishnaswamy, Pooja S; Rose, Robert A

    2014-03-01

    Natriuretic peptides, including B-type and C-type natriuretic peptide (BNP and CNP), are powerful regulators of the cardiovascular system; however, their electrophysiological effects in the heart, particularly in the sinoatrial node (SAN), are incompletely understood. We have used high-resolution optical mapping to measure the effects of BNP and CNP, and the roles of natriuretic peptide receptors (NPR-A, NPR-B and NPR-C), on electrical conduction within the SAN and atrial myocardium. In basal conditions BNP and CNP (50-500 nm) increased conduction velocity (CV) within the SAN by ∼30% at the high dose and shifted the initial exit site superiorly. These effects sped conduction from the SAN to the surrounding atrial myocardium and were mediated by the NPR-A and NPR-B receptors. In the presence of isoproterenol (1 μm) the NPR-C receptor made a major contribution to the effects of BNP and CNP in the heart. In these conditions BNP, CNP and the NPR-C agonist cANF each decreased SAN CV and shifted the initial exit site inferiorly. The effects of cANF (30% reduction) were larger than BNP or CNP (∼15% reduction), indicating that BNP and CNP activate multiple natriuretic peptide receptors. In support of this, the inhibitory effects of BNP were absent in NPR-C knockout mice, where BNP instead elicited a further increase (∼25%) in CV. Measurements in externally paced atrial preparations demonstrate that the effects of natriuretic peptides on CV are partially independent of changes in cycle length. These data provide detailed novel insight into the complex effects of natriuretic peptides and their receptors on electrical conduction in the heart.

  15. Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia

    SciTech Connect

    Lubbesmeyer, H.J.; Woodson, L.; Traber, L.D.; Flynn, J.T.; Herndon, D.N.; Traber, D.L. Thomas Jefferson Medical College, Philadelphia, PA Westfaelian Wilhelms Univ., Muenster )

    1988-04-01

    A bolus of Escherichia coli endotoxin (1.5 {mu}g/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

  16. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

    NASA Technical Reports Server (NTRS)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

    1995-01-01

    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  17. Atrial natriuretic factor (ANF) inhibits thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B. )

    1990-01-01

    Recently, thyroid follicular cells were shown to exhibit atrial natriuretic factor (ANF)-like immunoreactivity and high affinity ANF receptors. In this study, we therefore examined the effects of synthetic rat ANF{sub 1-28} on basal and stimulated thyroid hormone secretion in the mouse, according to the McKenzie technique. Iodine deficient mice were pretreated with {sup 125}I and thyroxine. ANF (3 nmol/animal) was found to inhibit the increase in blood radioiodine levels that was induced by TSH or vasoactive intestinal polypeptide (VIP). Furthermore, ANF and norepinephrine additively inhibited the TSH-induced increase in blood radioiodine levels. It is concluded that ANF inhibits thyroid hormone secretion, which, therefore, might be locally regulated by intrathyroidal ANF.

  18. Presence of immunoreactive atrial natriuretic peptide in follicular fluid, ovary and ovarian perfusates

    SciTech Connect

    Kim, Suhn Hee; Cho, Kyung Woo; Seul, Kyung Hwan; Ryu, Hoon; Koh, Gou Young )

    1989-01-01

    Immunoreactive atrial natriuretic peptide (ir-ANP) was measured in the follicular fluid of pig ovarian follicle, and rabbit ovarian homogenates and perfusates using a specific radioimmunoassay (RIA). Serial dilution curves made with the extracts of follicular fluid, ovarian homogenates and perfusates using Sep-Pak C18 cartridges were parallel with the RIA standard curve. On gel filtration chromatography and reverse phase HPLC, all extracted materials showed high and low molecular weight forms of ir-ANP. The amount of ir-ANP in rabbit ovary was 40.7{plus minus}0.39 pg/mg and that in follicular fluid of pig ovarian follicle was 18.88{plus minus}2.49 pg/ml.

  19. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

    NASA Technical Reports Server (NTRS)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

    1995-01-01

    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  20. Interaction of atrial natriuretic peptide with its receptors in bovine lung membranes.

    PubMed

    Abe, T; Arakawa, Y; Rajasekaran, A K; Yu, T H; Wada, O

    1995-03-31

    In bovine lung membranes, atrial natriuretic peptide (ANP) showed temperature-dependent binding to guanylate cyclase-natriuretic peptide receptor (NPR-GC). Photoaffinity labeling of the receptors with 4-azidobenzoyl (AZB)-125I-ANP and competitive binding studies with 125I-ANP, ANP, and atriopeptin I (API) revealed that NPR-GC was detected as the predominant ANP-binding protein at 0 degrees C, whereas at 37 degrees C natriuretic peptide clearance receptor (NPR-C) was detected as the predominant protein. The ratio of NPR-GC and NPR-C was 89:11 at 0 degrees C for 40 min, respectively, whereas 6:94 at 37 degrees C. AZB-125I-ANP bound to NPR-GC dissociated from the binding site within 5 min at 37 degrees C but not at 0 degrees C, whereas ANP bound to NPR-C did not dissociate from the binding site at 0 and 37 degrees C. The dissociated AZB-125I-ANP rapidly rebound to NPR-GC at 37 degrees C but not to NPR-C, and the dissociated NPR-GC was capable of binding. Some AZB-125I-ANP was hydrolyzed by a membrane-bound proteinase(s). Phosphoramidon inhibited the hydrolysis of AZB-125I-ANP. Thus, the dissociated AZB-125I-ANP rebound to NPR-GC and NPR-C. These results suggest that usually intact ANP repeatedly binds to NPR-GC until hydrolysis. Furthermore, the majority of ANP bind to NPR-GC before binding to NPR-C under physiological temperature.

  1. Physiological factors of atrial natriuretic polypeptide release and its neural regulation in conscious dogs.

    PubMed

    Nishida, Y; Miyata, A; Morita, H; Hosomi, H

    1988-12-01

    We have examined physiological factors in atrial natriuretic polypeptide (ANP) release and whether or not the cardiac nerves control release of ANP. Two possible factors were tested, an increase in plasma sodium level (PNa) and an increase in atrial pressure. Injection of 1.0 or 2.0 mEq/kg of sodium ions elevated PNa by 5.3 +/- 0.3 or 7.3 +/- 0.4 mEq/L, respectively, but plasma ANP level (PANP) did not change. Infusion of 18 ml/kg of 3% Dextran-40 over 5 min increased mean left atrial pressure (MLAP) by 7.6 +/- 0.9 mmHg. PANP increased from 206 +/- 17 pg/ml to 260 +/- 25 pg/ml, which was not significant. PANP, corrected for hemodilution, significantly increased to 348 +/- 34 pg/ml. These results suggest that PNa increase does not promote ANP release, but that an atrial pressure increase does. This transient volume load did not induce full response of the ANP releasing system. A prolonged volume load for 45 min increased corrected PANP to 435 +/- 73 pg/ml. A close linear correlation was found between the increases in MLAP and PANP. These facts indicate that prolonged volume expansion is necessary to induce full response of the ANP releasing system. Complete cardiac denervation did not affect the tonic level of plasma ANP, volume expansion-induced increase in PANP, or the sensitivity of the ANP releasing system. Thus we conclude that the cardiac nerves do not control ANP release caused by volume expansion.

  2. Atrial natriuretic peptide modulates the proliferation of human gastric cancer cells via KCNQ1 expression

    PubMed Central

    ZHANG, JIA; ZHAO, ZHILONG; ZU, CHAO; HU, HAIJIAN; SHEN, HUI; ZHANG, MINGXIN; WANG, JIANSHENG

    2013-01-01

    Atrial natriuretic peptide (ANP) and brain NP (BNP) belong to the NP family that regulates mammalian blood volume and blood pressure. ANP signaling through NP receptor A (NPR-A)/cyclic guanosine 3′5′-monophosphate (cGMP)/ cGMP-dependent protein kinase (PKG) activates various downstream effectors involved in cell growth, apoptosis, proliferation and inflammation. Evidence has shown the critical role of plasma K+ channels in the regulation of tumor cell proliferation. However, the role of ANP in the proliferation of gastric cancer cells is not clear. In the present study, the expression of NPR-A in the human gastric cancer cell line, AGS, and the effect of ANP on the proliferation of AGS cells were investigated using western blotting, immunofluorescence, qPCR and patch clamp assays. The K+ current was also analyzed in the effect of ANP on the proliferation of AGS cells. NPR-A was expressed in the human gastric cancer AGS cell line. Lower concentrations of ANP promoted the proliferation of the AGS cells, although higher concentrations decreased their proliferation. Significant increases in the levels of cGMP activity were observed in the AGS cells treated with 10−10, 10−9 and 10−8 M ANP compared with the controls, but no significant differences were observed in the 10−7 and 10−6 M ANP groups. The patch clamp results showed that 10−9 M ANP significantly increased the tetraethylammonium (TEA)- and 293B-sensitive K+ current, while 10−6 M ANP significantly decreased the TEA- and 293B-sensitive K+ current. The results showed that 10−10 and 10−9 M ANP significantly upregulated the expression of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) at the protein and mRNA levels, although 10−7 and 10−6 M ANP significantly downregulated the expression of KCNQ1. The data indicated that lower and higher concentrations of ANP have opposite effects on the proliferation of AGS cells through cGMP-dependent or -independent pathways. KCNQ1

  3. Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle.

    PubMed

    Yasunari, K; Kohno, M; Murakawa, K; Yokokawa, K; Horio, T; Takeda, T

    1992-04-01

    At least two types of receptors for natriuretic peptides have been reported: biologically active receptors coupled with guanylate cyclase (atrial natriuretic peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To elucidate the role of protein kinase C (PKC) in the regulation of ANP-B receptors, vascular smooth muscle cells in culture were treated with phorbol ester. Incubation with receptor agonists and phorbol ester led to the desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor and downregulation of PKC by long-term incubation of cells with phorbol esters blocked the phorbol ester-induced desensitization of the ANP-B receptor response, they did not block the ANP-induced desensitization of the ANP-B receptor response. In addition, when desensitization by phorbol esters was observed, ANP was still capable of desensitization. These observations suggest that the mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and PKC-independent and mediated by phorbol esters and ANP, respectively.

  4. Binding and functional effects of atrial natriuretic factor in isolated rat kidney

    SciTech Connect

    Suzuki, M.; Almeida, F.A.; Nussenzveig, D.R.; Sawyer, D.; Maack, T. )

    1987-11-01

    A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with {sup 125}I-labeled and unlabeled ANF 1-28 to determine the following: (1) distribution, capacity (C{sub max}), and apparent affinity (S{sub 50}) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and (2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had >90% of total binding sites whereas papilla had <2% of total binding sites with a 10-fold lower apparent affinity than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrates that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone.

  5. Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart

    PubMed Central

    Gutkowska, Jolanta; Jankowski, Marek; Lambert, Chantal; Mukaddam-Daher, Suhayla; Zingg, Hans H.; McCann, Samuel M.

    1997-01-01

    Previous studies indicated that the central nervous system induces release of the cardiac hormone atrial natriuretic peptide (ANP) by release of oxytocin from the neurohypophysis. The presence of specific transcripts for the oxytocin receptor was demonstrated in all chambers of the heart by amplification of cDNA by the PCR using specific oligonucleotide primers. Oxytocin receptor mRNA content in the heart is 10 times lower than in the uterus of female rats. Oxytocin receptor transcripts were demonstrated by in situ hybridization in atrial and ventricular sections and confirmed by competitive binding assay using frozen heart sections. Perfusion of female rat hearts for 25 min with Krebs–Henseleit buffer resulted in nearly constant release of ANP. Addition of oxytocin (10−6 M) significantly stimulated ANP release, and an oxytocin receptor antagonist (10−7 and 10−6 M) caused dose-related inhibition of oxytocin-induced ANP release and in the last few minutes of perfusion decreased ANP release below that in control hearts, suggesting that intracardiac oxytocin stimulates ANP release. In contrast, brain natriuretic peptide release was unaltered by oxytocin. During perfusion, heart rate decreased gradually and it was further decreased significantly by oxytocin (10−6 M). This decrease was totally reversed by the oxytocin antagonist (10−6 M) indicating that oxytocin released ANP that directly slowed the heart, probably by release of cyclic GMP. The results indicate that oxytocin receptors mediate the action of oxytocin to release ANP, which slows the heart and reduces its force of contraction to produce a rapid reduction in circulating blood volume. PMID:9326674

  6. The effect of discrete stimulation of carotid body chemoreceptors on atrial natriuretic peptide in anaesthetized dogs.

    PubMed Central

    al-Obaidi, M; Whitaker, E M; Karim, F

    1991-01-01

    1. In seven chloralose-anaesthetized and artificially ventilated beagles, the carotid sinus regions were vascularly isolated and perfused with either arterial or mixed (arterial and venous) blood (PO2 46.4 +/- 1.5 mmHg, mean +/- S.E.M.) to stimulate the chemoreceptors at constant flow and pressure. Cervical vagosympathetic trunks were ligated in all dogs, and gallamine triethiodide (2.0 mg kg-1 h-1, I.V.) was given in five dogs. Right atrial pressure was measured in all dogs, and left atrial pressure in four dogs. Mean aortic pressure was held constant (91.0 +/- 3.0 mmHg) by means of a reservoir connected to the animal via the common carotid and femoral arteries. Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay and urinary sodium by flame photometry. 2. In seven dogs with mean carotid sinus pressure maintained at 96.0 +/- 4.3 mmHg, stimulation of the carotid chemoreceptors for 25 min produced significant increases in left atrial pressure of 41.2 +/- 3.3% (n = 4; P less than 0.005) from 5.4 +/- 0.6 cmH2O and of 30.9 +/- 4.5% (n = 7; P less than 0.002) in ANP from 31.6 +/- 2.1 pg ml-1. However, chemoreceptor stimulation produced significant decreases in urine flow rate of 26.1 +/- 1.9% (n = 9; P less than 0.001) from 0.29 +/- 0.03 ml min-1 (100 g kidney weight)-1 and sodium excretion of 29.0 +/- 2.3% (P less than 0.001) from 8.5 +/- 1.7 mumol min-1 (100 g kidney weight)-1 but right atrial pressure and heart rate did not change significantly. In three of the dogs, beta-adrenoceptor blockade by atenolol (2 mg kg-1, I.V.) greatly reduced the effects of chemoreceptor stimulation on plasma levels of ANP. 3. The results show, for the first time, that discrete stimulation of the carotid chemoreceptors caused an increase in plasma ANP levels, probably due to the reflex increase in atrial pressure that results from an inhibition of the cardiac sympathetic nerves, and an increase in venous return from a reduction of peripheral vascular capacitance. PMID

  7. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats

    PubMed Central

    Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-01-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways. PMID:26515144

  8. Blood levels and renal effects of atrial natriuretic peptide in normal man.

    PubMed Central

    Weidmann, P; Hasler, L; Gnädinger, M P; Lang, R E; Uehlinger, D E; Shaw, S; Rascher, W; Reubi, F C

    1986-01-01

    Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important

  9. Influence of storage conditions on in vitro stability of atrial natriuretic peptide and of anesthesia on plasma atrial natriuretic peptide concentration in cats.

    PubMed

    Heishima, Yasuhiro; Hori, Yasutomo; Chikazawa, Seishiro; Kanai, Kazutaka; Hoshi, Fumio; Itoh, Naoyuki

    2016-08-01

    OBJECTIVE To investigate the in vitro stability of atrial natriuretic peptide (ANP) in plasma samples under various storage conditions and the influence of anesthesia on plasma ANP concentration in cats. ANIMALS 1 cat with congestive heart failure and 5 healthy adult mixed-breed cats. PROCEDURES A plasma sample from the cat with heart failure was serially diluted, and dilutional parallelism of ANP concentration was evaluated. Plasma samples containing aprotinin or serum samples from the 5 healthy cats were kept at room temperature (27°C) for ≤ 12 hours. Plasma samples from the same healthy cats were stored at -70°, -20°, or 4°C for ≤ 14 days. Plasma samples were obtained from the healthy cats before and during isoflurane anesthesia. Plasma ANP concentrations were measured at a commercial laboratory by use of a human ANP chemiluminescence assay. RESULTS Intra- and interassay coefficients of variation were 1.5% and 2.5%, respectively, and dilutional parallelism was established. Although ANP concentration decreased by 82.4 ± 13.6% (mean ± SD) after sample storage for 12 hours at room temperature, this decrease was prevented by aprotinin. Plasma ANP concentrations were stable for 7 days at -20°C and for 14 days at -70°C. However, concentrations decreased markedly to 57.6 ± 6.9% at -20°C and to 18.0 ± 3.0% at 4°C after 14 days. Plasma ANP concentration decreased significantly in cats during anesthesia and was correlated with blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that aprotinin should be added routinely in preparation of plasma samples from cats for measurement of ANP concentration, and those samples, if stored, should be frozen immediately at ≤ -20°C. General anesthesia or systemic blood pressure may affect plasma ANP concentration in cats.

  10. Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

    SciTech Connect

    Gutkowska, J.; Horky, K.; Schiffrin, E.L.; Thibault, G.; Garcia, R.; De Lean, A.; Hamet, P.; Tremblay, J.; Anand-Srivastava, M.B.; Januszewicz, P.

    1986-06-01

    A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 ..mu..g ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.

  11. Atrial natriuretic factor in the impulse-conduction system of rat cardiac ventricles.

    PubMed

    Cantin, M; Thibault, G; Haile-Meskel, H; Ding, J; Milne, R W; Ballak, M; Charbonneau, C; Nemer, M; Drouin, J; Garcia, R

    1989-01-01

    A complex network of atrial natriuretic factor-producing cells has been delineated by biochemical and morphological techniques in the rat ventricular myocardium. The chordae tendineae spuriae (CTS; false tendons) contain ANF mRNA and the ANF propeptide (Asn 1-Tyr 126) as assessed by Northern blot analysis, high-pressure liquid chromatography and immunohisto- and -cytochemistry, using three different affinity-purified antibodies: monoclonal and polyclonal antibodies against C-terminal ANF (Arg 101-Tyr 126) and polyclonal antibodies against N-terminal ANF (Asp 11-Ala 37). Two types of cells harboring ANF-containing secretory granules constitute the CTS: the majority (Purkinje type I) have ultrastructural similarities with both atrial and classical Purkinje fibers. Purkinje type-II fibers resemble working ventricular cardiocytes. Both cell types harbor a large paranuclear Golgi complex. The subendocardial Purkinje network is also made up of these two cell types. In this location, Purkinje type-I fibers form cable-like structures while Purkinje type-II fibers are either located beneath the former or abut directly on the endocardium. The latter are not separated from adjacent working ventricular cardiocytes by connective tissue septa. Coronary arteries and arterioles, as in birds, are surrounded by a cushion of Purkinje type-II fibers which blend with the surrounding myocardium. These results indicate that, in the rat, the entire intraventricular conduction system is constituted of endocrine cells producing ANF.

  12. Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium.

    PubMed Central

    Kinnunen, P.; Taskinen, T.; Järvinen, M.; Ruskoaho, H.

    1991-01-01

    1. To determine the cellular mechanisms of atrial natriuretic peptide (ANP) release from ventricular cardiomyocytes, the secretory and the cardiac effects of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, were studied in isolated, perfused heart preparations from 2- and 21-month-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. TPA was added to the perfusion fluid for 30 min at a concentration of 46 nM after removal of atrial tissue. Additionally, atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP mRNA, the distribution of ANP within ventricles as well as the relative contribution of atria and ventricles in the release of ANP were studied. 2. Ventricular hypertrophy that gradually developed in hypertensive rats resulted in remarkable augmentation of ANP gene expression, as reflected by elevated levels of immunoreactive ANP and ANP mRNA. The total amount of IR-ANP in the ventricles of the SHR rats increased 41 fold and ANP mRNA levels 12.9 fold from the age of 2 to 21 months. At the age of 21 months, levels of IR-ANP and ANP mRNA in the ventricles of SHR rats were 5.4 fold and 3.7 fold higher, respectively, than in the normotensive WKY rats. Immunohistochemical studies demonstrated ANP granules within the hypertrophic ventricles of the old SHR rats, but not within normal ventricular tissue. 3. In isolated perfused heart preparations, the severely hypertrophied ventricular tissue of SHR rats after atrialectomy secreted more ANP into the perfusate than did the control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1826618

  13. Effects of atrial and brain natriuretic peptides upon cyclic GMP levels, potassium transport, and receptor binding in rat astrocytes

    SciTech Connect

    Beaumont, K.; Tan, P.K. )

    1990-02-01

    The ability of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) to alter cyclic GMP levels and NaKCl cotransport in rat neocortical astrocytes was determined. At concentrations of 10(-9)-10(-6) M, rat ANP99-126 (rANF), rat ANP102-126 (auriculin B), and rat ANP103-126 (atriopeptin III) stimulated 6- to 100-fold increases in cyclic GMP levels. Porcine BNP (pBNP) and rat BNP (rBNP) were 20%-90% as effective as rANF over most of this concentration range, although 10(-6) M pBNP produced a greater effect than rANF. NaKCl cotransport as measured by bumetanide-sensitive 86Rb+ influx was not altered by exposure of astrocytes to 10(-6)M rANF, pBNP, or rBNP. Both pBNP and rBNP, as well as rat ANP103-123 (atriopeptin I) and des(gl18, ser19, gly20, leu21, gly22) ANF4-23-NH2 (C-ANF4-23) strongly competed for specific 125I-rANF binding sites in astrocyte membranes with affinities ranging from 0.03 to 0.4 nM, suggesting that virtually all binding sites measured at subnanomolar concentrations of 125I-rANF were of the ANP-C (ANF-R2) receptor subtype. These receptors are thought to serve a clearance function and may be linked to a guanylate cyclase activity that is chemically and pharmacologically distinct from that coupled to ANP-A (ANF-R1) receptors. ANP receptors on astrocytes may function in limiting the access of ANP and BNP to neurons involved in body fluid and cardiovascular regulation.

  14. Plasmatic levels of N-terminal pro-atrial natriuretic peptide in preeclamptic patients and healthy normotensive pregnant women.

    PubMed

    Reyna-Villasmil, Eduardo; Mejia-Montilla, Jorly; Reyna-Villasmil, Nadia; Mayner-Tresol, Gabriel; Herrera-Moya, Pedro; Fernández-Ramírez, Andreina; Rondón-Tapía, Marta

    2017-08-31

    To compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. A cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. Plasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. Preeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  15. Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Whitson, P. A.

    1993-01-01

    Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

  16. Plasma concentrations of adrenomedullin and atrial and brain natriuretic peptides in patients with adrenal pheochromocytoma.

    PubMed

    Hu, Wei; Shi, Lei; Zhou, Pang-Hu; Zhang, Xiao-Bin

    2015-11-01

    The present study aimed to evaluate any changes in the plasma concentrations of adrenomedullin (ADM), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with adrenal pheochromocytoma (PC). The plasma concentrations of the three peptides were measured in 45 healthy control individuals and 90 untreated patients with PC, who consisted of 20 normotensive patients, 30 borderline hypertensive patients and 40 hypertensive patients. After 4 weeks of effective antihypertensive therapy for hypertensive PC patients, the concentrations of ADM, ANP and BNP were measured again, and laparoscopic adrenalectomy was then performed for all PC patients with values that were measured 2 weeks later. The plasma concentrations of the three peptides were significantly increased in the borderline hypertensive and hypertensive patients compared with the concentrations in control individuals and normotensive patients. In addition, there were significant differences between the levels of ADM, ANP and BNP in the borderline and hypertensive groups. The plasma ADM concentration was not associated with the blood urea nitrogen levels, serum creatinine levels or glomerular filtration rate, but was correlated with the serum epinephrine, serum norepinephrine and urine vanillylmandelic acid levels. In addition, the ADM concentration was associated with the systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and plasma concentrations of ANP and BNP in the hypertensive patients with PC. After 4 weeks of antihypertensive treatment, the values of the three peptides in the hypertensive patients with PC were not significantly changed. As expected, the values in borderline and hypertensive groups were significantly decreased 2 weeks subsequent to surgery, whereas there were no significant changes in the normotensive group. ADM may participate, along with ANP and BNP, in the mechanisms that counteract further elevation

  17. Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Whitson, P. A.

    1993-01-01

    Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

  18. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    SciTech Connect

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  19. The N-terminal and C-terminal portions of the atrial natriuretic factor prohormone increase during preeclampsia.

    PubMed

    Merkouris, R W; Miller, F C; Catanzarite, V; Quirk, J G; Rigg, L A; Vesely, D L

    1991-05-01

    The influence of preeclampsia on the circulating concentrations of the 28-amino-acid carboxy terminus (C-terminus) (i.e., atrial natriuretic factor) and the amino terminus (N-terminus) of the 126-amino-acid atrial natriuretic factor prohormone (pro ANF) was studied in the third trimester with the use of three specific radioimmunoassays that recognize: (1) atrial natriuretic factor (i.e., amino acids 99 to 126), (2) the whole 98-amino-acid N-terminus, and (3) amino acids 31 to 67 from the midportion of the N-terminus of the prohormone. The C-terminus was significantly increased (p less than 0.001) in the third trimester in women with preeclampsia, the mean +/- SEM of 15 subjects was 150 +/- 7 pg/ml versus 89 +/- 7 pg/ml in the third trimester in 12 women during normal pregnancies and 65 +/- 2 pg/ml in 19 healthy nonpregnant women. The whole 98-amino-acid N-terminus, likewise, was significantly increased (p less than 0.001) in women with preeclampsia to 4706 +/- 629 pg/ml versus 2160 +/- 79 pg/ml in women in the third trimester of normal pregnancies and versus the circulating concentration of 1847 +/- 127 pg/ml in healthy nonpregnant women. ProANF 31 to 67 mean circulating concentration in preeclampsia was 4638 +/- 725 pg/ml, which was also significantly (p less than 0.001) increased compared with its mean circulating concentration in the third trimester of normal pregnancy of 1758 +/- 83 pg/ml or that in healthy nonpregnant women (1400 +/- 105 pg/ml). The circulating concentrations of both the N-terminus and C-terminus of the atrial natriuretic factor prohormone decreased within 24 hours after delivery in contrast to a normal pregnancy in which they both increase post partum. These results indicate a marked difference in the metabolism of both the N-terminus and the C-terminus of the atrial natriuretic factor prohormone in women with preeclampsia versus that in women with normal pregnancies or that in healthy nonpregnant women.

  20. Pertussis toxin treatment does not block inhibition by atrial natriuretic factor of aldosterone secretion in cultured bovine zona glomerulosa cells

    SciTech Connect

    De Lean, A.; Cantin, M.

    1986-03-05

    The authors have previously reported that atrial natriuretic factor (ANF) potently inhibits PGE or forskolin-stimulation aldosterone secretion in bovine zona glomerulosa (ZG) by acting through specific high affinity receptors. In order to evaluate the functional role of the regulatory protein N/sub i/ and the inhibition of adenylate cyclase activity (AC) in ZG, the authors have studied the effect of treatment with PT on inhibition by ANF of aldosterone production. Primary cultures of ZG were treated for 18 hours in serum-free F12 medium with (0-100 ng/ml PT). No effect of PT pretreatment was observed either on basal, PGE-stimulated or ANF-inhibited levels of steroidogenesis. When membranes prepared from control ZG were ADP-ribosylated with (/sup 32/P) NAD in the presence of PT, two toxin-specific bands with 39 Kd and 41 Kd were documented on SDS gel. Cell pretreatment with as low as 1 ng/ml drastically reduced further labelling of these two bands while higher doses completely abolished them. Since PT treatment covalently modifies completely the toxin substrate without altering ANF inhibition of adrenal steroidogenesis, the authors conclude that N/sub i/ is not involved in the mode of action of ANF on aldosterone production.

  1. Characterization and purification of the detergent solubilized atrial natriuretic peptide receptor from bovine aortic smooth muscle cells

    SciTech Connect

    Schenk, D.; Phelps, M.; Scarborough, R.; Johnson, K.; Lewicki, J.

    1986-03-01

    A protein has been purified from total homogenates of cultured vascular bovine smooth muscle cells with properties indicative of the receptor for atrial natriuretic peptide (ANP). Specific /sup 125/I-ANP binding activity was solubilized quantitatively from smooth muscle cell membranes with a purified component of Triton X-100. Equilibrium binding studies of the solubilized ANP receptor reveal by Scatchard analysis a single class of binding sites with a K/sub d/ = 1.77 x 10/sup -10/ moles /sup 125/I-ANP/1 and B/sub max/ = 34.6 pmol/mg protein. The ANP receptor solubilized in this manner is stable for greater than or equal to 2 months at -70/sup 0/C. Studies investigating the ANP receptor show that it binds to wheat germ agglutinin and to CM-cellulose at pH 4.1 but not at pH 6.5. These findings imply that the ANP receptor is a neutral to mildly basic glycoprotein. Further purification studies involving affinity chromatography with ANP-Sepharose result in a 500-fold purification and reveal a single protein with a molecular mass of 58,700 daltons as determined by SDS-polyacrylamide gel electrophoresis. The size of this protein is in good agreement with that of an ANP receptor previously identified in intact smooth muscle cells by crosslinking studies with /sup 125/I-ANP.

  2. Changes in plasma atrial natriuretic peptide concentration in exercising horses in relation to hydration status and exercise intensity.

    PubMed

    Nyman, S; Kokkonen, U M; Dahlborn, K

    1998-04-01

    To investigate effects of hydration status and exercise intensity on plasma atrial natriuretic peptide (ANP) concentration in exercising horses. 4 trained Standardbreds. Horses performed a 40-minute exercise test at 65 to 70% maximal heart rate (HRmax; no incline) and a 12-minute test at approximately 90% HRmax (3.5 degrees incline). The 40-minute test was performed with ad libitum access to drinking water (normohydration), after water had been withheld for 24 hours (dehydration), and 30 minutes after 12 L of water at body temperature had been given via nasogastric tube (hyperhydration). The 12-minute test was only performed with normohydrated horses. Plasma ANP concentration was higher toward the end of exercise during hyperhydration than during the other 2 hydration states, and the area under the plasma ANP concentration curve was significantly greater during hyperhydration than during dehydration. The maximal plasma ANP value induced during the 12-minute test was similar to that of the 40-minute test. After the 12-minute test, plasma ANP concentration did not decrease during the first 30 minutes of recovery, whereas after the 40-minute test, plasma ANP concentration decreased by approximately 30% during the same period. Hydration status can affect plasma ANP concentration in horses during submaximal exercise. Maximal plasma ANP concentration was similar at the 2 exercise intensities studied, but the postexercise return to baseline values differed. Changes in hydration status can cause alterations in plasma concentration of ANP, one of the hormones involved in the control of cardiovascular functions during exercise.

  3. Cardiovascular effects of microinjection of atrial natriuretic factor (ANF) in the nucleus tractus solitarii of spontaneously hypertensive rats.

    PubMed

    Ermirio, R; Ruggeri, P; Cogo, C E; Picchio, V; Calaresu, F R

    1994-12-01

    The effects on mean arterial pressure (MAP) and heart rate (HR) of unilateral microinjections of atrial natriuretic factor (ANF) into discrete sites of the nucleus tractus solitarii (NTS) of spontaneously hypertensive rats (SHR) were compared with those observed in normotensive Wistar-Kyoto rats (WKY). NTS sites were identified to be involved in cardiovascular control on the basis of the bradycardia and hypotension elicited by microinjections of 20 nl of 0.1 M L-glutamate. Microinjection of 20 nl of 10(-7) M ANF into 38 NTS 'cardiovascular sites' in rats of the SHR strain decreased MAP (-8.7 +/- 1.8 mmHg) and HR (-7.8 +/- 1.9 bpm) in 9 sites (24%), but caused no changes in the remaining 29 sites (76%). In WKY rats 35 cardiovascular sites within the NTS were studied. In 18 sites (51%) ANF microinjections induced a decrease in MAP (-15.1 +/- 1.9 mmHg) and in HR (-18.1 +/- 3.9 bpm), whereas the remaining 17 sites (49%) were unaffected. The decreased responsiveness of the NTS to ANF in the SHR animals could play a role in the development and/or maintenance of the elevated arterial blood pressure in genetically hypertensive rats.

  4. Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

    PubMed Central

    Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

    1990-01-01

    1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

  5. Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure.

    PubMed

    Seta, K; Hayashi, T; Sugawara, A; Kasuno, K; Watanabe, S; Sumi, Y; Kijima, Y; Kawaguchi, K; Kotake, C; Seo, T; Toda, T; Kuwahara, T

    1998-09-01

    The present study was undertaken to verify the hypothesis that infusion of atrial natriuretic peptide (ANP) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22 patients with ARF secondary to CHF. The mean age of the patients (14 men and 8 women) was 72 years (range 36 to 85 years). Seven of the patients had dilated cardiomyopathy, ten had ischemic heart disease, and five had valvular heart disease. ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded; urinary output, systemic blood pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP), cardiac index (CI), heart rate (HR), and arterial blood oxygen partial pressure. Diastolic PBP were employed as pulmonary capillary wedge pressure. Urinary output did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m2 (p < 0.05). Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p < 0.05). In conclusion, ANP decreased preload and improved arterial blood oxygen partial pressure, though diuretic response to ANP is attenuated in ARF secondary to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems.

  6. Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat.

    PubMed

    Gauquelin, G; Bonhomme, M C; Garcia, R

    1995-03-01

    The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event. Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt. Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals. Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity.

  7. Atrial natriuretic peptide decreases blood volume in intact and anephric rats

    SciTech Connect

    Trippodo, N.C.; Chien, Y.W.; Pegram, B.L.; Cole, F.E.; MacPhee, A.A.; Kardon, M.B.

    1986-03-05

    Atrial natriuretic peptide (ANP) reportedly lowers atrial pressure and increases hematocrit, suggesting venodilation and/or decreased blood volume (BV). To examine these possibilities, rat ANP (99-126) was administered to Inactinanesthetized rats (313 +/- 9 g, +/- SE) at 0.5 ..mu..g/kg/min for 30 minutes. Urine flow increased by 0.05 ml/min (p < 0.001) during the last 15 minutes of infusion. Mean arterial pressure (MAP) and thoracic central venous pressure (CVP) decreased (p < 0.001) by 12 and 0.5 mmHg, respectively; hematocrit increased by 4.1 units (p < 0.001) and BV (/sup 51/Cr-RBC) decreased by 3.4 ml/kg (p < 0.001). Mean circulatory filling pressure, measured by inflating an intracardiac balloon to briefly stop the circulation, did not change. Distribution of BV between the thoracic and spanchnic organs (whole-animal freezing in liquid nitrogen) was not measurably altered. The results suggest that the decrease in CVP was related more to decreased BV than to venodilation. To investigate possible mechanisms for the decreased BV, the same dose of ANP was administered to anephric rats. MAP decreased by 8 mmHg (p < 0.001); hematocrit increased by 2.4 units (p < 0.001) and BV decreased by 1.7 ml/kg (p < 0.05). The results indicate that short-term administration of ANP decreases blood volume by causing intravascular fluid to shift into the interstitium as well as by inducing diuresis.

  8. Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

    PubMed

    Kitagawa, H; Kitoh, K; Inoue, H; Ohba, Y; Suzuki, F; Sasaki, Y

    2000-04-01

    Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

  9. Effects of posture and ageing on circulating atrial natriuretic peptide levels in man.

    PubMed

    Haller, B G; Züst, H; Shaw, S; Gnädinger, M P; Uehlinger, D E; Weidmann, P

    1987-10-01

    Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.

  10. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  11. Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

    PubMed

    Maeda, K; Tsutamoto, T; Wada, A; Mabuchi, N; Hayashi, M; Hisanaga, T; Kamijo, T; Kinoshita, M

    2000-08-01

    To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.

  12. Response of atrial natriuretic factor to acute extracellular fluid volume in patients with pheochromocytoma.

    PubMed

    Paniagua, R; Rodríguez, E; Amato, D; Sánchez, G; Ron, O; Rodríguez, F; Herrera-Acosta, J

    2000-01-01

    Patients with pheochromocytoma have been reported to show high plasmatic atrial natriuretic factor (ANF) levels. Its source may not be the atrium because blood volume, the most important physiological stimulus for ANF release, is usually reduced in these patients. To evaluate ANF secretion functional integrity, we studied three patients with pheochromocytoma before and after surgical removal of the tumor. Extracellular fluid (ECF) volume, plasmatic ANF levels, and plasmatic renin activity (PRA) were measured. ANF was measured before and after an acute saline load of 1.5L in 90 min. Before surgery, ECF volume was normal or reduced, and PRA was normal but decreased after the saline load. By contrast, ANF was elevated and did not change after the saline load. After surgery ANF decreased, ECF volume rose, and the saline load induced a significant increase of plasma ANF and reduction of PRA. ANF was present in significant amounts in tumoral tissue homogenates. These data suggest that the tumor was the source of ANF in these patients with pheochromocytoma because high levels of ANF, despite reduced or normal ECF volume, as well as unresponsiveness to acute saline infusion, were found before surgery with subsequent normalization after tumor removal.

  13. Effect of prolonged high salt intake on atrial natriuretic factor's kinetics in rats

    SciTech Connect

    Widimsky, J.; Debinski, W.; Kuchel, O.; Buu, N.T.; Du Souich, P. )

    1990-05-01

    Plasma atrial natriuretic factor (ANF) paradoxically decreases after 5 weeks (but not after 3 weeks) of 8% NaCl intake in normotensive rats. As this phenomenon remains unaccounted for by changes in ANF production, we studied the disappearance of ({sup 125}I)ANF(99-126) from the circulation as an alternative explanation of plasma ANF decline. Following 5 weeks (but not 3 weeks) of an 8% NaCl diet, plasma concentrations of ({sup 125}I)ANF were significantly decreased and metabolic clearance rate and volume of distribution were increased compared to control rats fed a 0.8% NaCl diet. By studying ({sup 125}I)ANF tissue uptake we noted significantly greater peptide uptake after 5 weeks (but not after 3 weeks) of high salt consumption in several tissues. We hypothesize that prolonged (at least 5 weeks) 8% NaCl ingestion increases the density and/or affinity of ANF binding sites. These changes may be responsible for the previously observed decline in plasma ANF concentrations after a prolonged high salt intake.

  14. Circadian variation of plasma atrial natriuretic peptide, cortisol and fluid balance in the goat.

    PubMed

    Kokkonen, U M; Riskilä, P; Roihankorpi, M T; Soveri, T

    2001-01-01

    Circadian variation of plasma atrial natriuretic peptide (ANP), cortisol and fluid balance was studied in ten adult female goats. The concentrations of plasma antidiuretic hormone (ADH), electrolytes, creatinine and total protein, as well as plasma and urine osmolalities and renal electrolyte excretion and clearances (Cosm, CH2O, Ccrea), were used to evaluate fluid balance. At 3-h intervals, urine was collected from five goats and venous blood samples from all ten goats. Urethral catheterization had no effect on the results. Besides the lower plasma creatinine level in the dark than in daylight, no other changes were observed in relation to luminousness. Plasma concentrations of ANP, ADH, total protein and K, urine flow rate and osmolality, urine concentrations of Na, K and creatinine, renal Na and K excretion, Cosm, CH2O and Ccrea, and haematocrit showed no circadian variation. Circadian variation was observed in plasma osmolality (P < 0.05) and the concentrations of Na (P < 0.05) and creatinine (P < 0.05), with achrophases around 16:00 hours and nadirs between 01:00 and 07:00 hours. Changes in osmolality and Na followed the feeding schedule. There was a small elevation in plasma cortisol levels in six goats after midnight, which may be the consequence of circadian rhythm. In conclusion, the results suggest that in plasma ANP no circadian rhythm exists.

  15. Studies of the penetration of the blood brain barrier by atrial natriuretic factor.

    PubMed

    Levin, E R; Frank, H J; Weber, M A; Ismail, M; Mills, S

    1987-09-30

    The atrial natriuretic factors (ANF) have been detected in various areas of the brain. To determine whether circulating blood borne ANF could contribute to the ANF content in the central nervous systems we examined the ability of ANF-99-126 or ANF-102-126 to penetrate the blood brain barrier. Carotid artery injections of [3H] inulin with [125I] ANF in anesthetized rabbits resulted in a comparably minimal brain uptake index (BUI) for each labeled substance as measured in cerebral cortex extracts. Injection of [3H] HOH and [125I] ANF resulted in a mean BUI in cortex of 4.9 +/- .6 (SEM)% for ANF relative to triated water; this low uptake was not significantly saturable. The BUI ratio for ANF/HOH in olfactory bulb was somewhat higher though still low, at 7.0 +/- 9%, possibly reflecting the high density of ANF receptors in this structure. Infusion of [125I] ANF into the carotid artery of anesthetized rabbits resulted in little radioactivity being detected in the cerebrospinal fluid. Infusion of unlabeled ANF, which raised plasma levels as high as 26.3 ng/ml, resulted in little change in CSF levels. Our results demonstrate that the uptake of ANF into the brain is minimal and supports the idea that local synthesis of ANF predominantly accounts for the brain pool of this peptide.

  16. Binding, internalization, and degradation of atrial natriuretic peptide in cultured vascular smooth muscle cells of rat

    SciTech Connect

    Hirata, Y.; Takata, S.; Tomita, M.; Takaichi, S.

    1985-11-15

    Binding, internalization, and degradation of /sup 125/I-labeled-rat atrial natriuretic peptide (rANP) were studied in cultured rat aortic vascular smooth muscle cells (VSMC). At 37 degrees C, /sup 125/I-labeled-rANP rapidly bound to VSMCs, but the cell-bound radioactivity rapidly decreased upon subsequent incubation, while the binding was slow at 4 degrees C, reaching to an apparent equilibrium after 6 hrs. The cell-bound /sup 125/I-labeled-rANP at 37 degrees C is rapidly dissociated from VSMC (t 1/2: approximately 40 min) with the appearance of degradaded product(s) of radioligand in the medium, whereas the degradation was minimal at 4 degrees C. This degradative process was blocked by inhibitors of metabolic energy production (azide, dinitrophenol), inhibitors of lysosomal cathepsins (leupeptin, pepstatin), and lysosomotropic agents (NH/sub 4/Cl, chloroquine, lidocaine, methylamine, dansylcadaverine), but not by inhibitors of serine or thiol proteases. /sup 125/I-labeled-rANP initially bound to the cell-surface was rapidly internalized, and delivered to lysosomal structures, which was confirmed by autoradiographic studies. These data indicate that rANP, after binding to the cell-surface receptors, is rapidly internalized into the cells through receptor-mediated endocytosis, and subsequently degradaded by lysosomal hydrolases.

  17. The role of atrial natriuretic peptide (ANP) in cold-induced diuresis (CID)

    SciTech Connect

    Agnew, J.W.; Freund, B.J.; DuBose, D.A.; McKay, J.M.; Hashiro, G.M. Tripler Army Medical Center, Honolulu, HI )

    1991-03-11

    The hormonal control of cold-induced diuresis (CID) remains unresolved. This study investigated the role of ANP, plasma vasopressin (AVP), and aldosterone (ALDO) on CID. Four semi-nude men participated in a 210 min exposure to 15C and 29C air, on separate days. These subjects drank 300 mL of water and had an intravenous saline drip throughout both exposures to replace blood and insensible fluid losses. CID was observed in 15C but not in the 29C experiment, as indicated by a greater urine output. In 15C, atrial natriuretic peptide (ANP) increased after 90 min by 41% and remained elevated for 2 h relative to 29C. No differences were observed in AVP between 15C and 29C. In the 15C versus the 29C experiment, ALDO was approximately 37% lower at the pre, 15 and 90 min time periods. Mean arterial blood pressure was generally greater but only significant at 60 min during the 15C versus the 29C experiment. Urinary NA{sup +} excretion was elevated in 15C relative to 29C while no difference in K{sup +} excretion was observed. Although pressure effects may contribute, the observed natriuresis in the absence of a kaliuresis in the cold suggests a physiological role of ANP in CID.

  18. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    SciTech Connect

    Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.

  19. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    SciTech Connect

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-19

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of (/sup 125/I)-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of (/sup 3/H)-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.

  20. In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging.

    PubMed

    Willenbrock, R; Lambert, R; Tremblay, J; Bavaria, G; Langlois, Y; Léveillé, J; Flanagan, R; Hamet, P

    1992-11-01

    We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible.

  1. Regulation of endothelial cell shape and monolayer permeability by atrial natriuretic peptide

    SciTech Connect

    Lofton-Day, C.E.

    1989-01-01

    Atrial natriuretic peptide (ANP), considered to be an important regulator of intravascular fluid volume, binds specifically to receptors on endothelial cells. In this study, the role of ANP-specific binding was investigated by examining the effect of ANP on the morphology and macromolecular permeability of monolayer cultures of bovine aortic endothelial cells. ANP alone had no observable effect on the monolayers. However, incubation of monolayers with ANP antagonized thrombin- or glucose oxidase-induced cell shape changes and intercellular gap formation. ANP pretreatment also opposed the effect of thrombin and glucose oxidase on actin filament distribution as observed by rhodamine-phalloidin staining and digital image analysis of F0actin staining. In addition, ANP reversed cell shape changes and cytoskeletal alterations induced by thrombin treatment but did not reverse alternations induced by glucose oxidase treatment. ANP significantly reduced increases in monolayer permeability to albumin resulting from thrombin or glucose oxidases treatment. Thrombin caused a 2-fold increase in monolayer permeability to {sup 125}I-labeled albumin, which was abolished by 10{sup {minus}8}-10{sup {minus}6}M ANP pretreatment. Glucose oxidase caused similar increases in permeability and was inhibited by ANP at slightly shorter time periods.

  2. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    SciTech Connect

    Leitman, D.C.

    1988-01-01

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP.

  3. Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

    PubMed

    Boeck, L; Eggimann, P; Smyrnios, N; Pargger, H; Thakkar, N; Siegemund, M; Marsch, S; Rakic, J; Tamm, M; Stolz, D

    2011-03-01

    Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

  4. Responses of plasma human atrial natriuretic factor to high intensity submaximal exercise in the heat.

    PubMed

    Kraemer, W J; Armstrong, L E; Hubbard, R W; Marchitelli, L J; Leva, N; Rock, P B; Dziados, J E

    1988-01-01

    No data exists regarding responses of human atrial natriuretic factor (ANF) to exercise in the heat. The purpose of this study was to examine the responses of plasma ANF to high intensity submaximal (71% +/- 0.9 VO2max) exercise in the heat over an eight day acclimation period. Fourteen healthy males volunteered to participate in the study. Subjects performed intermittent exercises on a treadmill (0% grade) during 50 min of each 100 min trial in an environmental chamber maintained at 41.2 +/- 0.5 degrees C, 39.0 +/- 1.7% relative humidity. Blood was obtained from an antecubital vein after standing 20 min in the heat prior to exercise, and immediately after exercise. Measures were compared on days 1, 4 and 8. ANF did not change pre- to post-exercise nor did it change over the eight day heat acclimation period despite other heat acclimation adaptations. Conversely, plasma aldosterone (ALDO), renin activity (PRA) and cortisol (COR) all increased (p less than 0.05) pre- to post-exercise on each day but again no changes were observed over the eight day period. These data support that ANF may not increase when ALDO and PRA increases are observed.

  5. Atrial natriuretic factor as marker of myocardial compromise in Chagas' disease.

    PubMed

    Puyó, Ana M; Scaglione, Jorge; Auger, Sergio; Cavallero, Susana; Donoso, Adriana S; Dupuy, Horacio A; Fernández, Belisario E

    2002-05-15

    This study investigated the evolution of plasma atrial natriuretic factor (ANF) in patients in different stages of Chagas' disease and analyzed its usefulness as prognostic factor of the development of myocardial compromise in asymptomatic chagasic patients. Chagas' disease, a determinant of heart failure, is caused by the parasite Trypanosoma cruzi. A total of 21 chagasic patients were studied: 9 in the asymptomatic stage, 6 with conduction defects (CD), and 6 with chronic heart failure (CHF); and 31 controls: 16 healthy, 6 with CD, and 9 with CHF. Plasma ANF radioimmunoassay (RIA) and complementary studies were performed twice for each patient, with an interval period of 12 months. First sample: chagasic patients showed higher ANF levels in the CHF group than in CD and asymptomatic subjects; second sample: the peptide levels were higher in CHF patients than in the asymptomatic group. In non-chagasic CHF patients, ANF levels were higher than in CD patients and controls in both samples. ANF levels were not able to differentiate chagasic asymptomatic and CD patients from healthy subjects and CD controls; meanwhile, chagasic CHF patients showed lower plasma ANF than their controls. Furthermore, ANF is a sensitive marker capable of detecting gradual impairments in cardiac function in all patients studied.

  6. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    SciTech Connect

    Chartier, L.; Schiffrin, E.L.

    1987-04-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC/sub 50/) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC/sub 50/. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated /sup 45/Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.

  7. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  8. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  9. Atrial natriuretic peptide (ANP)-granules in the guinea pig atrial and auricular cardiocytes: an immunocytochemical and ultrastructural morphometric comparative study.

    PubMed

    Gama, Eliane Florencio; de Carvalho, Claudio Antonio Ferraz; Liberti, Edson Aparecido; de Souza, Romeu Rodrigues

    2007-01-01

    The atrial natriuretic peptide (ANP) is a peptide hormone that is mainly produced in the cardiac atria, where it is stored within granules. It is known that the four regions of the atrial-auricular complex (two atria and two auricles) produce and store ANP in the granules. However, no report has been presented comparing the presence of ANP, and the number and diameter of atrial granules in the atria and auricles. ANP immunoreactivity was detected in cardiocytes from the four regions of the atrial-auricular complex. No differences were observed among the regions. The number of granules was greatest in the right atrium followed by the left atrium and left auricle and right auricle, in this order. The diameter of granules in the cardiocytes was significantly largest in the right atrium and reduced via the left auricle to the left atrium and right auricle. Both the number and diameter of the granules are larger in the right atrium in comparison with the other regions of the atrial-auricular complex, which leads to the supposition that this region is the one that most synthesizes and stores the ANP.

  10. Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure

    PubMed Central

    KANNO, Nobuyuki; HORI, Yasutomo; HIDAKA, Yuichi; CHIKAZAWA, Seishiro; KANAI, Kazutaka; HOSHI, Fumio; ITOH, Naoyuki

    2015-01-01

    The clinical utility of plasma natriuretic peptide concentrations in dogs with right-sided congestive heart failure (CHF) remains unclear. We investigated whether plasma levels of atrial natriuretic peptide (ANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are useful for assessing the congestive signs of right-sided heart failure in dogs. This retrospective study enrolled 16 healthy dogs and 51 untreated dogs with presence (n=28) or absence (n=23) of right-sided CHF. Medical records of physical examinations, thoracic radiography and echocardiography were reviewed. The plasma concentration of canine ANP was measured with a chemiluminescent enzyme immunoassay. Plasma NT-proBNP concentrations were determined using an enzyme immunoassay. Plasma ANP and NT-proBNP concentrations in dogs with right-sided CHF were significantly higher than in healthy controls and those without right-sided CHF. The plasma NT-proBNP concentration >3,003 pmol/l used to identify right-sided CHF had a sensitivity of 88.5% and specificity of 90.3%. An area under the ROC curve (AUC) was 0.93. The AUC for NT-proBNP was significantly higher than the AUCs for the cardiothoracic ratio, vertebral heart score, ratio of right ventricular end-diastolic internal diameter to body surface area, tricuspid late diastolic flow and ratio of the velocities of tricuspid early to late diastolic flow. These results suggest that plasma ANP and NT-proBNP concentrations increase markedly in dogs with right-sided CHF. Particularly, NT-proBNP is simple and helpful biomarkers to assess the right-sided CHF. PMID:26607133

  11. A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide

    PubMed Central

    Klaiber, Michael; Dankworth, Beatrice; Kruse, Martin; Hartmann, Michael; Nikolaev, Viacheslav O.; Yang, Ruey-Bing; Völker, Katharina; Gaßner, Birgit; Oberwinkler, Heike; Feil, Robert; Freichel, Marc; Groschner, Klaus; Skryabin, Boris V.; Frantz, Stefan; Birnbaumer, Lutz; Pongs, Olaf; Kuhn, Michaela

    2011-01-01

    Cardiac atrial natriuretic peptide (ANP) regulates arterial blood pressure, moderates cardiomyocyte growth, and stimulates angiogenesis and metabolism. ANP binds to the transmembrane guanylyl cyclase (GC) receptor, GC-A, to exert its diverse functions. This process involves a cGMP-dependent signaling pathway preventing pathological [Ca2+]i increases in myocytes. In chronic cardiac hypertrophy, however, ANP levels are markedly increased and GC-A/cGMP responses to ANP are blunted due to receptor desensitization. Here we show that, in this situation, ANP binding to GC-A stimulates a unique cGMP-independent signaling pathway in cardiac myocytes, resulting in pathologically elevated intracellular Ca2+ levels. This pathway involves the activation of Ca2+‐permeable transient receptor potential canonical 3/6 (TRPC3/C6) cation channels by GC-A, which forms a stable complex with TRPC3/C6 channels. Our results indicate that the resulting cation influx activates voltage-dependent L-type Ca2+ channels and ultimately increases myocyte Ca2+i levels. These observations reveal a dual role of the ANP/GC-A–signaling pathway in the regulation of cardiac myocyte Ca2+i homeostasis. Under physiological conditions, activation of a cGMP-dependent pathway moderates the Ca2+i-enhancing action of hypertrophic factors such as angiotensin II. By contrast, a cGMP-independent pathway predominates under pathophysiological conditions when GC-A is desensitized by high ANP levels. The concomitant rise in [Ca2+]i might increase the propensity to cardiac hypertrophy and arrhythmias. PMID:22027011

  12. Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet

    PubMed Central

    Della Penna, Silvana Lorena; Cao, Gabriel; Carranza, Andrea; Zotta, Elsa; Gorzalczany, Susana; Cerrudo, Carolina Susana; Rukavina Mikusic, Natalia Lucía; Correa, Alicia; Trida, Verónica; Toblli, Jorge Eduardo; Fernández, Belisario Enrique

    2014-01-01

    In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis. PMID:24689065

  13. Vagal reflex actions of atrial natriuretic peptide survive physiological but not pathological cardiac hypertrophy in rat.

    PubMed

    Hood, Sally G; Woods, Robyn L

    2004-07-01

    Atrial natriuretic peptide (ANP) enhances cardiac vagal baroreflexes in normotensive animals. In spontaneously hypertensive rats (SHRs) this effect of ANP was absent. The reflex actions of ANP were preserved if hypertrophy was completely prevented in SHRs. However even a small amount of cardiac hypertrophy, with no hypertension, in SHRs was accompanied by a loss of the reflex bradycardic actions of ANP. In the present study, we investigated whether pathophysiological cardiac hypertrophy, induced by one-kidney, one-clip renovascular hypertension (1K-1C; n = 6), or physiological cardiac hypertrophy induced by chronic spontaneous, wheel-running exercise training (n = 7), similarly prevented vagal reflex actions of ANP. Cardiac baroreceptor-activated bradycardia was measured during rapid ramp increases ( approximately 5 s) in blood pressure after bolus doses of methoxamine or vehicle in conscious, chronically instrumented rats during infusions of ANP (50 pmol kg(-1) min(-1)). Compared with uninephrectomised control rats (n = 10), rats with 1K-1C had cardiac hypertrophy (approximately 55% increase in left ventricle:body weight (LV:BW) ratio; P < 0.05) and blunted vagal baroreflex gain (-0.93 +/- 0.18 versus-0.50 +/- 0.13 beats min(-1) mmHg(-1); P < 0.05). ANP did not augment baroreflex function in 1K-1C. Compared with their sedentary controls (n = 7), exercise-trained rats with cardiac hypertrophy ( approximately 20% increase LV:BW ratio; P < 0.05) also had blunted ramp baroreflex bradycardia (-1.28 +/- 0.23 versus-0.57 +/- 0.09 beats min(-1) mmHg(-1); P < 0.05). In contrast, ANP more than doubled baroreflex bradycardia in exercise-trained rats (P < 0.05). The aetiology of cardiac hypertrophy therefore influenced whether ANP retained its vagal baroreflex enhancing properties. Copyright 2004 The Physiological Society

  14. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  15. Atrial natriuretic peptide protects against Staphylococcus aureus-induced lung injury and endothelial barrier dysfunction

    PubMed Central

    Xing, Junjie; Moldobaeva, Nurgul

    2011-01-01

    Lung inflammation and alterations in endothelial cell (EC) permeability are key events to development of acute lung injury (ALI). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and attenuate lung inflammation and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout mice (Nppa−/−) were treated with gram-positive bacterial cell wall compounds, Staphylococcus aureus-derived peptidoglycan (PepG) and/or lipoteichoic acid (LTA) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2 μg/kg). In vitro, human pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-κB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced lung inflammation and barrier dysfunction was further augmented in ANP−/− mice and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of ALI associated with gram-positive infection. Thus ANP may have important implications in therapeutic strategies aimed at the treatment of sepsis and ALI-induced gram-positive bacterial

  16. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides

    PubMed Central

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-01-01

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nm) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P= 0.01, n= 7) and 2.7 ± 0.8-fold (P= 0.07, n= 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P= 0.005) and frequency (P= 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion. PMID:23897233

  17. Clonidine stimulates atrial natriuretic factor (ANF) release in water-deprived rats.

    PubMed

    Baranowska, B; Tremblay, J; Gutkowska, J

    1988-01-01

    To determine the effect of clonidine, an alpha 2-adrenergic agonist, on atrial natriuretic factor (ANF) release during water deprivation, plasma immunoreactive ANF (IR-ANF) arginine vasopressin, diuresis and natriuresis were measured in rats which had been deprived of water for 24 and 48 hr after intravenous (IV) administration of 50 micrograms clonidine. In normally-hydrated rats clonidine produced a marked elevation of plasma IR-ANF from 40.5 +/- 4.6 pg/ml to 1064 +/- 22 pg/ml (mean +/- SEM) and sodium excretion from 73.3 +/- 6.8 microEq to 723.4 +/- 62.3 microEq. Clonidine evoked an increase in plasma IR-ANF from 16.6 +/- 5.9 pg/ml to 229.5 +/- 60 pg/ml (mean +/- SEM) after 24 hr water deprivation and from 13.6 +/- 7.4 pg/ml to 104.8 +/- 21 pg/ml (mean +/- SEM) after 48 hr water deprivation. Clonidine did not induce any significant changes in vasopressin levels. During 24 hr and 48 hr water deprivation vasopressin rose from 3.1 +/- 0.3 pg/ml to 7.3 +/- 1.3 pg/ml and 8.4 +/- 0.6 pg/ml (mean +/- SEM), respectively. In normally-hydrated rats clonidine produced a marked diuresis and natriuresis. These effects and urinary cGMP excretion were significantly inhibited by anti-ANF antibodies. Clonidine caused a significant increase in urine output in 24 hr water-deprived rats but the response was markedly lower than that seen in normally-hydrated rats. In conclusion, clonidine stimulates ANF release both in normally-hydrated and water-deprived rats. The diuretic effect of clonidine appears to be related to ANF release but not to inhibition of vasopressin.

  18. Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Costa, María A.; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analía L.

    2015-01-01

    Objective The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay. Results Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes. Conclusions Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes. PMID:25774801

  19. Thyrotropin modulates receptor-mediated processing of the atrial natriuretic peptide receptor in cultured thyroid cells

    SciTech Connect

    Tseng, Y.L.; Burman, K.D.; Lahiri, S.; Abdelrahim, M.M.; D'Avis, J.C.; Wartofsky, L. )

    1991-03-01

    In a prior study of atrial natriuretic peptide (ANP) binding to cultured thyroid cells, we reported that at 4 C, more than 95% of bound ANP is recovered on cell membranes, with negligible ANP internalization observed. Since ANP binding was inhibited by TSH, we have further studied TSH effects on postbinding ANP processing to determine whether this phenomenon reflects enhanced endocytosis of the ANP-receptor complex. An ANP chase study was initiated by binding (125I) ANP to thyroid cells at 4 C for 2 h, followed by incubation at 37 C. ANP processing was then traced by following 125I activity at various time intervals in three fractions: cell surface membranes, incubation medium, and inside the cells. Radioactivity released into medium represented processed ANP rather than ANP dissociated from surface membranes, since prebound (125I)ANP could not be competitively dissociated by a high concentration of ANP (1 mumol/L) at 37 C. Chase study results showed that prebound ANP quickly disappeared from cell membranes down to 34% by 30 min. Internalized ANP peaked at 10 min, with 21% of initial prebound ANP found inside the cells. At the same time, radioactivity recovered in incubation medium sharply increased between 10-30 min from 8% to 52%. Preincubation of cells with chloroquine (which blocks degradation of the ANP-receptor complex by inhibiting lysosomal hydrolase) caused a 146% increase in internalized (125I)ANP by 30 min (39% compared to 15% control), while medium radioactivity decreased from 52% to 16%, suggesting that processing of the receptor complex is mediated via lysosomal enzymes. In chase studies employing cells pretreated with chloroquine, TSH stimulated the internalization rate of ANP-receptor complex. By 30 min, TSH significantly reduced the membrane-bound ANP, and the decrease was inversely correlated to the increase in internalized radioactivity.

  20. Gene for the rat atrial natriuretic peptide is regulated by glucocorticoids in vitro.

    PubMed Central

    Gardner, D G; Gertz, B J; Deschepper, C F; Kim, D Y

    1988-01-01

    Glucocorticoids regulate the expression of the gene for atrial natriuretic peptide (ANP) in neonatal cardiocytes. Dexamethasone (Dex) increased cytoplasmic ANP mRNA levels and media ANP immunoreactivity in a dose-dependent fashion. These effects were not shared by the other classes of steroid hormones and were reversed by the glucocorticoid antagonist RU 38486. The effect on ANP mRNA levels resulted, at least in part, from enhanced transcription of the gene. Dex effected a two-fold increase in ANP gene activity assessed using a run-on transcription assay. The turnover of the ANP transcript was approximated using a standard pulse-chase technique. The half-life of the ANP mRNA was 18 h in hormone-free media. In the presence of Dex this half-life increased modestly to 30 h, although the increase relative to the control did not reach statistical significance. The effect of Dex at the level of the individual myocardial cell was assessed by in situ hybridization analysis using a specific [3H]cRNA probe. These studies demonstrated a significant level of ANP expression within a subpopulation of cells in the cultures. Exposure of the cells to Dex for 24 h did not recruit additional cells into the expressing pool (27.3% cells/high power field vs. 31.3% for the control) but did increase the level of expression (i.e., grain density) within individual cells. These findings indicate that glucocorticoids stimulate expression of the ANP gene directly at the level of the myocardial cell. This results predominantly from transcriptional activation in cells already expressing the gene rather than through recruitment of previously quiescent cells. Images PMID:2971674

  1. Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice.

    PubMed

    Werner, Franziska; Kojonazarov, Baktybek; Gaßner, Birgit; Abeßer, Marco; Schuh, Kai; Völker, Katharina; Baba, Hideo A; Dahal, Bhola K; Schermuly, Ralph T; Kuhn, Michaela

    2016-03-01

    The cardiac hormone atrial natriuretic peptide (ANP) regulates systemic and pulmonary arterial blood pressure by activation of its cyclic GMP-producing guanylyl cyclase-A (GC-A) receptor. In the lung, these hypotensive effects were mainly attributed to smooth muscle-mediated vasodilatation. It is unknown whether pulmonary endothelial cells participate in the homeostatic actions of ANP. Therefore, we analyzed GC-A/cGMP signalling in lung endothelial cells and the cause and functional impact of lung endothelial GC-A dysfunction. Western blot and cGMP determinations showed that cultured human and murine pulmonary endothelial cells exhibit prominent GC-A expression and activity which were markedly blunted by hypoxia, a condition known to trigger pulmonary hypertension (PH). To elucidate the consequences of impaired endothelial ANP signalling, we studied mice with genetic endothelial cell-restricted ablation of the GC-A receptor (EC GC-A KO). Notably, EC GC-A KO mice exhibit PH already under resting, normoxic conditions, with enhanced muscularization of small arteries and perivascular infiltration of inflammatory cells. These alterations were aggravated on exposure of mice to chronic hypoxia. Lung endothelial GC-A dysfunction was associated with enhanced expression of angiotensin converting enzyme (ACE) and increased pulmonary levels of Angiotensin II. Angiotensin II/AT1-blockade with losartan reversed pulmonary vascular remodelling and perivascular inflammation of EC GC-A KO mice, and prevented their increment by chronic hypoxia. This experimental study indicates that endothelial effects of ANP are critical to prevent pulmonary vascular remodelling and PH. Chronic endothelial ANP/GC-A dysfunction, e.g. provoked by hypoxia, is associated with activation of the ACE-angiotensin pathway in the lung and PH.

  2. Autoradiographic localization of atrial natriuretic peptide receptor subtypes in rat kidney

    SciTech Connect

    Brown, J.; Salas, S.P.; Singleton, A.; Polak, J.M. )

    1990-07-01

    The distribution of atrial natriuretic peptide (ANP) clearance receptors in rat kidney was investigated by in vitro autoradiography using des(Gln18,Ser19,Gly20,Leu21,Gly22)-ANP-(4- 23) (C-ANP) and 125I-Tyr0-ANP-(5-25) as relatively specific ligands of this receptor. Alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, outer medullary vasa recta bundles, and inner medulla. C-ANP (10 microM) inhibited greater than 60% of this glomerular binding but did not inhibit the binding of alpha-125I-ANP to medullary tissues. Alpha-125I-ANP also bound reversibly to the renal arteries up to the glomerulus. This arterial binding was only partly inhibited by 10 microM C-ANP. In the presence of 10 microM C-ANP, increasing concentrations of alpha-125I-ANP bound to a residue of glomerular sites with apparent dissociation constants of 0.82 +/- 0.16 to 2.73 +/- 1.20 nM at different cortical levels. 125I-Tyr0-ANP-(5-25) bound significantly to glomeruli and intrarenal arteries but not to vasa recta bundles or inner medulla. This glomerular binding also occurred with nanomolar dissociation constants. It was completely inhibited by 1 microM alpha-ANP and 10 microM C-ANP, but not by unrelated peptides such as gastrin. These results suggest that renal ANP clearance receptors are restricted in vivo to the glomeruli and renal arterial system of the rat.

  3. Synthesis, internalization, and localization of atrial natriuretic peptide in rat adrenal medulla

    SciTech Connect

    Morel, G.; Chabot, J.G.; Garcia-Caballero, T.; Gossard, F.; Dihl, F.; Belles-Isles, M.; Heisler, S.

    1988-07-01

    Some, though not all studies, have indicated that atrial natriuretic peptide (ANP) can bind to adrenal medullary cells. ANP-like immunoreactivity (ANP-LI) has also been identified in catecholamine-secreting cells. Together, these findings suggest that ANP may be taken up and/or synthesized in the adrenal medulla. The present study was designed to ascertain, by in situ hybridization, whether adrenal chromaffin cells could synthesize ANP, to define by an in vivo ultrastructural autoradiographic approach, whether ANP could, in fact, bind to rat adrenal medulla cells, to determine whether there was a cellular (noradrenaline (NA) vs. adrenaline (A)) selectivity in the binding process, and to establish whether extracellular (125I)ANP could be internalized by these cells. The cellular and subcellular distribution of endogenous ANP-LI was also investigated in both cell types by cryoultramicrotomy and immunocytochemical approaches. The in situ hybridization studies indicate the presence of mRNA to ANP in about 15% of adrenal medullary cells. Intravenous injection of (125I)ANP resulted in a 3-fold, preferential and specific radiolabeling of A-as compared to NA-containing cells. In A-containing cells, plasma membranes were significantly labeled 2 and 5 min post injection; cytoplasmic matrix, mitochondria, and secretory granules throughout the time course studied (1-30 min post injection). Lysosomes, rough endoplasmic reticulum, Golgi apparatus, and nuclei were not labeled. ANP-LI was identified in both NA- and A-containing cells; in the former, it was almost exclusively localized in secretory vesicles, in the latter it was detected in plasma membranes, cytoplasmic matrix, nuclear euchromatin, some mitochondria and relatively fewer granules than in NA-containing cells.

  4. The interaction of cadmium with atrial natriuretic factor: A study in in vivo and in vitro models

    SciTech Connect

    Giridhar, J.

    1990-01-01

    The involvement of atrial natriuretic factor (ANF) and its receptor in cadmium(Cd)-induced cardiovascular alterations and neurotoxicity is not known. This study examines the mechanisms underlying Cd-induced changes in the ANF peptide and its receptor in cardiovascular toxicity. In rats on short term Cd exposure (0.01, 0.1, 0.5 and 1.0 mg/kg, i.p., twice a day for 7 days and a maintenance period of 30 days), atrial ANF levels decreased significantly in the Cd 1 mg/kg group; plasma ANF levels were unchanged. Hypothalamic ANF content decreased significantly in 0.1-1.0 mg/kg Cd groups. Plasma renin activity and concentration were unchanged by Cd treatment. However, plasma aldosterone was significantly decreased in Cd 1.0 mg/kg group. Binding of [sup 125]I-ANF to its receptors in kidney, adrenals and aorta was not significantly altered. Cd treatment decreased urine volume indicating nephrotoxicity. Neuromodulation by ANF involved significant decrease in K[sup +] stimulated [[sup 3]H]NE release in rat hypothalamic slices. This action is proposed to be mediated by ANF-B receptors. 8Br-cGMP mimicked this action. In Cd treated animals (0.5 mg/kg twice a day for 7 days and maintained for 30 days), ANF neuromodulation in the hypothalmus was blocked, even though Cd content was undetectable. Cd preincubated (0.5 mM) slices showed a 49.1% block in neurotransmitter release indicating that Cd may block calcium channels leading to decreased K[sup +]-stimulated release of [[sup 3]H]NE. Hence, Cd-induced cardiovascular toxicity and neurotoxicity may be partly mediated by alteration in the release and possibly the synthesis of ANF peptide, disruption of ANF function through alterations in receptor dynamics and possibly alteration in cellular calcium homeostasis and membrane integrity. Central ANF function is sensitive to Cd and this effect may be partly resposible for the cardiovascular and neurotoxic responses to CD.

  5. Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

    PubMed Central

    Adnot, S; Andrivet, P; Chabrier, P E; Piquet, J; Plas, P; Braquet, P; Roudot-Thoraval, F; Brun-Buisson, C

    1989-01-01

    To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD. PMID:2522105

  6. The renal and vascular effects of central angiotensin II and atrial natriuretic factor in the anaesthetized rat.

    PubMed Central

    Al-Barazanji, K A; Balment, R J

    1990-01-01

    1. The interaction between atrial natriuretic factor (ANF) and angiotensin II (Ang II) within the brain to influence renal function and blood pressure was studied in Inactin-anaesthetized male Sprague-Dawley rats. 2. Central infusion of ANF produced a diuresis which was associated with a significant decrease in plasma arginine vasopressin (AVP) level. There was no change in sodium excretion rate over the 80 min of intracerebroventricular ANF infusion and ANF produced no detectable change in mean arterial blood pressure. 3. Central Ang II administration produced a significant decrease in urine flow, which was associated with elevated plasma AVP, an increase in sodium excretion and a rise in mean arterial blood pressure. 4. Combined ANF and Ang II infusion produced an antidiuresis, which was associated with increased plasma AVP concentration. Both the natriuretic and vasopressor actions of central Ang II were abolished when ANF was co-administered. 5. It is concluded that ANF and Ang II interact centrally; ANF antagonizes the pressor and natriuretic effects but not the antidiuretic effects of central Ang II. These data suggest the possibility of distinct and separate sites within the brain through which Ang II influences vasopressin release and renal sodium handling and elevates blood pressure. PMID:2143782

  7. Comparison of the effect of hypoxia on the secretion of the atrial natriuretic factor in spontaneously hypertensive and normotensive rats.

    PubMed

    Kovács, J; Behm, R; Gomba, S

    1991-01-01

    The effect of short lasting hypoxia on blood pressure, plasma atrial natriuretic peptide level and number of specific atrial granules were studied in 26 male spontaneously hypertensive and 24 normotensive Wistar rats. A great difference occurred in ANP secretion between hypertensive and normotensive rats. In the hypertensive animals elevated plasma ANP concentration (130 +/- 27 pg/ml) and decreased granularity in the right atria (73 +/- 2) were found on the first day of hypoxia with a slight elevation in urinary sodium content versus normotensive controls. The blood pressure also decreased although not significantly (190 +/- 14 mm Hg). In Wistar rats increased plasma ANP (130 +/- 34 pg/ml) and decreased atrial granularity versus normotensive controls (72 +/- 10 in the left and 113 +/- 16 in the right atrium) were observed only on the third day of hypoxia without changes in blood pressure and natriuresis. In SHR the rapid but short timed ANP release might be of right atrial origin and probably the consequence of a continuous and perhaps increased secretion of the peptide in normoxic conditions too. In Wistar rats the plasma ANP elevation could be secondary due to the increased plasma level of different vasoactive hormones to hypoxia. In the altered effect of ANP in hypertensive and normotensive hypoxic animals, structural and functional changes in the vascular bed may play a role.

  8. Atrial natriuretic peptide behaviour and myocyte hypertrophic profile in combined pressure and volume-induced cardiac hypertrophy.

    PubMed

    Cavallero, Susana; González, Germán E; Puyó, Ana M; Rosón, María I; Pérez, Susana; Morales, Celina; Hertig, Cecilia M; Gelpi, Ricardo J; Fernández, Belisario E

    2007-09-01

    To investigate cardiomyocyte hypertrophy and hormonal profile in cardiac hypertrophy resulting from sequentially applied overloads. We studied Sprague-Dawley rats with renovascular hypertension (RV), where pressure overload predominates, or deoxycorticosterone acetate (DOCA)-salt (DS), where volume overload predominates, at 2 and 4 weeks of treatment, and the combination of both models in inverse sequence: RV 2 weeks/DS 2 weeks (RV2/DS2) and DS 2 weeks/RV 2 weeks (DS2/RV2), and their sham controls (Sh). Blood pressure and cardiomyocyte diameter increased to a similar extent in RV and DS at 2 and 4 weeks and in combined models. Cardiomyocyte length increased remarkably in the DS4 group. Circulating atrial natriuretic peptide (ANP) was elevated in all hypertensive groups after 2 and 4 weeks. The RV2/DS2 group showed similar plasma ANP levels to RV4, but DS2/RV2 exhibited a three-fold increase in ANP levels (P<0.001 versus Sh4, DS2 and DS4). Atrial ANP mRNA remained unchanged in all groups. DS treatment alone or in combination with RV increased left ventricular ANP mRNA, meanwhile only RV treatment increased left ventricular B-type natriuretic peptide (BNP) mRNA. Ventricular ANP expression levels, but not circulating ANP, correlated with both cardiomyocyte diameter (r=0.859, P<0.01) and length (r=0.848, P<0.01). Renal expression of natriuretic peptide receptor C (NPR-C) was unchanged in RV4 but decreased to a similar extent in the DS4 group and both combined treatments. Morphometric patterns seem to be more related to the paracrine function of the heart than to the secretion of ANP and the endocrine function. Plasma ANP in the DS2/RV2 group could indicate a different evolution of the remodelling process. ANP expression seems to be a more sensitive marker for volume than for pressure overload.

  9. [High levels of atrial natriuretic peptide and copeptin and mortality risk].

    PubMed

    Rey, Corsino; García-Cendón, Clara; Martínez-Camblor, Pablo; López-Herce, Jesús; Concha-Torre, Andrés; Medina, Alberto; Vivanco-Allende, Ana; Mayordomo-Colunga, Juan

    2016-12-01

    To determine whether high levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin (PCT) plasma concentrations are associated with increased mortality risk. Prospective observational study including 254 critically ill children. MR-proANP, copeptin and PCT were compared between children with high (Group A; n=33) and low (Group B; n=221) mortality risk, and between patients with failure of more than 1 organ (Group 1; n=71) and less than 2 (Group 2; n=183). Median (range) of MR-proANP, copeptin, and PCT levels in group A vs B were, respectively: 209.4 (30.5-1415.8) vs. 75.0 (14.6-867.2) pmol/L (P<.001); 104.4 (7.4-460.9) vs. 26.6 (0.00-613.1) pmol/L (P<.001), and 7.8 (0.3-552.0) vs. 0.3 (0.02-107.0) ng/mL (P<.001). The area under the curve (AUC) for the differentiation of group A and B was 0.764 (95% CI: 0.674-0.854) for MR-proANP; 0.735 (0.642-0.827) for copeptin, and 0.842 (0.744-0.941) for PCT, with no statistical differences. The AUCs for the differentiation of group 1 and 2 were: 0.837 (0.784-0.891) for MR-proANP, 0.735 (0.666-0.804) for copeptin, and 0.804 (0.715-0.892) for PCT, with statistical differences between MR-proANP and copeptin, P=.01. High levels of MR-proANP, copeptin and PCT were associated with increased mortality risk scores. MR-proANP showed a higher association than copeptin with number of organs in failure. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. The effect of atrial natriuretic peptide infusion on intestinal injury in septic shock

    PubMed Central

    Elbaradey, Ghada F.; Elshmaa, Nagat Sayed; Hodeib, Hossam

    2016-01-01

    Background and Aims: The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock. Material and Methods: A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP. Results: In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125–130 mmol/L. Conclusion: In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect. PMID

  11. Homologous desensitization of guanylyl cyclase A, the receptor for atrial natriuretic peptide, is associated with a complex phosphorylation pattern

    PubMed Central

    Schröter, Juliane; Zahedi, René P; Hartmann, Michael; Gaßner, Birgit; Gazinski, Alexandra; Waschke, Jens; Sickmann, Albert; Kuhn, Michaela

    2010-01-01

    Atrial natriuretic peptide (ANP), via its guanylyl cyclase A (GC-A) receptor and intracellular guanosine 3′,5′-cyclic monophosphate production, is critically involved in the regulation of blood pressure. In patients with chronic heart failure, the plasma levels of ANP are increased, but the cardiovascular actions are severely blunted, indicating a receptor or postreceptor defect. Studies on metabolically labelled GC-A-overexpressing cells have indicated that GC-A is extensively phosphorylated, and that ANP-induced homologous desensitization of GC-A correlates with receptor dephosphorylation, a mechanism which might contribute to a loss of function in vivo. In this study, tandem MS analysis of the GC-A receptor, expressed in the human embryonic kidney cell line HEK293, revealed unambiguously that the intracellular domain of the receptor is phosphorylated at multiple residues: Ser487, Ser497, Thr500, Ser502, Ser506, Ser510 and Thr513. MS quantification based on multiple reaction monitoring demonstrated that ANP-provoked desensitization was accompanied by a complex pattern of receptor phosphorylation and dephosphorylation. The population of completely phosphorylated GC-A was diminished. However, intriguingly, the phosphorylation of GC-A at Ser487 was selectively enhanced after exposure to ANP. The functional relevance of this observation was analysed by site-directed mutagenesis. The substitution of Ser487 by glutamate (which mimics phosphorylation) blunted the activation of the GC-A receptor by ANP, but prevented further desensitization. Our data corroborate previous studies suggesting that the responsiveness of GC-A to ANP is regulated by phosphorylation. However, in addition to the dephosphorylation of the previously postulated sites (Ser497, Thr500, Ser502, Ser506, Ser510), homologous desensitization seems to involve the phosphorylation of GC-A at Ser487, a newly identified site of phosphorylation. The identification and further characterization of the

  12. Decreased atrial natriuretic factor receptors and impaired cGMP generation in glomeruli from the cardiomyopathic hamster.

    PubMed

    Levin, E R; Frank, H J; Chaudhari, A; Kirschenbaum, M A; Bandt, A; Mills, S

    1989-03-15

    To determine a possible basis for the decreased action of atrial natriuretic factors (ANF) in congestive heart failure, we compared the cardiomyopathic hamster (CMH) in frank congestive failure, and the age-matched, normal, F1B strain of Golden Syrian Hamsters. Scatchard analysis of competitive binding studies revealed two classes of glomerular receptors. The CMH exhibited decreased binding overall and a markedly decreased number of high affinity receptors but comparable receptor affinity compared to the F1B. In contrast, the low affinity receptor population in the CMH had a much greater affinity compared to the F1B while receptor number was similar. Plasma ANF levels were substantially elevated in the CMH compared to the F1B and in-vitro generation of cGMP was significantly lower in the CMH. Such abnormalities could contribute to the resistance to ANF in this disease.

  13. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  14. Increased atrial natriuretic peptide (6-33) binding sites in the subfornical organ of water deprived and Brattleboro rats

    SciTech Connect

    Saavedra, J.M.; Israel, A.; Correa, F.M.A.; Kurihara, M.

    1986-09-01

    Binding sites for rat atrial natriuretic eptide (6-33) (ANP) were quantitated in the subfornical organ of chronically dehydrated homozygous Brattleboro rats unable to synthesize vasopressin; heterozygous Brattleboro rats, their controls, Long Evans rats and Long Evans rats after 4 days of water deprivation. Brain sections were incubated in the presence of /sup 125/I-ANP and the results analyzed by autoradiography coupled to computerized microdensitometry and comparison to /sup 125/I-standards. Brattleboro rats and water deprived Long Evans rats presented a higher number of ANP binding sites than their normally hydrated controls. The results suggest a role of ANP binding sites in the subfornical organ in the central regulation of fluid balance and vasopressin secretion.

  15. Dehydration-induced changes in the secretion of atrial natriuretic factor in Brattleboro rats: effect of water-drinking.

    PubMed

    Januszewicz, P; Gutkowska, J; Thibault, G; Garcia, R; Mercure, C; Jolicoeur, F; Genest, J; Cantin, M

    1986-06-18

    The secretion of atrial natriuretic factor (ANF) was measured in Brattleboro rats (DI) subjected to 20-h dehydration and in normal Long-Evans rats (LE) subjected to 72-h dehydration and 7 times within the hour following voluntary rehydration by drinking water. In these rats, water deprivation caused a large, significant drop in plasma immunoreactive ANF (IR-ANF). Drinking water did not restore plasma IR-ANF values within one hour, even when indirect indices of intravascular volume such as serum osmolality, sodium and hematocrit returned to normal. The dehydration-induced decrease in plasma IR-ANF and its very low secretion after restoring drinking may be essential for the homeostasis of water conservation in both DI and LE rats.

  16. Expression of biologically active atrial natriuretic factor following intrahepatic injection of a replication-defective adenoviral vector in dogs.

    PubMed

    Chetboul, V; Adam, M; Deprez, I; Ambriovic, A; Rosenberg, D; Crespeau, F; Saana, M; Pham, I; Eloit, M; Adnot, S; Pouchelon, J L

    1999-01-20

    Atrial natriuretic factor (ANF) is a potent natriuretic, diuretic, and vasoactive hormone produced and released by atrial cardiomyocytes. We investigated whether adenovirus-mediated ANF gene delivery to dogs leads to a sustained increase in circulating ANF levels resulting in long-lasting biological effects. An adenoviral vector containing the canine ANF cDNA under the control of the Rous sarcoma virus 3' long terminal repeat (AdRSV-ANF) was injected via the intrahepatic route to nonvaccinated 2-month-old dogs. In the first group of four dogs injected with AdRSV-ANF (10(10.2) TCID50), a short-lived increase in plasma ANF concentrations not associated with biological effects occurred 8-10 days after the injection, as compared with four control dogs injected with an adenovirus encoding a luciferase reporter gene (AdRSV-luc). In a second series of experiments, six dogs received AdRSV-ANF at a dose of 10(10) TCID50 and a replication-defective type 5 adenovirus harboring a modified VAI gene (Ad-VAr) at the same dose. Sustained increases in plasma ANF concentrations and urinary cGMP excretion starting on day 2 and persisting until day 20 were seen, as well as concomitant elevations in natriuresis and diuresis, a transient increase in cardiac output, and a delay in body weight gain, as compared with control dogs injected with AdRSV-luc/Ad-VAr. These results show that adenovirus-mediated ANF gene expression can lead to systemic biological effects in dogs, a finding of potential relevance for the treatment of cardiovascular diseases and sodium-retaining disorders.

  17. Possible involvement of fibrocytes in atrial fibrosis in patients with chronic atrial fibrillation.

    PubMed

    Xie, Xudong; Liu, Yanrong; Gao, Shilong; Wu, Bifeng; Hu, Xiaosheng; Chen, Junzhu

    2014-01-01

    Chronic atrial fibrillation (AF) is characterized by a remodeling process with prominent atrial fibrosis. Fibrocytes, a bone marrow-derived population of fibroblast-like cells, have been placed at the center of a number of fibrosing conditions. The purpose of this study was to evaluate the contribution of fibrocytes to atrial fibrosis in patients with chronic AF and the possible mechanisms.  We enrolled 22 consecutive valvular heart disease patients with chronic AF (>6 months: CAF group) and 15 valvular heart disease patients in sinus rhythm served as controls (SR group). Left atrial tissue samples were obtained during cardiac surgery. The infiltration of fibrocytes into the atrial interstitium was observed by confocal microscopy. The number of atrial fibrocytes was approximately three-fold higher in the CAF group compared with the SR controls, and positively correlated with both the atrial collagen volume fraction (r=0.713; P=0.0002) and the left atrial volume index (r=0.631; P=0.002). In the peripheral blood samples collected before the operation, approximately 2.5-fold higher percentage of circulating fibrocytes was identified in the CAF group. These fibrocytes showed a stronger proliferative capacity (≍2.5-fold) and higher level expression of collagen I and α-SMA (≍2-fold and 4-fold, respectively) compared with the SR controls. The results suggested that fibrocytes may be involved in atrial fibrosis in chronic AF through enhanced profibrotic characteristics.  

  18. Association between left atrial appendage emptying velocity, N-terminal plasma brain natriuretic peptide levels, and recurrence of atrial fibrillation after catheter ablation.

    PubMed

    Ma, Xin-Xin; Zhang, Yue-Li; Hu, Bing; Jiang, Wen-Jun; Wang, Man; Zheng, Dong-Yan; Zhu, Meng-Ruo; Xue, Xiao-Pei

    2017-04-01

    Multiple studies have shown the efficacy and potentially curative effect of catheter ablation (CA). However, CA is always accompanied by a considerable recurrence rate for atrial fibrillation (AF). We hypothesized that pre-procedure assessments of baseline left atrial appendage emptying flow velocity (LAAFV) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels would help identify abnormal atrial substrate and offer preliminary evidence regarding susceptibility to AF recurrence in patients with paroxysmal or persistent AF, respectively. In 120 patients with AF (paroxysmal, 55; persistent, 65), transesophageal echocardiography was performed with assessment of LAAFV and NT-proBNP was measured before the first AF ablation. After 12 months of follow-up, 16 patients (29.1%) in the paroxysmal AF and 23 patients (35.4%) in the persistent AF experienced recurrence of AF. In ROC analysis, a NT-proBNP value of ≥291 pg/ml in the paroxysmal AF and ≥368 pg/ml in the persistent AF discriminated AFR and non-AFR with the greatest sensitivity and specificity. In multivariate regression analysis, LAAFV (OR 0.88, 95% CI 0.79-0.98, p = 0.023) was identified as an independent predictor of AFR in the paroxysmal AF population post-CA after adjustment for other risk factors; however, in the persistent AF population, LAAFV (OR 0.81, 95% CI 0.68-0.94, p = 0.007) and a NT-proBNP value ≥368 pg/ml (OR 18.29, 95% CI 1.32-252.84, p = 0.030) were identified as independent predictors for rhythm outcome compared to other parameters. In patients with persistent AF, elevated plasma NT-proBNP concentrations combined with low LAAFV were associated with rhythm outcome after AF ablation; however, LAAFV was the only independent predictor of CA efficacy in patients with paroxysmal AF.

  19. Plasma B-type natriuretic peptide levels and recurrent arrhythmia after successful ablation of lone atrial fibrillation.

    PubMed

    Hussein, Ayman A; Saliba, Walid I; Martin, David O; Shadman, Mazyar; Kanj, Mohamed; Bhargava, Mandeep; Dresing, Thomas; Chung, Mina; Callahan, Thomas; Baranowski, Bryan; Tchou, Patrick; Lindsay, Bruce D; Natale, Andrea; Wazni, Oussama M

    2011-05-17

    Plasma B-type natriuretic peptide (BNP) is abnormally elevated in patients with lone atrial fibrillation (AF). The exact significance and prognostic implications of this elevation have yet to be determined. Little is known about BNP in lone AF patients undergoing arrhythmia ablation. We sought to determine the relationship between BNP levels and the risk of recurrent arrhythmia after ablation of lone AF. We followed up 726 patients with lone AF undergoing first-time arrhythmia ablation. All had BNP levels measured on the day of ablation with of the point-of-care Triage Meter assay (Biosite Diagnostics, San Diego, CA). At baseline, factors associated with elevated BNP levels in multivariable linear regression analysis (with log BNP being the dependent variable) were older age (β regression coefficient for +1-year change, 0.025; P<0.0001), longer duration of AF (β for +1-year change, 0.031; P=0.01), nonparoxysmal AF (versus paroxysmal; β, 0.52; P<0.0001), and larger left atrial size (β for +1-cm(2) change, 0.040; P<0.0001). The BNP levels were strongly associated with arrhythmia recurrence in univariate- (hazard ratio for +1-log-BNP change, 2.32; 95% confidence interval, 2.11 to 2.74; P<0.001) and covariate- (hazard ratio for +1-log-BNP change, 2.13; 95% confidence interval, 2.06 to 2.38; P<0.001) adjusted Cox proportional hazards analysis. The covariate-adjusted hazard ratios for recurrent arrhythmia were 1.6, 2.7, 4.3, and 5.7 for the second, third, fourth, and fifth quintiles, respectively, compared with patients in the lowest quintile (P for trend across quintiles <0.001). B-type natriuretic peptide levels correlate with AF burden (chronicity, altered hemodynamics, and anatomic remodeling) in patients with lone AF and are strong predictors of recurrent arrhythmia after ablation. Elevated BNP levels may reflect increased cardiac chamber wall stress and/or intrinsic atrial disease, thus increasing the risk of arrhythmia recurrence.

  20. Irradiation-induced effects on mast cells, neuropeptides, and atrial natriuretic peptide in the rat heart and lung: bases for further studies.

    PubMed

    Forsgren, K S; Cavén, A G; Hansson, M C; Larsson, F H; Kjörell, U K; Henriksson, R G; Franzén, L I

    2001-01-01

    We examined the effects of irradiation over the thorax of the rat on the mast cells, the neuropeptide-containing nerve fibers, and the expression of atrial natriuretic peptide in the heart and lung. The total doses were 20 to 36 Gy delivered as single doses or fractionated irradiation. Immunohistochemical and radioimmunoassay methods were used. The number of mast cells was much reduced in both the lung and heart in response to irradiation. A trend for lowering the atrial natriuretic peptide levels in plasma was noted both 1 day and 9 days after irradiation. In contrast to the situation in other organs (salivary and laryngeal glands, the intestine), no changes occurred in the immunohistochemical expression of neuropeptides. With these observations and those made in previous studies about the effects of radiotherapy on other organs, the functional significance and basis for further research in the fields are discussed.

  1. Preoperative Echocardiographic Indices of Diastolic Dysfunction and Brain Natriuretic Peptide in Predicting Postoperative Atrial Fibrillation After Noncardiac Surgery.

    PubMed

    Brecher, Oren; Gulati, Harleena; Roistacher, Nancy; Zhang, Hao; Shi, Weiji; Thaler, Howard T; Amar, David

    2017-04-01

    We have shown previously that either echocardiographic indices of diastolic dysfunction or increased preoperative brain natriuretic peptide (BNP) predict postoperative atrial fibrillation (POAF). Because these 2 predictors of POAF have not been evaluated together, our goal was to further elucidate their concurrent role in patients undergoing noncardiac thoracic surgery. We retrospectively identified 191 patients who had a preoperative transthoracic echocardiogram and serum BNP level collected as part of routine care before major lung or esophageal resection. Clinical and echocardiographic data were compared between patients who did or did not develop POAF (>5 minutes), and prognostic factors for POAF were identified. Univariate associations with POAF (41 of 191; 22% patients) included older age (P = .04), male sex (P = .01), hypertension (P = .03), increased body mass index (P = .01), and prolonged transmitral flow deceleration time (P < .0001), whereas BNP was not statistically significant (P = .07). Stepwise logistic regression analysis showed that both increasing transmitral flow deceleration time (continuous data log base 2 transformed; odds ratio, 16.05; 95% confidence interval, 3.74-68.96; P = .0002) and left atrial diastolic volume index (continuous data log base 2 transformed; odds ratio, 3.29; 95% confidence interval, 1.22-8.91; P = .02) were independent risk factors of POAF (area under the receiver operating characteristic curve = 0.73). There was no significant interaction between BNP and the 2 independent variables (P = .60, and P = .90), respectively. In a cohort of patients who had echocardiography and BNP measurements before undergoing major thoracic surgery, this study showed that when evaluated together greater preoperative left atrial diastolic volume index and transmitral flow deceleration time but not BNP levels were independent predictors for POAF.

  2. A Constitutively “Phosphorylated” Guanylyl Cyclase-linked Atrial Natriuretic Peptide Receptor Mutant Is Resistant to Desensitization

    PubMed Central

    Potter, Lincoln R.; Hunter, Tony

    1999-01-01

    Dephosphorylation of the natriuretic peptide receptor-A (NPR-A) is hypothesized to mediate its desensitization in response to atrial natriuretic peptide (ANP) binding. Recently, we identified six phosphorylation sites within the kinase homology domain of NPR-A and determined that the conversion of these residues to alanine abolished the ability of the receptor to be phosphorylated or to be activated by ANP and ATP. In an attempt to generate a form of NPR-A that mimics a fully phosphorylated receptor but that is resistant to dephosphorylation, we engineered a receptor variant (NPR-A-6E) containing glutamate substitutions at all six phosphorylation sites. Consistent with the known ability of negatively charged glutamate residues to substitute functionally, in some cases, for phosphorylated residues, we found that NPR-A-6E was activated 10-fold by ANP and ATP. As determined by guanylyl cyclase assays, the hormone-stimulated activity of the wild-type receptor declined over time in membrane preparations in vitro, and this loss was blocked by the serine/threonine protein phosphatase inhibitor microcystin. In contrast, the activity of NPR-A-6E was more linear with time and was unaffected by microcystin. The nonhydrolyzable ATP analogue adenosine 5′-(β,γ-imino)-triphosphate was half as effective as ATP in stimulating the wild-type receptor but was equally as potent in stimulating NPR-A-6E, suggesting that ATP is required to keep the wild-type but not 6E variant phosphorylated. Finally, the desensitization of NPR-A-6E in whole cells was markedly blunted compared with that of the wild-type receptor, consistent with its inability to shed the negative charge from its kinase homology domain via dephosphorylation. These data provide the first direct test of the requirement for dephosphorylation in guanylyl cyclase desensitization and they indicate that it is an essential component of this process. PMID:10359598

  3. Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

    PubMed

    Wang, Dong; Gladysheva, Inna P; Fan, Tai-Hwang M; Sullivan, Ryan; Houng, Aiilyan K; Reed, Guy L

    2014-03-01

    Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

  4. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    PubMed Central

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  5. Role of atrial natriuretic peptide in mediating the blood pressure-independent natriuresis elicited by systemic inhibition of nitric oxide.

    PubMed

    Dobrowolski, Leszek; Kuczeriszka, Marta; Castillo, Alexander; Majid, Dewan S; Navar, L Gabriel

    2015-04-01

    While it is clearly recognized that increased intrarenal nitric oxide (NO) levels elicit natriuresis, confounding data showing that systemic nitric oxide synthase inhibition (NOSi) also increases sodium excretion (UNaV) poses a conundrum. This response has been attributed to the associated increases in arterial pressure (AP); however, the increases in AP and in UNaV are temporally dissociated. The changes in regional renal haemodynamics induced by NOSi could also contribute to the alterations of UNaV. To evaluate the roles of AP and non-AP mechanisms mediating the natriuresis, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) was infused i.v. at doses ranging from 5 to 50 μg/kg/min in anaesthetized rats. UNaV, perfusion of the cortex (cortical blood flow, CBF) and medulla (medullary blood flow, MBF) with laser-Doppler flowmetry and glomerular filtration rate (GFR) were measured. UNaV increased from 0.6 ± 0.2 to 1.6 ± 0.1 μmol/kg/min (P < 0.05) with the lower nonpressor doses. With the higher doses, AP increased from 116 ± 4 to 122 ± 4 mmHg and UNaV increased from 1.1 ± 0.3 to 3.3 ± 0.7 μmol/min/g (P < 0.002). UNaV increased similarly in a group where renal AP was maintained at baseline levels. The associated reductions in CBF (17 ± 5 and 38 ± 5 %) and MBF (27 ± 6 and 52 ± 6 %) would be expected to attenuate rather than contribute to the natriuresis. Plasma atrial natriuretic peptide (ANP) concentrations increased significantly following NOSi. Anantin, a natriuretic peptide receptor-A blocker, prevented or reversed the L-NAME-induced natriuresis without altering the L-NAME-induced changes in AP or CBF. The results indicate that increased ANP and related natriuretic peptides mediate the AP-independent natriuresis, at least partly, elicited by systemic L-NAME infusion and help resolve the conundrum of natriuresis during systemic NOSi.

  6. Synthetic atrial natriuretic peptide improves systemic and splanchnic circulation and has a lung-protective effect during endotoxemia in pigs.

    PubMed

    Sekino, Motohiro; Makita, Tetsuji; Ureshino, Hiroyuki; Sungsam, Cho; Sumikawa, Koji

    2010-01-01

    Pharmacological blockade of the renin-angiotensin system is thought to maintain gut perfusion during circulatory stress and thereby avoid later failure of distant organs. In this controlled experimental study, we investigated the effects of carperitide, a synthetic atrial natriuretic peptide that inhibits the renin-angiotensin system, on the systemic and splanchnic circulation during fluid-resuscitated endotoxemia in pigs. Sixteen domestic pigs of both sexes were randomly divided into 2 groups. The pigs were anesthetized and their lungs ventilated before receiving either saline (Group A: n = 8) or carperitide (Group B: n = 8). After a baseline measurement was taken, the pigs from both groups received a continuous infusion (1.7 microg x kg(-1) x h(-1)) of endotoxin for 240 min. Group B received a continuous infusion of carperitide (0.05 microg x kg(-1) x min(-1)) starting 30 min before the endotoxin infusion and lasting until the end of the study, whereas Group A received the same volume of saline. Fluid resuscitation was titrated to maintain pulmonary artery wedge pressure between 10 and 12 mm Hg. Systemic and regional hemodynamics, oxygenation variables, and the arterial-to-intestinal PCO(2) gap were measured at baseline and after endotoxin infusion for 240 min. The primary end points were cardiac index, superior mesenteric artery flow index, and PCO(2) gap at the end of this study (T240). Cardiac index and superior mesenteric artery flow index in Group B were significantly higher than those in Group A at T240 (83 +/- 15 vs 135 +/- 23 mL x kg(-1) x min(-1), P < 0.001; 2.6 +/- 1.4 vs 7.9 +/- 4.8, P = 0.01), respectively. Carperitide administration resulted in a significantly better maintenance of intestinal mucosal perfusion assessed by the PCO(2) gap at T240 (33.0 +/- 14.5 vs 11.6 +/- 10.0 mm Hg, P = 0.004). The PaO(2)/FIO(2) ratio in Group B was significantly greater than that in Group A from T60 to T240. In this porcine fluid-resuscitated endotoxemia model, a

  7. A combination of P wave electrocardiography and plasma brain natriuretic peptide level for predicting the progression to persistent atrial fibrillation: comparisons of sympathetic activity and left atrial size.

    PubMed

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Miyoshi, Fumito; Li, Hui-Ling; Watanabe, Norikazu; Asano, Taku; Tanno, Kaoru; Suyama, Jumpei; Namiki, Atsuo; Gokan, Takehiko; Kobayashi, Youichi

    2013-11-01

    Development of atrial fibrillation (AF) is complexly associated with electrical and structural remodeling and other factors every stage of AF development. We hypothesized that P wave electrocardiography with an elevated brain natriuretic peptide (BNP) level would be associated with the progression to persistence from paroxysmal AF. P wave electrocardiography such as a maximum P wave duration (MPWD) and dispersion by 12-leads ECG, heart/mediastinum (H/M) ratio by delayed iodine-123 metaiodobenzylguanidine scintigraphic imaging, left ventricular ejection fraction (LVEF), and left atrial dimension (LAD) by echocardiography, and plasma BNP level were measured to evaluate the electrical and structural properties and sympathetic activity in 71 patients (mean ± standard deviation, age: 67 ± 13 years, 63.4 % males) with idiopathic paroxysmal AF. Over a 12.9-year follow-up period, AF developed into persistent AF in 30 patients. A wider MPWD (>129 ms) (p = 0.001), wider P wave dispersion (>60 ms) (p = 0.001), LAD enlargement (>40 mm) (p = 0.001), higher BNP level (>72 pg/mL) (p = 0.002), lower H/M ratio (≤2.7) (p = 0.025), and lower LVEF (≤60 %) (p = 0.035) were associated with the progression to persistent AF, and the wide MPWD was an independently powerful predictor of the progression to persistent AF with a hazard ratio (HR) of 5.49 [95 % confidence interval (CI) 2.38-12.7, p < 0.0001] after adjusting for potential confounding variables, such as age and sex. The combination of wide MPWD and elevated BNP level was additive and incremental prognostic power with 13.3 [2.16-13, p < 0.0001]. The wide MPWD with elevated BNP level was associated with the progression to persistent AF.

  8. Clearance and early hydrolysis of atrial natriuretic factor in vivo. Structural analysis of cleavage sites and design of an analogue that inhibits hormone cleavage.

    PubMed Central

    Condra, C L; Leidy, E A; Bunting, P; Colton, C D; Nutt, R F; Rosenblatt, M; Jacobs, J W

    1988-01-01

    This study examines the clearance and early hydrolysis of atrial natriuretic factor (ANF) in vivo. Radiolabeled ANF was cleared from the circulation of the rat with biphasic kinetics; the majority (90%) of ANF cleared with a t1/2 of 15 s, the remaining peptide was cleared with a t1/2 of 5 min. Microsequence analysis of ANF peptides recovered from the circulation of rats revealed five major degradation products of the intact hormone. The first cleavage occurred between amino acids 12 and 13 of the hormone and would inactivate ANF. Over time, additional fragments of the hormone were generated, including fragments of 6, 7, 21, and 24 amino acids in length. Whole body radioautography of rats injected with [123I]-ANF revealed the kidney as a predominant organ involved in clearance of ANF. Subsequent amino acid sequence analyses of radiolabeled ANF exposed to the kidney in vivo indicated that this organ generated four of the five major hydrolysis products observed in circulation, namely, the 6, 7, 16, and 21 amino acid fragments of the hormone. In an attempt to stabilize ANF in vivo, a synthetic analogue of the hormone was prepared that contained the amino acid analogue, aminoisobutyric acid, substituted at position 13. This analogue completely abolished the in vivo cleavage of ANF at this site. These studies demonstrate the usefulness of a protein chemistry approach in characterizing hormone metabolism in vivo and designing analogues with enhanced in vivo stability to cleavage. Images PMID:2966813

  9. Atrial natriuretic peptide in the locus coeruleus and its possible role in the regulation of arterial blood pressure, fluid and electrolyte homeostasis

    SciTech Connect

    Geiger, H.; Sterzel, R.B. ); Bahner, U.; Heidland, A. ); Palkovits, M. )

    1991-01-01

    Atrial natriuretic factor (ANP) is present in neuronal cells of the locus coeruleus and its vicinity in the pontine tegmentum and moderate amount of ANP is detectable in this area by radioimmunoassay. The ANP is known as a neuropeptide which may influence the body salt and water homeostasis and blood pressure by targeting both central and peripheral regulatory mechanisms. Whether this pontine ANP cell group is involved in any of these regulatory mechanisms, the effect of various types of hypertension and experimental alterations in the salt and water balance on ANP levels was measured by radioimmunoassay in the locus coeruleus of rats. Adrenalectomy, as well as aldosterone and dexamethasone treatments failed to alter ANP levels in the locus coeruleus. Reduced ANP levels were measured in spontaneously hypertensive rats, and in diabetes insipidus rats with vasopressin replacement. In contrast to these situations, elevated ANP levels were found in rats with DOCA-salt or 1-Kidney-1-clip hypertension. These data suggest a link between ANP levels in the locus coeruleus and fluid volume homeostasis. Whether this link is causal and connected with the major activity of locus coeruleus neurons needs further information.

  10. Evaluation of plasma C-terminal atrial natriuretic peptide in healthy cats and cats with heart disease.

    PubMed

    Hori, Y; Yamano, S; Iwanaga, K; Kano, T; Tanabe, M; Uechi, M; Kanai, K; Nakao, R; Hoshi, F; Higuchi, S

    2008-01-01

    The clinical implications of evaluating C-terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial. The objective of this study was to investigate the relationship between plasma C-terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C-terminal ANP in normal cats and cats with cardiomyopathy (study 2). Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2. In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10-min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C-terminal ANP concentration was determined by radioimmunoassay for human alpha-ANP. In study 1, volume overload significantly increased the C-terminal ANP concentration and LAP from baseline. The C-terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C-terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats. Our results suggest that the measurement of plasma C-terminal ANP in cats may provide additional information for the diagnosis of heart disease.

  11. NMR study of the solution conformation of rat atrial natriuretic factor 7-23 in sodium dodecyl sulfate micelles

    SciTech Connect

    Olejniczak, E.T.; Gampe, R.T. Jr.; Rockway, T.W.; Fesik, S.W.

    1988-09-06

    The conformation of the cyclic portion (7-23) of naturally occurring rat atrial natriuretic factor, ANF(1-28), has been examined in sodium dodecyl sulfate (SDS) micelles using high-resolution NMR techniques. Evidence is presented which shows that ANF(7-23) has several regions of definable structure in SDS micelles which were not observed in earlier studies in bulk solvents. The /sup 1/H NMR resonances of ANF(7-23) in SDS micelles were assigned using sequential assignment techniques, and the conformational properties were analyzed primarily from proton-proton distances obtained from the quantitative analysis of two-dimensional nuclear Overhauser effect spectra. Three-dimensional structures consistent with the NMR data were generated by using distance geometry and constrained minimization/dynamics. Several similar but not identical structures were found which adequately satisfied the NMR constraints. Although none of the structures adopted a standard secondary structure, the conformations of three different sections of the peptide, 8-13, 14-17, and 18-21, were nearly identical in all of the predicted structures when individually superimposed.

  12. Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Chen, Y. M.; Whitson, P. A.

    1992-01-01

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  13. Salt-losing nephropathy associated with inappropriate secretion of atrial natriuretic peptide--a new clinical syndrome.

    PubMed

    Rodríguez-Soriano, J; Vallo, A

    1997-10-01

    A state of normokalemic renal sodium wasting associated with an apparently inappropriate secretion of atrial natriuretic peptide (ANP) has not been previously recognized. We here report an 11-year-old boy who presented with a chronic "salt-losing" nephropathy manifested by normonatremic or mildly hyponatremic extracellular fluid volume depletion, hypodipsia, absence of salt appetite, normokalemic metabolic alkalosis, hyper-reninemic hyperaldosteronism, hypertrophy of the juxtaglomerular apparatus, and highly conserved capacities for concentrating diluting the urine. Plasma ANP values were paradoxically elevated (between 10 and 47 fmol/ml), despite the coexistence of intravascular volume depletion and increased plasma levels of renin and aldosterone. Although the patient had some clinical similarities to Bartter's syndrome, fractional sodium chloride (NaCl) reabsorption during hypotonic saline diuresis was normal and no clinical amelioration was observed while on indomethacin therapy. Neither a tumor nor cardiac or cerebral abnormalities, which could be responsible for the increased ANP secretion, were detected. These clinical, biochemical, and histological features have not been previously described together and may represent a new clinical syndrome. The pathophysiology of this entity remains unknown, but an attractive, although unproven, hypothesis is that the renal defect in NaCl reabsorption in this patient could be related to an inappropriate and unregulated secretion of ANP.

  14. Sensitive radioimmunoassay of. cap alpha. human atrial natriuretic polypeptide using monoclonal antibody recognizing human form ring structure

    SciTech Connect

    Naomi, S.; Umeda, T.; Iwaoka, T.; Miura, F.; Ohno, M.; Sasaki, M.; Oishi, S.; Sato, T.; Takatsu, K.

    1988-01-01

    A monoclonal antibody (C351) against ..cap alpha.. human atrial natriuretic polypeptide (..cap alpha..hANP) recognizing human form ring structure was established and applied to a radioimmunoassay of plasma ..cap alpha..hANP. The minimum detectable amount in terms of 10 % radioligand displacement relative to zero dose were 0.28 fmol/tube, corresponding to 0.7 fmol/ml in plasma after extraction using Sep-Pak C18 cartridges. When the mean plasma levels at recumbent position in fasted morning were compared in 10 young (<30 years) and 10 elderly (greater than or equal to50 years) healthy subjects taking normal sodium diet, it was slightly higher in the latter. After i.v. infusion of hypertonic saline at a rate of 0.24 ml/kg/min for 20 min in 6 normal subjects (26 to 35 years), it was increased from 4.1 +/- 0.4 to 5.9 +/- 0.7 fmol/ml (p<0.01). In 6 patients with essential hypertension (34 to 57 years), it was elevated with high salt intake. From these results, the radioimmunoassay of plasma IR-..cap alpha..hANP using MAb C351 seems to be quite suitable to detect rather small changes at low plasma concentrations and to investigate a physiological importance of ..cap alpha..hANP in man.

  15. Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Chen, Y. M.; Whitson, P. A.

    1992-01-01

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  16. An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes.

    PubMed

    Ruiz-Ojeda, Francisco Javier; Aguilera, Concepción María; Rupérez, Azahara Iris; Gil, Ángel; Gomez-Llorente, Carolina

    2016-08-15

    The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases.

  17. Receptors for atrial natriuretic peptide (ANP) and regulation of thyroglobulin secretion by ANP in human thyroid cells

    SciTech Connect

    Sellitti, D.F.; Tseng, Y.C.L.; Wartofsky, L. Walter Reed Army Medical Center, Washington, DC )

    1989-01-01

    Specific binding sites for atrial natriuretic peptide (ANP) were identified and characterized in primary cultures of human thyroid cells. Saturation analysis using ({sup 125}I) {alpha} rat (1-28) ANP as the ligand showed a single class of high affinity binding which was inhibited by atriopeptin I and the {alpha} -human form of ANP, but not by a C-terminal fragment (13-28) of the peptide. The number of ANP binding sites in these cultures was not altered by the thyroid hormone concentration of the medium. In a dose-response experiment, thyroglobulin secretion was significantly reduced in the presence of 0.01 nM ANP and was maximally reduced with 10 nM ANP. Cyclic GMP production was increased threefold in the presence of 100 nM ANP, but was unchanged with lower doses of the peptides. The finding of receptors in thyroid follicular cells suggests a hitherto unrecognized role of ANP in the thyroid gland.

  18. Development and validation of a two-site immunoradiometric assay for human atrial natriuretic factor in unextracted plasma

    SciTech Connect

    Lewis, H.M.; Ratcliffe, W.A.; Stott, R.A.; Wilkins, M.R.; Baylis, P.H.

    1989-06-01

    This two-site immunoradiometric assay (IRMA) for human atrial natriuretic factor (ANF)99-126 in plasma utilizes a mouse monoclonal antibody raised against rat (r) ANF103-125 with specificity directed towards the ring structure of ANF, and a rabbit antiserum to human (h) ANF99-126. The monoclonal antibody is radioiodinated, and the IgG fraction of the antiserum is coated onto wells of a microtiter plate. Plasma or standard hANF99-126 (150 microL) is incubated with the radioligand in coated wells for 24 h. The detection limit is 0.9 pg per well, corresponding to 2 pmol/L, with a working range (CV less than 10%) from 4.5 to 540 pmol/L. Intra- and interassay precision are 7% and 9%, respectively, and the assay is unaffected by plasma matrix. In humans, the IRMA is specific for hANF99-126, the major circulating form of ANF, and does not cross-react with metabolites having deletions at the carboxy terminus. Plasma IRMA values in normal seated subjects were 6.6 +/- 1.5 (SEM) pmol/L and results correlated with those of an extraction RIA (r = 0.81, P less than 0.001).

  19. Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Yancy, Clyde W.; Buckey, Jay C.; Lane, Lynda D.; Hargens, Alan R.; Blomqvist, C. G.

    1992-01-01

    A hypothesis is proposed that a temporal relationship exists between increases in cardiac filling pressure and plasma artrial natriuretic peptide (ANP) concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). To test the hypothesis, 30 ml/kg isotonic saline were infused in supine male subjects over 24 min and responses were monitored for 3 h postinfusion. Results show that at end infusion, mean arterial pressure (RAP), heart rate and plasma volume exhibited peak increases of 146, 23, and 27 percent, respectively. Mean plasma ANP and UV peaked (45 and 390 percent, respectively) at 30 min postinfusion. Most cardiovascular variables had returned toward control levels by 1 h postinfusion, and net reabsorption of extravascular fluid ensued. It is concluded that since ANP was not significantly increased until 30 min postinfusion, factors other than ANP initiate responses to intravascular fluid loading. These factors include increased vascular pressures, baroreceptor-mediated vasolidation, and hemodilution of plasma proteins. ANP is suggested to mediate, in part, the renal response to saline infusion.

  20. Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Yancy, Clyde W.; Buckey, Jay C.; Lane, Lynda D.; Hargens, Alan R.; Blomqvist, C. G.

    1992-01-01

    A hypothesis is proposed that a temporal relationship exists between increases in cardiac filling pressure and plasma artrial natriuretic peptide (ANP) concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). To test the hypothesis, 30 ml/kg isotonic saline were infused in supine male subjects over 24 min and responses were monitored for 3 h postinfusion. Results show that at end infusion, mean arterial pressure (RAP), heart rate and plasma volume exhibited peak increases of 146, 23, and 27 percent, respectively. Mean plasma ANP and UV peaked (45 and 390 percent, respectively) at 30 min postinfusion. Most cardiovascular variables had returned toward control levels by 1 h postinfusion, and net reabsorption of extravascular fluid ensued. It is concluded that since ANP was not significantly increased until 30 min postinfusion, factors other than ANP initiate responses to intravascular fluid loading. These factors include increased vascular pressures, baroreceptor-mediated vasolidation, and hemodilution of plasma proteins. ANP is suggested to mediate, in part, the renal response to saline infusion.

  1. Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats

    PubMed Central

    Carillon, Julie; Gauthier, Audrey; Barial, Sandy; Tournier, Michel; Gayrard, Nathalie; Lajoix, Anne-Dominique; Jover, Bernard

    2016-01-01

    Background In spontaneously hypertensive rats (SHR), a model of human essential hypertension, oxidative stress is involved in the development of cardiac hypertrophy and fibrosis associated with hypertension. Dietary supplementation with agents exhibiting antioxidant properties could have a beneficial effect in remodeling of the heart. We previously demonstrated a potent anti-hypertrophic effect of a specific melon (Cucumis melo L.) concentrate with antioxidant properties in spontaneously hypertensive rats. Relaxin and atrial natriuretic peptide (ANP) were reported to reduce collagen deposition and fibrosis progression in various experimental models. Objective The aim of the present investigation was to test the hypothesis that, beside reduction in oxidative stress, the melon concentrate may act through relaxin, its receptor (relaxin/insulin-like family peptide receptor 1, RXFP1), and ANP in SHR. Design and results The melon concentrate, given orally during 4 days, reduced cardiomyocyte size (by 25%) and totally reversed cardiac collagen content (Sirius red staining) in SHR but not in their normotensive controls. Treatment with the melon concentrate lowered cardiac nitrotyrosine-stained area (by 45%) and increased by 17–19% the cardiac expression (Western blot) of superoxide dismutase (SOD) and glutathione peroxidase. In addition, plasma relaxin concentration was normalized while cardiac relaxin (Western blot) was lowered in treated SHR. Cardiac relaxin receptor level determined by immunohistochemical analysis increased only in treated SHR. Similarly, the melon concentrate reversed the reduction of plasma ANP concentration and lowered its cardiac expression. Conclusions The present results demonstrate that reversal of cardiac fibrosis by the melon concentrate involves antioxidant defenses, as well as relaxin and ANP pathways restoration. It is suggested that dietary SOD supplementation could be a useful additional strategy against cardiac hypertrophy and fibrosis

  2. Potentiation of the depressor responses to atrial natriuretic peptides in conscious SHR by an inhibitor of neutral endopeptidase.

    PubMed

    Seymour, A A; Swerdel, J N; Fennell, S A; Druckman, S P; Neubeck, R; Delaney, N G

    1989-08-01

    In previous studies, neutral endopeptidase (NEP) hydrolyzed the Cys105-Phe106 bond of atrial natriuretic peptides (ANP) in vitro. Three such ring-opened peptides derived from ANP 99-126, 103-126, and 103-123 were inactive in conscious rats. In conscious spontaneously hypertensive rats (SHR) in the present study, 100 mumol/kg, intravenously (i.v.) of the NEP inhibitor, SQ 29,072 (7-[[2-(mercaptomethyl)-1-oxo-3-phenyl-propyl]amino]heptanoic acid), significantly increased the area over the curve (AOC) of the depressor response to 3 nmol/kg of ANP 103-126 from 165 +/- 36 to 792 +/- 350, 1,515 +/- 374, and 828 +/- 164 mm Hg.min at 15, 30, and 60 min after inhibitor treatment. Thirty minutes after 3, 10, 30, and 100 mumol/kg of SQ 29,072, the AOC of 3 nmol/kg of ANP 99-126 increased from 175 +/- 59 mm Hg.min in vehicle-treated rats to 296 +/- 100, 318 +/- 34, 632 +/- 194 (p less than 0.05) and 656 +/- 151 (p less than 0.05) mm Hg.min. Furthermore, 100 mumol/kg of SQ 29,072 potentiated the AOC of human ANP 99-126 and 105-126 and rat ANP 99-126, 103-126, and 103-123, suggesting that the exocyclic N-terminal residues and the C-terminal tripeptide did not influence ANP potentiation by SQ 29,072. In contrast, inhibitors of aminopeptidase, angiotensin-converting enzyme (ACE), and serine protease and an arginine vasopressin (AVP) antagonist did not substantially affect the AOC of 3 nmol/kg ANP 99-126. Finally, SQ 29,072 did not alter the activities of bradykinin, AVP, or angiotensin I or II. In conclusion, NEP may inactivate ANP in vivo by cleavage of susceptible bonds within the ANP ring.

  3. The Atrial Natriuretic Peptide Genetic Variant rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population

    PubMed Central

    Cannone, Valentina; Cefalu’, Angelo Baldassare; Noto, Davide; Scott, Christopher G.; Bailey, Kent R.; Cavera, Giovanni; Pagano, Michele; Sapienza, Michelangelo; Averna, Maurizio R.; Burnett, John C.

    2013-01-01

    OBJECTIVE We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels <40 mg/dL are less frequent (P = 0.05) and obesity tends to be less prevalent (P = 0.07). Importantly, the G allele is associated with a lower prevalence of metabolic syndrome (P = 0.02). After adjusting for BMI, the above associations were attenuated. Independently of age, sex, and BMI, the minor allele is also associated with lower systolic blood pressure (−6.0 mmHg [2.5], P = 0.02) and lower prevalence of hypertension (odds ratio 0.41 [95% CI 0.20–0.83], P = 0.01). CONCLUSIONS The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U.S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome. PMID:23637347

  4. Enhanced Hypertrophy In ob/ob Mice Due To An Impairment in Expression Of Atrial Natriuretic Peptide

    PubMed Central

    Mascareno, Eduardo; Beckles, Daniel; Dhar-Mascareno, Manya; Siddiqui, M.A.Q.

    2009-01-01

    Rationale We investigated the molecular mechanism(s) that play a role in leptin signaling during the development of left ventricular hypertrophy (LVH) due to pressure overload. To this end, ob/ob leptin deficient and C57BL/6J control mice were subjected transverse aortic constriction (TAC). Methods Control sham C57BL/6J and ob/ob mice, along with C57BL/6J and ob/ob leptin deficient mice were subjected transverse aortic constriction (TAC) for 15 days and then evaluated for morphological, physiological, and molecular changes associated with pressure overload hypertrophy. Results Evaluation by echocardiography revealed a significant increase in left ventricular mass (LVmass) and wall thickness in ob/ob mice subjected to transverse aortic constriction (TAC) as compared to C57BL/6J. Analysis of the expression of molecular markers of LVH, such as atrial natriuretic peptide (ANP), revealed a blunted increase in the level of ANP in ob/ob mice as compared to C57BL/6J mice. We observed that leptin plays a role in modulating the transcriptional activity of the promoter of the ANP gene. Leptin acts by regulating NFATc4, a member of the nuclear factor activated T cell (NFAT) family of transcription factors in cardiomyocytes. Our in vivo studies revealed that ob/ob mice subjected to TAC failed to activate the NFATc4 in the heart, however, intraperitoneal injection of leptin in ob/ob mice restored the NFATc4 DNA-binding activity and induced expression of the ANP gene. Conclusion This study establishes the role of leptin as an anti-hypertrophic agent during pressure overload hypertrophy, and suggests that a key molecular event is the leptin mediated activation of NFATc4 that regulates the transcriptional activation of the ANP gene promoter. PMID:19560554

  5. Enhanced hypertrophy in ob/ob mice due to an impairment in expression of atrial natriuretic peptide.

    PubMed

    Mascareno, Eduardo; Beckles, Daniel; Dhar-Mascareno, Manya; Siddiqui, M A Q

    2009-01-01

    We investigated the molecular mechanism(s) that play a role in leptin signaling during the development of left ventricular hypertrophy (LVH) due to pressure overload. To this end, ob/ob leptin deficient and C57BL/6J control mice were subjected transverse aortic constriction (TAC). Control sham C57BL/6J and ob/ob mice, along with C57BL/6J and ob/ob leptin deficient mice were subjected transverse aortic constriction (TAC) for 15 days and then evaluated for morphological, physiological, and molecular changes associated with pressure overload hypertrophy. Evaluation by echocardiography revealed a significant increase in left ventricular mass (LVmass) and wall thickness in ob/ob mice subjected to transverse aortic constriction (TAC) as compared to C57BL/6J. Analysis of the expression of molecular markers of LVH, such as atrial natriuretic peptide (ANP), revealed a blunted increase in the level of ANP in ob/ob mice as compared to C57BL/6J mice. We observed that leptin plays a role in modulating the transcriptional activity of the promoter of the ANP gene. Leptin acts by regulating NFATc4, a member of the nuclear factor activated T cell (NFAT) family of transcription factors in cardiomyocytes. Our in vivo studies revealed that ob/ob mice subjected to TAC failed to activate the NFATc4 in the heart, however, intraperitoneal injection of leptin in ob/ob mice restored the NFATc4 DNA-binding activity and induced expression of the ANP gene. This study establishes the role of leptin as an anti-hypertrophic agent during pressure overload hypertrophy, and suggests that a key molecular event is the leptin mediated activation of NFATc4 that regulates the transcriptional activation of the ANP gene promoter.

  6. Procalcitonin and Midregional-proAtrial Natriuretic Peptide as markers of ischemic stroke: the Northern Manhattan Study

    PubMed Central

    Katan, Mira; Moon, Yeseon P.; Paik, Myunghee C.; Mueller, Beat; Huber, Andreas; Sacco, Ralph L.; Elkind, Mitchell S. V.

    2016-01-01

    Background and Purpose Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke. We hypothesized that selected blood biomarkers of infection (procalcitonin, or PCT), hypothalamic-pituitary-axis function (copeptin), and hemodynamic dysfunction (midregional-pro-atrial natriuretic peptide, or MRproANP) are associated with incident ischemic stroke risk in the multiethnic, urban Northern Manhattan Study (NOMAS) cohort. Methods A nested case-control study was performed among initially stroke-free participants. Cases were defined as first ischemic stroke (n=172). We randomly selected controls among those who did not develop an event (n=344). We calculated Cox proportional hazards models with inverse probability weighting to estimate the association of blood biomarkers with risk of stroke after adjusting for demographic, behavioral, and medical risk factors. Results Those with PCT and MRproANP, but not copeptin, in the top quartile, compared to the lowest quartile, were associated with ischemic stroke (for PCT adjusted HR 1.9, 95% CI 1.0–3.8; for MRproANP adjusted HR 3.5, 95% CI 1.6–7.5). The associations of PCT and MRproANP differed by stroke etiology; PCT-levels in the top quartile were particularly associated with small vessel stroke (adjusted HR 5.1, 95% CI 1.4–18.7) and MRproANP-levels with cardioembolic stroke (adjusted HR 16.3, 95% CI 3.7–70.9). Conclusion Higher levels of procalcitonin, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with ischemic stroke risk. PCT was specifically associated with small vessel and MRproANP with cardioembolic stroke risk. Further study is needed to validate these biomarkers and determine their significance in stroke risk prediction and prevention. PMID:27197849

  7. Effectiveness of brain natriuretic peptide in predicting postoperative atrial fibrillation in patients undergoing non-cardiac thoracic surgery.

    PubMed

    Toufektzian, Levon; Zisis, Charalambos; Balaka, Christina; Roussakis, Antonios

    2015-05-01

    A best evidence topic was written according to a structured protocol. The question addressed was whether plasma brain natriuretic peptide (BNP) levels could effectively predict the occurrence of postoperative atrial fibrillation (AF) in patients undergoing non-cardiac thoracic surgery. A total of 14 papers were identified using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. All studies were prospective observational, and all reported a significant association between BNP and N-terminal (NT)-proBNP plasma levels measured in the immediate preoperative period and the incidence of postoperative AF in patients undergoing either anatomical lung resections or oesophagectomy. One study reported a cut-off value of 30 pg/ml above which significantly more patients suffered from postoperative AF (P < 0.0001), while another one reported that this value could predict postoperative AF with a sensitivity of 77% and a specificity of 93%. Another study reported that patients with NT-proBNP levels of 113 pg/ml or above had an 8-fold increased risk of developing postoperative AF. These findings support that BNP or NT-proBNP levels, especially when determined during the preoperative period, if increased, are able to identify patients at risk for the development of postoperative AF after anatomical major lung resection or oesophagectomy. The same does not seem to be true for lesser lung resections. These high-risk patients might have a particular benefit from the administration of prophylactic antiarrhythmic therapy. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  8. Identification of a cis-acting regulatory element conferring inducibility of the atrial natriuretic factor gene in acute pressure overload.

    PubMed Central

    von Harsdorf, R; Edwards, J G; Shen, Y T; Kudej, R K; Dietz, R; Leinwand, L A; Nadal-Ginard, B; Vatner, S F

    1997-01-01

    To identify the cis-acting regulatory element(s) which control the induction of the atrial natriuretic factor (ANF) gene in acute pressure overload, DNA constructs consisting of promoter elements linked to a reporter gene were injected into the myocardium of dogs, which underwent aortic banding or were sham-operated. Expression of a reporter gene construct harboring the ANF promoter (-3400ANF) was induced 6-12-fold after 7 d of pressure overload. An internal deletion of 556 bp (nucleotide sequence -693 to -137) completely abrogated the inducibility of the ANF reporter gene construct. An activator protein-1 (AP1)-like site (-496 to -489) and a cAMP regulatory element (CRE) (-602 to -596) are located within the deleted sequence. Site-directed mutagenesis of the AP1-like site but not the CRE completely prevented the induction of this construct to acute pressure overload. Further, the AP1-like site was able to confer inducibility of a heterologous promoter (beta-myosin heavy chain) to higher values than controls. Gel mobility shift assay (GMSA) supershift analysis was performed using a radiolabeled probe of the ANF promoter (-506/-483) that included the AP1-like site (ATGAATCA) sequence, as well as a probe converted to contain an AP1 consensus sequence (ATGACTCA). GMSA analysis demonstrated that the ANF AP1-like element could bind both a constitutively expressed factor and the AP1 proteins, and conversion to a true AP1 site increased its affinity for AP1. However, 7 d after the onset of pressure overload, the AP1 proteins were present only at low levels, and the major complex formed by the ANF AP1-like probe was not supershifted by a jun antibody. Using a large animal model of pressure overload, we have demonstrated that a unique cis-acting element was primarily responsible for the overload induction of the ANF gene. PMID:9276748

  9. Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Elesgaray, Rosana; Laughlin, Myriam Mac; Tomat, Analía; Arranz, Cristina; Costa, Maria A.

    2013-01-01

    Introduction The aim of this study was to investigate both the effects of chronic treatment with atrial natriuretic peptide (ANP) on systolic blood pressure (SBP), cardiac nitric oxide (NO) system, oxidative stress, hypertrophy, fibrosis and apoptosis in spontaneously hypertensive rats (SHR), and sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/hr/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). SBP was recorded and nitrites and nitrates excretion (NOx) were determined. After treatment, NO synthase (NOS) activity, eNOS expression, thiobarbituric acid-reactive substances (TBARS) and glutathione concentration were determined in left ventricle, as well as the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). Morphological studies in left ventricle were performed in slices stained with hematoxylin-eosin or Sirius red to identify collagen as a fibrosis indicator; immunohistochemistry was employed for identification of transforming growth factor beta; and apoptosis was evaluated by Tunel assay. Results Female SHR showed lower SBP, higher NO-system activity and less oxidative stress, fibrosis and hypertrophy in left ventricle, as well as higher cardiac NOS activity, eNOS protein content and NOx excretion than male SHR. Although ANP treatment lowered blood pressure and increased NOS activity and eNOS expression in both sexes, cardiac NOS response to ANP was more marked in females. In left ventricle, ANP reduced TBARS and increased glutathione concentration and activity of CAT and SOD enzymes in both sexes, as well as GPx activity in males. ANP decreased fibrosis and apoptosis in hearts from male and female SHR but females showed less end-organ damage in heart. Chronic ANP treatment would ameliorate hypertension and end-organ damage in heart by reducing oxidative stress, increasing NO-system activity, and diminishing fibrosis and

  10. Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.

    PubMed Central

    Kovacic-Milivojević, B; Gardner, D G

    1992-01-01

    Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression. Images PMID:1530876

  11. Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes.

    PubMed

    Lovshin, Julie A; Barnie, Annette; DeAlmeida, Ariana; Logan, Alexander; Zinman, Bernard; Drucker, Daniel J

    2015-01-01

    GLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR). Liraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting. End points included within-subject change from baseline in plasma ANP, Nt-proBNP, office BP, and HR at baseline and over 4 h following a single dose of liraglutide (0.6 mg) and after 21 days of liraglutide (titrated to 1.8 mg) versus placebo administration. Simultaneous 24-h ambulatory BP and HR monitoring and 24-h urine collections were measured at baseline and following 21 days of treatment. Plasma ANP levels did not change significantly after acute (+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 h) or chronic (-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 h) liraglutide administration. Liraglutide significantly increased 24-h and nighttime urinary sodium excretion; however, 24-h systolic BP was not significantly different. Small but significant increases in 24-h and nighttime diastolic BP and HR were observed with liraglutide. Body weight, HbA1c, and cholesterol were lower, and office-measured HR was transiently increased (for up to 4 h) with liraglutide administration. Sustained liraglutide administration for 3 weeks increases urinary sodium excretion independent of changes in ANP or BP in overweight and obese hypertensive patients with type 2 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Ability of B-type natriuretic peptide in predicting postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting.

    PubMed

    Ata, Yusuf; Turk, Tamer; Ay, Derih; Eris, Cuneyt; Demir, Mihriban; Ari, Hasan; Ata, Filiz; Yavuz, Senol; Ozyazicioglu, Ahmet

    2009-08-01

    Atrial fibrillation (AF) is still the most frequent rhythm disturbance after coronary artery surgery. Our aim was to evaluate the predictive value of preoperative brain natriuretic peptide (BNP) levels for determining postoperative new-onset AF in patients undergoing isolated first-time coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). We recruited 144 consecutive patients (51 women and 93 men) who underwent isolated CABG. Preoperative and postoperative data were collected. Preoperative BNP levels were measured the day before surgery. The median preoperative BNP level was 68 pg/mL. Postoperative AF occurred in 36 (25%) of the patients. Univariate analyses showed that both advanced age and median preoperative BNP levels were associated with postoperative AF (63.9 +/- 8 years versus 57.3 +/- 9.8 years, P < .001; 226 pg/mL versus 65.2 pg/mL, P <.001). Both variables remained independent predictors of postoperative AF after multivariate logistic regression analyses. For advanced age, the odds ratio was 1.074 (95% confidence interval [CI], 1.019-1.131; P = .008); for preoperative BNP level, the odds ratio was 1.004 (95% CI, 1.001-1.006; P = .002). A receiver operating characteristic (ROC) curve demonstrated that preoperative BNP level was a predictor of postoperative AF, with an area under the ROC curve of 0.750. A cutoff value of 135 pg/mL for AF demonstrated a 72.2% sensitivity, a 71.2% specificity, a 45.6% positive predictive value, a 88.5% negative predictive value, and a 71.5% accuracy for predicting postoperative AF. Elevated preoperative BNP levels and advanced age together are significant predictors for the development of postoperative AF in patients undergoing isolated CABG with CPB.

  13. The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors.

    PubMed

    Springer, Jeremy; Azer, John; Hua, Rui; Robbins, Courtney; Adamczyk, Andrew; McBoyle, Sarah; Bissell, Mary Beth; Rose, Robert A

    2012-05-01

    Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca(2+) current (I(Ca,L)) and the hyperpolarization-activated current (I(f)). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10nM), BNP increased atrial AP duration and I(Ca,L). Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity.

  14. Relative atrial natriuretic peptide deficiency and inadequate renin and angiotensin II suppression in obese hypertensive men.

    PubMed

    Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B; Linneberg, Allan; Møller, Daniel V; Hedley, Paula L; Christiansen, Michael; Goetze, Jens P; Esler, Murray; Jeppesen, Jørgen L

    2013-07-01

    Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg), and in 27 lean normotensive men (leanNT: body mass index, 20.0-24.9 kg/m(2); 24-hour ambulatory blood pressure, <130/80 mm Hg). All study subjects were medication free. As a surrogate estimate for dietary sodium intake, we measured sodium excretion in a 24-hour urine collection and we measured serum levels of midregional proatrial NP and plasma levels of renin and angiotensin II. The obese men had higher mean (±SD) urinary sodium excretion (obeseHT, 213.6±85.2 mmol; obeseNT, 233.0±70.0 mmol) than the lean normotensive men (leanNT, 155.5±51.7 mmol; P=0.003). ObeseHT had lower (median [interquartile range]) serum midregional proatrial NP levels (49.2 [37.3-64.7] pmol/L) than leanNT (69.3 [54.3-82.9] pmol/L; P=0.003), whereas obeseNT had midregional proatrial NP levels in between (54.1 [43.2-64.7] pmol/L); obeseNT had lower (median [interquartile range]) plasma levels of renin (5.0 [3.0-8.0] mIU/L versus 9.0 [4.0-18.0]) and angiotensin II (2.4 [1.5-3.5] pmol/L versus 4.2 [2.2-7.9]) than obeseHT (P≤0.049), whereas obeseHT had similar plasma levels of renin and angiotensin II as leanNT (P≥0.19). Thus, despite a high sodium intake and a high blood pressure, obese hypertensive men have a relative NP deficiency and an inadequate renin-angiotensin system suppression.

  15. Blockade of Multidrug Resistance-Associated Proteins Aggravates Acute Pancreatitis and Blunts Atrial Natriuretic Factor's Beneficial Effect in Rats: Role of MRP4 (ABCC4).

    PubMed

    Ventimiglia, María Silvia; Najenson, Ana Clara; Perazzo, Juan Carlos; Carozzo, Alejandro; Vatta, Marcelo S; Davio, Carlos A; Bianciotti, Liliana G

    2015-01-06

    We previously reported that atrial natriuretic factor (ANF) stimulates secretin-evoked cAMP efflux through multidrug resistance-associated protein 4 (MRP4) in the exocrine pancreas. Here we sought to establish in vivo whether this mechanism was involved in acute pancreatitis onset in the rat. Rats pretreated with or without probenecid (MRPs general inhibitor) were infused with secretin alone or with ANF. A set of these animals were given repetitive cerulein injections to induce acute pancreatitis. Plasma amylase and intrapancreatic trypsin activities were measured and histological examination of the pancreas performed. Secretin alone activated trypsinogen but induced no pancreatic histological changes. Blockade by probenecid in secretin-treated rats increased trypsin and also induced vacuolization, a hallmark of acute pancreatitis. ANF prevented the secretin response but in the absence of probenecid. In rats with acute pancreatitis, pretreatment with secretin aggravated the disease, but ANF prevented secretin-induced changes. Blockade of MRPs in rats with acute pancreatitis induced trypsinogen activation and larger cytoplasmic vacuoles as well as larger areas of necrosis and edema that were aggravated by secretin but not prevented by ANF. The temporal resolution of intracellular cAMP levels seems critical in the onset of acute pancreatitis, since secretin-evoked cAMP in a context of MRP inhibition makes the pancreas prone to injury in normal rats and aggravates the onset of acute pancreatitis. Present findings support a protective role for ANF mediated by cAMP extrusion through MRP4 and further suggest that the regulation of MRP4 by ANF would be relevant to maintain pancreatic acinar cell homeostasis.

  16. [Effects of chronic volume loading on atrial natriuretic peptide release in human].

    PubMed

    Kawabe, J; Ohsaki, Y; Onodera, S; Inoue, H; Hirayama, T; Akiba, Y; Osanai, S; Sakai, H; Ishida, S; Nakano, H

    1990-11-01

    In the present study, we investigated whether release of hANP increases during mild and long-term volume loading. Eight lung cancer patients in good performance state (five men and three women, 35 to 68 years), who needed to have pre-hydration for cancer chemotherapy with cisplatin, were infused with about seven liters of isotonic saline over 48 hours through Swan-Ganz catheter placed in the pulmonary artery. The mean infusion rate was 0.042 ml/min.kg body weight. During the infusion, change in plasma volume (delta PV) increased by 5.8 + 3.3 (mean +/- SE) %. Right atrial pressure (RAP) did not change significantly, and pulmonary artery wedge pressure (PAWP) increased from 4.3 +/- 1.0 to 5.8 +/- 0.7 mmHg. Plasma hANP was significantly elevated from 50.6 +/- 0.7 to 105.1 +/- 19.3 pg/ml by the second day of the infusion with a suppression of plasma renin activity (PRA) and aldosterone, though plasma ADH did not change. The infusion rate at 20:00 on the first day was the same as that on the second day. Further increase in plasma hANP was shown at 20:00 on the second day compared with the level at the same time on the first day, though RAP, PAWP and delta PV did not change. These results indicate that mild and chronic volume loading increases plasma hANP, and suggest that the prolongation of volume expansion plays an important role in the releasing of hANP in humans.

  17. Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure

    PubMed Central

    Wang, Guogan; Wang, Pengbo; Li, Yishi; Liu, Wenxian; Bai, Shugong; Zhen, Yang; Li, Dongye; Yang, Ping; Chen, Yu; Hong, Lang; Sun, Jianhui; Chen, Junzhu; Wang, Xian; Zhu, Jihong; Hu, Dayi; Li, Huimin; Wu, Tongguo; Huang, Jie; Tan, Huiqiong; Zhang, Jian; Liao, Zhongkai; Yu, Litian; Mao, Yi; Ye, Shaodong; Feng, Lei; Hua, Yihong; Ni, Xinhai; Zhang, Yuhui; Wang, Yang; Li, Wei; Luan, Xiaojun; Sun, Xiaolu; Wang, Sijia

    2016-01-01

    Abstract The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863–2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (−7.74 ± 5.95 vs −1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34–4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.) PMID:26945407

  18. Atrial natriuretic peptide-induced microalbuminuria is associated with endothelial dysfunction in noncomplicated type 1 diabetes patients.

    PubMed

    Vervoort, Gerald; Wetzels, Jack F; Lutterman, Jos A; Bravenboer, Bert; Berden, Jo H; Smits, Paul

    2002-07-01

    Microalbuminuria reflects widespread vascular dysfunction in type 1 diabetes mellitus and results from increased glomerular sieving caused by changes in transglomerular pressure and/or permselectivity characteristics of the glomerular basement membrane. Increased tubular reabsorption or degradation of albumin will offset an early increase in albuminuria. We hypothesized that the infusion of atrial natriuretic peptide (ANP) as a tool to increase glomerular permeability might uncover changes in permselectivity in patients with uncomplicated type 1 diabetes. We investigated whether these patients were characterized by endothelial and/or vascular dysfunction. We therefore studied 46 normoalbuminuric patients (urinary albumin excretion [UAE] < 10 microg/min) with type 1 diabetes and 44 healthy controls. Measurements of renal hemodynamics and albuminuria were performed before (baseline) and during the infusion of ANP (0.01 microg/kg/min). On a separate occasion, endothelial function was assessed by the intra-arterial infusion of acetylcholine (ACh), an endothelial-dependent vasodilator. At baseline, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were greater in patients with diabetes (GFR, 121 +/- 3 versus 106 +/- 2 mL/min/1.73 m(2); ERPF, 558 +/- 16 versus 527 +/- 13 mL/min/1.73 m(2); P < 0.001). The infusion of ANP increased filtration fraction. There were no differences in these responses between groups. UAE was significantly greater in patients with diabetes after the ANP infusion (15.8 +/- 1.4 [+183%] versus 9.5 +/- 1.3 microg/min [+96%]; P < 0.01). A subgroup of patients with diabetes with an enhanced albuminuric response (change in UAE > 2 SD of controls) to ANP infusion (mean UAE, 30.3 +/- 1.0 microg/min; 425% +/- 61%) was characterized by a diminished vasodilatory response to ACh (maximal forearm blood flow, 17.2 +/- 2.9 [+563%] versus 26.3 +/- 2.3 mL/min/dL [+800%] in patients with diabetes with a normal albuminuric response; P < 0

  19. Relationship of Left Atrial Global Peak Systolic Strain with Left Ventricular Diastolic Dysfunction and Brain Natriuretic Peptide Level in Patients Presenting with Non-ST Elevation Myocardial Infarction

    PubMed Central

    Değirmenci, Hüsnü; Bakırcı, Eftal Murat; Demirtaş, Levent; Duman, Hakan; Hamur, Hikmet; Ceyhun, Gökhan; Topal, Ergün

    2014-01-01

    Background In patients presenting with non-ST elevation myocardial infarction, we investigated the relationship of left atrial deformational parameters evaluated by 2-dimensional speckle tracking imaging (2D-STI) with conventional echocardiographic diastolic dysfunction parameters and brain natriuretic peptide level. Material/Methods We enrolled 74 non-ST segment elevation myocardial infarction patients who were treated with percutaneous coronary intervention and 58 healthy control subjects. Non-ST segment elevation myocardial infarction patients had echocardiographic examination 48 h after the percutaneous coronary intervention procedure and venous blood samples were drawn simultaneously. In addition to conventional echocardiographic parameters, left atrial strain curves were obtained for each patient. Average peak left atrial strain values during left ventricular systole were measured. Results BNP values were higher in non-ST segment elevation myocardial infarction patients compared to controls. Mean left atrium peak systolic global longitudinal strain in Group 2 (the control group) was higher than in the non-ST segment elevation myocardial infarction group. Left atrium peak systolic global longitudinal strain was significantly correlated with left ventricular ejection fraction. There was a significant inverse correlation between left atrium peak systolic global longitudinal strain and brain natriuretic peptide level, left atrium volume maximum, and left atrium volume minimum. Conclusions Our study shows that Left atrium peak systolic global longitudinal strain values decreased consistently with deteriorating systolic and diastolic function in non-ST segment elevation myocardial infarction patients treated with percutaneous coronary intervention. Left atrium peak systolic global longitudinal strain measurements may be helpful as a complimentary method to evaluate diastolic function in this patient population. PMID:25338184

  20. Relationship of left atrial global peak systolic strain with left ventricular diastolic dysfunction and brain natriuretic peptide level in patients presenting with non-ST elevation myocardial infarction.

    PubMed

    Değirmenci, Hüsnü; Bakırcı, Eftal Murat; Demirtaş, Levent; Duman, Hakan; Hamur, Hikmet; Ceyhun, Gökhan; Topal, Ergün

    2014-10-22

    In patients presenting with non-ST elevation myocardial infarction, we investigated the relationship of left atrial deformational parameters evaluated by 2-dimensional speckle tracking imaging (2D-STI) with conventional echocardiographic diastolic dysfunction parameters and brain natriuretic peptide level. We enrolled 74 non-ST segment elevation myocardial infarction patients who were treated with percutaneous coronary intervention and 58 healthy control subjects. Non-ST segment elevation myocardial infarction patients had echocardiographic examination 48 h after the percutaneous coronary intervention procedure and venous blood samples were drawn simultaneously. In addition to conventional echocardiographic parameters, left atrial strain curves were obtained for each patient. Average peak left atrial strain values during left ventricular systole were measured. BNP values were higher in non-ST segment elevation myocardial infarction patients compared to controls. Mean left atrium peak systolic global longitudinal strain in Group 2 (the control group) was higher than in the non-ST segment elevation myocardial infarction group. Left atrium peak systolic global longitudinal strain was significantly correlated with left ventricular ejection fraction. There was a significant inverse correlation between left atrium peak systolic global longitudinal strain and brain natriuretic peptide level, left atrium volume maximum, and left atrium volume minimum. Our study shows that Left atrium peak systolic global longitudinal strain values decreased consistently with deteriorating systolic and diastolic function in non-ST segment elevation myocardial infarction patients treated with percutaneous coronary intervention. Left atrium peak systolic global longitudinal strain measurements may be helpful as a complimentary method to evaluate diastolic function in this patient population.

  1. The natriuretic peptides.

    PubMed

    Baxter, Gary F

    2004-03-01

    The natriuretic peptides are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of actions throughout the body. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their volume regulating effects. These pleiotropic actions include local (autocrine/paracrine) regulatory actions of ANP and BNP within the heart, and of another natriuretic peptide, CNP, within the vessel wall. Effects on function and growth of the local tissue environment are likely to be of great importance, especially in disease states where tissue and circulating levels of ANP and BNP rise markedly. At present, the relevance of other natriuretic peptides (notably uroguanylin and DNP) to human physiology and pathology remain uncertain. Other articles in this issue of Basic Research in Cardiology review the molecular physiology of natriuretic peptide signalling, with a particular emphasis on the lessons from genetically targetted mice; the vascular activity of natriuretic peptides; the regulation and roles of natriuretic peptides in ischaemic myocardium; and the diagnostic, prognostic and therapeutic roles of natriuretic peptides in heart failure.

  2. Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function

    NASA Technical Reports Server (NTRS)

    Yalcin, F.; Aksoy, F. G.; Muderrisoglu, H.; Sabah, I.; Garcia, M. J.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

  3. Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function

    NASA Technical Reports Server (NTRS)

    Yalcin, F.; Aksoy, F. G.; Muderrisoglu, H.; Sabah, I.; Garcia, M. J.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

  4. Pseudomonas aeruginosa Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation.

    PubMed

    Rosay, Thibaut; Bazire, Alexis; Diaz, Suraya; Clamens, Thomas; Blier, Anne-Sophie; Mijouin, Lily; Hoffmann, Brice; Sergent, Jacques-Aurélien; Bouffartigues, Emeline; Boireau, Wilfrid; Vieillard, Julien; Hulen, Christian; Dufour, Alain; Harmer, Nicholas J; Feuilloley, Marc G J; Lesouhaitier, Olivier

    2015-08-25

    in the human lung, in which bacteria are in contact with host molecular messengers such as hormones. The C-type natriuretic peptide (CNP), a hormone produced by lung cells, has been described as a bacterial virulence enhancer. In this study, we showed that the CNP hormone counteracts P. aeruginosa biofilm formation and we identified the bacterial protein AmiC as the sensor involved in the CNP effects. We showed that AmiC could bind specifically CNP. These results show for the first time that a human hormone could be sensed by bacteria through a specific protein, which is an ortholog of the human receptor NPR-C. The bacterium would be able to modify its lifestyle by favoring virulence factor production while reducing biofilm formation. Copyright © 2015 Rosay et al.

  5. Immunoreactive prohormone atrial natriuretic peptides 1-30 and 31-67 - Existence of a single circulating amino-terminal peptide

    NASA Technical Reports Server (NTRS)

    Chen, Yu-Ming; Whitson, Peggy A.; Cintron, Nitza M.

    1990-01-01

    Sep-Pak C18 extraction of human plasma and radioimmunoassay using antibodies which recognize atrial natriuretic peptide (99-128) and the prohormone sequences 1-30 and 31-67 resulted in mean values from 20 normal subjects of 26.2 (+/- 9.2), 362 (+/- 173) and 368 (+/- 160) pg/ml, respectively. A high correlation coefficient between values obtained using antibodies recognizing prohormone sequences 1-30 and 31-67 was observed (R = 0.84). Extracted plasma immunoreactivity of 1-30 and 31-67 both eluted at 46 percent acetonitrile. In contrast, chromatographic elution of synthetic peptides 1-30 and 31-67 was observed at 48 and 39 percent acetonitrile, respectively. Data suggest that the radioimmunoassay of plasma using antibodies recognizing prohormone sequences 1-30 and 31-67 may represent the measurement of a unique larger amino-terminal peptide fragment containing antigenic sites recognized by both antisera.

  6. Role of atrial natriuretic factor, hemodynamic changes and renal nerves in the renal effects of intraperitoneal morphine in conscious rats.

    PubMed

    Flores, O; Camera, L A; Hergueta, A; Gallego, B; Pérez Barriocanal, F; Gutkowska, J; López Novoa, J M

    1997-01-01

    The aim of the present study was to investigate the role of renal nerves and atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis and antinatriuresis induced by morphine in rats in a normal state of hydration. Male Wistar rats weighing 350-400 g were divided into two groups: one group was subjected to bilateral renal denervation, whereas the other consisted of sham-operated controls. The animals were placed in individual metabolic cages, and morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic saline) was injected intraperitoneally. Urine was collected hourly for 1 h before and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg body weight) induced a transient increase in urine output (from 1.17+/-0.12 to 2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.18 microl/min, respectively). The diuretic response to these doses was similar in bilaterally denervated rats. Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to 0.48+/-0.05 and from 1.37+/-0.17 to 0.45+/-0.08 microl/min, respectively), followed by a delayed diuretic effect. The antidiuretic action of morphine was not observed in bilaterally denervated rats. In control rats, morphine induced a dose-dependent decrease in sodium excretion 1 h after administration, an effect that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5 mg/kg body weight) elicited a transient increase in the glomerular filtration rate (GFR) in both control (from 1.23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14 to 2.41+/-0.18 ml/min) and bilaterally denervated rats (from 1.29+/-0.14 to 1.66+/-0.17 and from 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 to 0.47+/-0.08 ml/min) and

  7. Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries.

    PubMed Central

    Fujii, K; Ishimatsu, T; Kuriyama, H

    1986-01-01

    Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a

  8. Effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide in rat atria: an in vitro study.

    PubMed

    Soualmia, Hayet; Abroug, Fekri; Djeridane, Yasmina

    2008-03-01

    Scorpion envenomation is considered public health problem in Northern African countries. The mechanisms of cardiac dysfunction following scorpion envenomation are not fully understood. This study examined the effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide (ANP) release from rat atrium using in vitro organ perifusion. Male Sprague Dawley rats were used in this study. Three experiments were conducted. In experiment 1, atrial tissues were exposed either to Krebs-bicarbonate buffer medium (control) or to scorpion toxin (10(-8) M to 10(-6) M). In experiment 2, animals were chemically sympathectomized with a single intraperitoneal injection of 6-hydroxydopamine (6-OHDOPA) at a dose of 40 microg/g 24 h before sacrifice. Vehicle-treated rats served as control. Atrial tissues were collected and perifused in the presence of 10(-6) M scorpion toxin. In experiment 3, atrial tissues were exposed to 10(-6) M scorpion toxin either in the absence or presence of 10(-6) M propranolol (a beta-adrenoceptor blocker), or 10(-6) M tetrodotoxin (a sodium channel blocker). ANP levels released in the perifusion medium were determined by radioimmunoassay. The scorpion toxin at 10(-6) M induced a significant (p<0.01) increase (106%) in ANP levels. This effect was decreased (20%) by 6-OHDOPA. Propranolol and tetrodotoxin significantly (p<0.01) inhibited 55% and 60%, respectively, the toxin-induced ANP release. The data show that the North African scorpion toxin from Androctonus australis garzonii increases the ANP release in rat atrium through stimulation of sympathetic cardiac nerves and sodium channels activation.

  9. Inhibition by atrial and brain natriuretic peptides of endothelin-1 secretion after stimulation with angiotensin II and thrombin of cultured human endothelial cells.

    PubMed Central

    Kohno, M; Yasunari, K; Yokokawa, K; Murakawa, K; Horio, T; Takeda, T

    1991-01-01

    We examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion stimulated by angiotensin II (ANGII) and thrombin using cultured human umbilical-vein endothelial cells. ANGII and thrombin dose-dependently stimulated immunoreactive (ir) endothelin-1 secretion. Human ANP(1-28) and human BNP-32 both inhibited such secretion in a dose-dependent way. Inhibition of this secretion by ANP and BNP was paralleled by an increase in the level of cyclic guanosine 5'-monophosphate (GMP). The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, reduced this stimulated secretion. Rat ANP(5-25) was weaker than human ANP(1-28) at inhibiting ir-endothelin-1 secretion and increasing cyclic GMP in the cells. ir-Endothelin-1 in the medium consisted of two components separated by high pressure liquid chromatography; the major one corresponded to endothelin-1(1-21) and the minor one corresponded to big endothelin-1(1-38). Treatment with ANP and BNP did not affect this profile. These findings suggest that human ANP and BNP inhibit endothelin-1 secretion stimulated by ANGII and thrombin in these cells through a cyclic GMP-dependent process. Taken together with endothelin stimulation of ANP and BNP secretion from the heart, our results suggest the existence of a cardiac-endothelium feedback. PMID:1645748

  10. A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

    PubMed

    Kamiya, Masataka; Sato, Naoki; Akiya, Mai; Okazaki, Hirotake; Takahashi, Yasuhiro; Mizuno, Kyoichi

    2013-01-01

    Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

  11. N-terminal pro-B-type Natriuretic Peptide is a Major Predictor of the Development of Atrial Fibrillation: The Cardiovascular Health Study

    PubMed Central

    Patton, Kristen K.; Ellinor, Patrick T.; Heckbert, Susan R.; Christenson, Robert H.; DeFilippi, Christopher; Gottdiener, John S.; Kronmal, Richard A.

    2014-01-01

    Background Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and health care expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, atrial fibrillation, and mortality. Methods and Results The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5,445 Cardiovascular Health Study participants, using relative risk regression for predicting prevalent AF, and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95%CI 17.9, 913.3, p< 0.001); and adjusted prevalence ratio of 147 for the highest quintile (95% CI 20.4, 1064.3, p<0.001) compared to the lowest. After a median follow up of 10 years (maximum of 16 years), there were 1,126 cases of incident AF (a rate of 2.2 per 100 person years). NT-proBNP was highly predictive of incident AF with an unadjusted hazard ratio of 5.2 (95% CI 4.3, 6.4, p < 0.001) for the development of AF for the highest quintile compared to the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes, and heart failure; with an adjusted hazard ratio of 4.0 (CI 3.2, 5.0, p< 0.001). Conclusions In a community based population of older adults, NT-pro BNP was a remarkable predictor of incident AF, independent of any other previously described risk factor. PMID:19841297

  12. Doppler index and plasma level of atrial natriuretic hormone are improved by optimizing atrioventricular delay in atrioventricular block patients with implanted DDD pacemakers.

    PubMed

    Toda, N; Ishikawa, T; Nozawa, N; Kobayashi, I; Ochiai, H; Miyamoto, K; Sumita, S; Kimura, K; Umemura, S

    2001-11-01

    Doppler index is the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and has clinical value as an index of combined systolic and diastolic myocardial performance. This crossover study compared the Doppler index and atrial natriuretic hormone (atrial natriuretic peptide) [ANP] between optimal (AV) delay and prolonged AV delay in patients with DDD pacemakers. The study included 14 patients (6 men, 8 women, age 78.4+/-9.3 [SD] years) with AV block with an implanted DDD pacemaker. AV delay was prolonged in a 25-ms, stepwise fashion starting from 125 ms to 250 ms. Pacing rate was set at 70 beats/min. Cardiac output (CO) was assessed by pulsed Doppler echocardiography, and optimal AV delay was defined as the AV delay at which CO was maximum, and an AV delay setting of 250 ms as prolonged AV delay. Plasma level of ANP and Doppler index determined by echocardiography were measured 1 week after programming. AV delay was switched to another AV delay and measurements were repeated after 1 week. Optimal AV delay was 159+/-19 ms. Doppler index was significantly lower at optimal AV delay than at prolonged AV delay (0.68+/-0.26 vs 0.92+/-0.30, P < 0.05). The plasma ANP level was significantly lower at optimal AV delay than at prolonged AV delay (29.0+/-30.7 vs 52.6+/-44.9 pg/mL, P < 0.05). In conclusion, the Doppler index and the plasma ANP level were significantly lower at optimal AV delay than at prolonged AV delay. This study shows the importance of the optimal AV delay setting in patients with an implanted DDD pacemaker, the Doppler index and plasma ANP levels are good indicators for optimizing AV delay.

  13. Increased extracellular water measured by bioimpedance and by increased serum levels of atrial natriuretic peptide in RA patients-signs of volume overload.

    PubMed

    Straub, Rainer H; Ehrenstein, Boris; Günther, Florian; Rauch, Luise; Trendafilova, Nadezhda; Boschiero, Dario; Grifka, Joachim; Fleck, Martin

    2017-05-01

    The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.

  14. N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

    PubMed

    Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

    2015-10-01

    We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

  15. Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure.

    PubMed

    Liu, Chao; Chen, Ying; Kang, Yunxiao; Ni, Zhihua; Xiu, Heming; Guan, Jing; Liu, Kunshen

    2011-10-01

    In heart failure, the renal responsiveness to exogenous and endogenous atrial natriuretic peptide (ANP) is blunted. The mechanisms of renal hyporesponsiveness to ANP are complex, but one potential mechanism is decreased expression of natriuretic peptide receptor-A (NPR-A) in inner medullary collecting duct (IMCD) cells. Newly emerging evidence shows that glucocorticoids could produce potent diuresis and natriuresis in patients with heart failure, but the precise mechanism is unclear. In the present study, we found dexamethasone (Dex) dramatically increased the expression of NPR-A in IMCD cells in vitro. The NPR-A overexpression induced by Dex presented in a time- and dose-dependent manner, which emerged after 12 h and peaked after 48 h. The cultured IMCD cells were then stimulated with exogenous rat ANP. Consistent with the findings with NPR-A expression, Dex greatly increased cGMP (the second messenger for the ANP) generation in IMCD cells, which presented in a time- and dose-dependent manner as well. In rats with decompensated heart failure, Dex dramatically increased NPR-A expression in inner renal medulla, which was accompanied by a remarkable increase in renal cGMP generation, urine flow rate, and renal sodium excretion. It is noteworthy that Dex dramatically lowered plasma ANP, cGMP levels, and left ventricular end diastolic pressure. These favorable effects induced by Dex were glucocorticoid receptor (GR)-mediated and abolished by the GR antagonist 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one (RU486). Collectively, glucocorticoids could improve renal responsiveness to ANP by up-regulating NPR-A expression in the IMCD and induce a potent diuretic action in rats with decompensated heart failure.

  16. Natriuretic peptide metabolism, clearance and degradation.

    PubMed

    Potter, Lincoln R

    2011-06-01

    Atrial natriuretic peptide, B-type natriuretic peptide and C-type natriuretic peptide constitute a family of three structurally related, but genetically distinct, signaling molecules that regulate the cardiovascular, skeletal, nervous, reproductive and other systems by activating transmembrane guanylyl cyclases and elevating intracellular cGMP concentrations. This review broadly discusses the general characteristics of natriuretic peptides and their cognate signaling receptors, and then specifically discusses the tissue-specific metabolism of natriuretic peptides and their degradation by neprilysin, insulin-degrading enzyme, and natriuretic peptide receptor-C.

  17. Natriuretic Peptide Metabolism, Clearance and Degradation

    PubMed Central

    Potter, Lincoln R.

    2015-01-01

    Atrial natriuretic peptide, B-type natriuretic peptide and C-type natriuretic peptide compose a family of three structurally related, but genetically distinct, signaling molecules that regulate the cardiovascular, skeletal, nervous, reproductive and other systems by activating transmembrane guanylyl cyclases and elevating intracellular cGMP concentrations. This review broadly discusses the general characteristics of natriuretic peptides and their cognate signaling receptors, then specifically discusses the tissue specific metabolism of natriuretic peptides and their degradation by neprilysin, insulin-degrading enzyme and natriuretic peptide receptor-C. PMID:21375692

  18. Differential Role of Nkx2-5 in Activation of the Atrial Natriuretic Factor Gene in the Developing versus Failing Heart ▿ †

    PubMed Central

    Warren, Sonisha A.; Terada, Ryota; Briggs, Laura E.; Cole-Jeffrey, Colleen T.; Chien, Wei-Ming; Seki, Tsugio; Weinberg, Ellen O.; Yang, Thomas P.; Chin, Michael T.; Bungert, Jörg; Kasahara, Hideko

    2011-01-01

    Atrial natriuretic factor (ANF) is abundantly expressed in atrial cardiomyocytes throughout ontogeny and in ventricular cardiomyocytes in the developing heart. However, during cardiac failure and hypertrophy, ANF expression can reappear in adult ventricular cardiomyocytes. The transcription factor Nkx2-5 is one of the major transactivators of the ANF gene in the developing heart. We identified Nkx2-5 binding at three 5′ regulatory elements (kb −34, −31, and −21) and at the proximal ANF promoter by ChIP assay using neonatal mouse cardiomyocytes. 3C analysis revealed close proximity between the distal elements and the promoter region. A 5.8-kb fragment consisting of these elements transactivated a reporter gene in vivo recapitulating endogenous ANF expression, which was markedly reduced in tamoxifen-inducible Nkx2-5 gene knockout mice. However, expression of a reporter gene was increased and expanded toward the outer compact layer in the absence of the transcription repressor Hey2, similar to endogenous ANF expression. Functional Nkx2-5 and Hey2 binding sites separated by 59 bp were identified in the −34 kb element in neonatal cardiomyocytes. In adult hearts, this fragment did not respond to pressure overload, and ANF was induced in the absence of Nkx2-5. These results demonstrate that Nkx2-5 and its responsive cis-regulatory DNA elements are essential for ANF expression selectively in the developing heart. PMID:21930795

  19. Influence of training habits on exercise-induced changes in plasma atrial and brain natriuretic peptide and urinary excretion of aquaporin-2 in healthy man.

    PubMed

    Bentzen, H; Pedersen, R S; Nyvad, O; Pedersen, E B

    2002-01-01

    The purpose of this study was to quantify the influence of training habits on the changes in plasma atrial natriuretic peptide (ANP), plasma brain natriuretic peptide (BNP) and urine aquaporin-2 (u-AQP2) during exercise by studying trained and untrained healthy subjects. Eleven trained subjects (7 males, 4 females) and 10 untrained subjects (8 males, 2 females) performed a maximal aerobic exercise test. ANP and BNP were determined every 3 min and at maximum exercise by radioimmunoassay (RIA), and u-AQP2 was determined before and after the exercise test by RIA. The absolute increase in ANP during exercise was higher in the trained subjects (trained subjects: 5.6 pmol/L; untrained subjects: 2.4 pmol/L, p < 0.05) and was positively correlated to ANP at rest (p < 0.03). The maximum absolute increase in BNP during exercise was the same in the two groups (trained subjects: 0.5 pmol/L; untrained subjects: 0.6 pmol/L, NS) and tended to correlate positively with resting BNP in the trained subjects (p = 0.07). Exercise did not change u-AQP2 excretion in either trained subjects (rest: 372 ng/mmol creatinine; exercise: 314 ng/mmol creatinine, NS) or untrained subjects (rest: 263 ng/mmol creatinine; exercise: 338 ng/mmol creatinine, NS). The absolute increase in ANP during exercise was higher in trained subjects than in untrained subjects and was positively correlated to ANP at rest. This might reflect the normal cardiovascular adaptation to exercise. The increase in BNP during exercise was unrelated to training habits. Training habits did not affect the u-AQP2 excretion during exercise.

  20. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

    PubMed

    Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

    2013-06-04

    This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). Copyright

  1. Brain natriuretic peptide as a biomarker of systemic right ventricular function in patients with transposition of great arteries after atrial switch operation.

    PubMed

    Chow, Pak-Cheong; Cheung, Eddie Wai-Yin; Chong, Chun-Yin; Lun, Kin-Shing; Yung, Tak-Cheung; Wong, Kin-Tak; Chau, Adolphus Kai-Tung; Cheung, Yiu-Fai

    2008-07-04

    Assessment of systemic right ventricular (RV) function is inherently difficult. In adults, plasma brain natriuretic peptide (BNP) level has been shown to reflect systemic ventricular dysfunction. We sought to test the hypothesis that plasma BNP is a biomarker of systemic RV function in patients after atrial switch operation. We determined the RV function in 44 patients, 35 after Senning and 9 after Mustard operation, aged 19.7+/-4.0 years, by tissue Doppler echocardiography and determination of myocardial performance index (MPI). The results were compared to the left ventricular function of 14 age-matched controls. Their plasma BNP levels were correlated with indices of systemic ventricular function. Compared with controls, the patients had greater MPI (p<0.001), lower systemic ventricular free wall-annular early diastolic (p<0.001), late diastolic (p<0.001), and systolic velocities (p=0.001), lower septal-annular early diastolic (p<0.001), late diastolic (p<0.001), and systolic velocities (p<0.001), and higher BNP levels (p=0.03). Plasma BNP levels correlated positively with MPI (r=0.43, p=0.001) and negatively with the free wall- and septal-annular myocardial velocities (r=-0.32 to -0.47, p<0.05). The area under the receiver operating characteristic curve for BNP to detect ventricular dysfunction (MPI >0.45) in patients was 0.67 (p=0.04). A BNP level of 36 pg/ml had a sensitivity of 55%, specificity of 86%, positive predictive value 80%, negative predictive value of 64%, and an accuracy of 70% for detecting systemic ventricular dysfunction. Plasma BNP has modest accuracy in the detection of systemic RV dysfunction in patients after atrial switch operation.

  2. Carotid-femoral pulse wave velocity is associated with N-terminal pro-B-type natriuretic peptide level in patients with atrial fibrillation.

    PubMed

    Chen, Lin Y; Tai, Bee C; Foo, David C; Wong, Raymond C; Adabag, A Selcuk; Benditt, David G; Ling, Lieng H

    2011-01-01

    To determine the extent to which conduit artery stiffness is associated with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF). Cross-sectional study. National University Hospital, Singapore. Cases (n=117) were patients with AF onset <65 years of age without heart failure or structural heart disease. Controls (n=274) were patients without AF who were seen at the general cardiology clinic. Transthoracic echocardiography, carotid-femoral pulse wave velocity (CFPWV) measured using applanation tonometry and blood draw for plasma NT-proBNP at enrolment for all patients. Plasma NT-proBNP. In patients with AF, CFPWV was associated with NT-proBNP after adjusting for hypertension and factors that were univariately associated with NT-proBNP: age at enrolment, type of AF, body mass index, left ventricular mass index, left atrial volume index, mitral E/E', mitral deceleration time and use of β-blockers (β=0.234; 95% CI 0.100 to 0.367; p=0.001). In contrast, CFPWV was not associated with NT-proBNP in controls. In patients with AF, the adjusted mean NT-proBNP level in the highest quartile of CFPWV (350 pg/ml; 95% CI 237 to 517 pg/ml) was fivefold higher than the lowest quartile (69 pg/ml; 95% CI 47 to 103 pg/ml) (p=0.001). CFPWV is associated with NT-proBNP level in AF. Since elevated NT-proBNP is a marker of adverse cardiovascular outcomes, arterial stiffness may be associated with worse prognosis in patients with AF.

  3. The guanylyl cyclase-A receptor transduces an atrial natriuretic peptide/ATP activation signal in the absence of other proteins.

    PubMed

    Wong, S K; Ma, C P; Foster, D C; Chen, A Y; Garbers, D L

    1995-12-22

    Attempts to activate partially purified preparations of the guanylyl cyclase-A (GC-A) receptor with atrial natriuretic peptide (ANP) have previously failed, leading to speculation that essential cofactors are lost during purification procedures. The receptor was modified to contain the FLAG epitope (DYKDDDDK), expressed in Sf9 cells, and purified to apparent homogeneity (4.3 mumol cyclic GMP formed/min/mg protein; 5.8 mmol 125I-ANP binding site/mg protein) by a combination of immunoaffinity, Q-Sepharose FF, and wheat germ agglutinin batch chromatography. High initial protein/detergent ratios, the presence of glycerol (40%), and the inclusion of protein phosphatase inhibitors in all buffers resulted in the purification of a receptor that continued to transduce the ANP/ATP activation signal. Both native and purified GC-A contained a single class of high affinity ANP binding sites (Kd = 60 pM) and an equivalent EC50 for ATP (0.3 mM). Positive cooperativity as a function of MnGTP was retained during purification. Thus, GC-A is capable of transducing a ligand binding signal in the absence of other proteins.

  4. Alpha(1)- and beta-adrenoceptor stimulation differentially activate p38-MAPK and atrial natriuretic peptide production in the perfused amphibian heart.

    PubMed

    Aggeli, Ioanna-Katerina S; Gaitanaki, Catherine; Lazou, Antigone; Beis, Isidoros

    2002-08-01

    We investigated the activation of p38-MAPK by various adrenergic agents in the perfused Rana ridibunda heart. Phenylephrine (50 micromol l(-1)) rapidly induced the differential activation of all three mitogen-activated protein kinase (MAPK) subfamilies (ERK, JNKs and p38-MAPK) in this experimental system. Focusing on p38-MAPK response to phenylephrine, we found that the kinase phosphorylation reached maximal values at 30 s, declining thereafter to basal values at 15 min. p38-MAPK activation by phenylephrine was verified as exclusively alpha(1)-AR-mediated. Furthermore, SB203580 (1 micromol l(-1)) abolished the kinase phosphorylation by phenylephrine. Isoproterenol (50 micromol l(-1)) was also shown to activate p38-MAPK in a time- and temperature-dependent manner. A marked, sustained p38-MAPK activation profile was observed at 25 degrees C, while at 18 degrees C the kinase response to isoproterenol was modest. Isoproterenol effect on p38-MAPK stimulation was beta-AR-mediated. Immunohistochemical studies revealed the enhanced presence of phosphorylated p38-MAPK and atrial natriuretic peptide (ANP) in both phenylephrine- and isoproterenol-stimulated hearts, a reaction completely blocked by the respective specific antagonists, or the specific p38-MAPK inhibitor SB203580. These findings indicate a functional correlation between p38-MAPK activation and ANP accumulation in the perfused amphibian heart.

  5. Human atrial natriuretic peptide infusion for a neonate with congestive heart failure after total correction of total anomalous pulmonary venous connection.

    PubMed

    Hamawaki, M; Tomino, T; Sato, H; Imura, M; Suzuki, T; Hibino, N

    2000-09-01

    A successful case of human atrial natriuretic peptide (HANP) infusion therapy for a neonate who developed congestive heart failure (CHF) after total repair of total anomalous pulmonary venous connection was performed on the first day of life. Following 14h of HANP infusion at incremental doses of 0.125-0.25 microg x kg(-1) x min(-1) urine output and hemodynamics dramatically improved. Urine output increased from 1.1 to 10.6 ml/h (p<0.0001) and good urinary output (13.0 ml/h) was maintained even after discontinuation of the infusion. During the infusion, the heart rate decreased from 166 to 152 beats/min (p<0.0001), and the systemic systolic blood pressure increased from 82 to 103 mmHg (p<0.0001). Central venous pressure was not significantly affected by HANP infusion. This is the first successful case of HANP infusion therapy as the first treatment of post-operative pulmonary hypertension in this age group. This therapy can be used safely and may be useful in neonates with CHF resulting from other causes, but more investigation is needed.

  6. Atrial natriuretic peptide-conjugated chitosan-hydrazone-mPEG copolymer nanoparticles as pH-responsive carriers for intracellular delivery of prednisone.

    PubMed

    M, Gover Antoniraj; C, Senthil Kumar; Henry, Linda Jeeva Kumari; Natesan, Subramanian; Kandasamy, Ruckmani

    2017-02-10

    A chitosan-hydrazone-mPEG (CH-Hz-mPEG) copolymer which is stable at extracellular pH and cleaves at slightly acidic intracellular pH was synthesized and characterized. Blank polymeric nanoparticles (B-PNPs) and prednisone-loaded polymeric nanoparticles (P-PNPs) were then formulated by dialysis/precipitation method. The cell-specific ligand, atrial natriuretic peptide (ANP) was then conjugated to P-PNPs (ANP-P-PNPs) by a coupling reaction. Particle size and morphological analyses revealed uniform spherical shape of PNPs. In vitro pH dependent degradation of PNPs was investigated. Drug release profile of ANP-P-PNPs indicated a slow release of prednisone at pH 7.4, but a rapid release at pH 5.0 due to the cleavage of hydrazone linkage. Cytotoxicity studies demonstrated greater compatibility of B-PNPs compared to ANP-P-PNPs. Cellular internalization of ANP-P-PNPs was higher than P-PNPs owing to receptor-mediated endocytosis. The results from this investigation support the hypothesis that chitosan based ANP-P-PNPs could act as an intracellular pH-responsive and targeted drug delivery system.

  7. Change in plasma immunoreactive N-terminus, C-terminus, and 4,000-dalton midportion of atrial natriuretic factor prohormone with hemodialysis.

    PubMed

    Winters, C J; Vesely, D L

    1991-01-01

    Plasma concentrations of the immunoreactive N-terminus, C-terminus and 4,000-dalton midportion of the N-terminus of the atrial natriuretic factor (ANF) prohormone were measured before and after hemodialysis in 13 patients with end-stage renal disease. There was a significant (p less than 0.001) fall in the mean plasma concentration of the C-terminus (i.e. ANF, amino acids 99-126 of the prohormone) from 123 +/- 25 to 80 +/- 22 fmol/ml (mean +/- SEM) with dialysis. The whole N-terminus, on the other hand, increased from 9,336 +/- 2,011 to 11,021 +/- 2,134 fmol/ml after dialysis (p less than 0.002). Pro ANF 31-67 (i.e. amino acids 31-67 of the prohormone) increased postdialysis from 27,775 +/- 4,300 to 31,040 +/- 4,840 fmol/ml (p less than 0.003). Only 1.5% of pro ANF 1-98 and pro ANF 31-67 were cleared by the dialyzer membrane while 15% of ANF crossed the membrane. Thus, with hemodialysis the C-terminus decreases while the N-terminus and pro ANF 31-67 from the midportion of the N-terminus of the ANF prohormone increase in plasma which is partially explained by their respective abilities to cross the dialyzer membrane.

  8. Measurement of cytoplasmic free Ca2+ concentration in rabbit aorta using the photoprotein, aequorin. Effect of atrial natriuretic peptide on agonist-induced Ca2+ signal generation.

    PubMed Central

    Takuwa, Y; Rasmussen, H

    1987-01-01

    Addition of norepinephrine, angiotensin II, or histamine leads to a transient rise in the cytoplasmic Ca2+ concentration ([Ca2+]i), as measured with aequorin, in rabbit aortic strips. Each induces a [Ca2+]i transient which peaks in 2 min and then falls either back to baseline (angiotensin II) or to a plateau (norepinephrine and histamine). The [Ca2+]i transient is due to the mobilization of Ca2+ from a caffeine-sensitive, intracellular pool. An elevation of [K+] to 35 mM leads to a monotonic sustained rise in [Ca2+]i which depends entirely on extracellular Ca2+, but an increase to 100 mM leads to a [Ca2+]i transient from the mobilization of intracellular Ca2+. Atrial natriuretic peptide does not alter basal [Ca2+]i nor inhibit the [Ca2+]i transient induced by either histamine or angiotensin II, but blocks that induced by norepinephrine, and blocks the plateau phase induced by either histamine or norepinephrine. The peptide inhibits the contractile response to all three agonists and to K+. PMID:2439545

  9. Partial characterization of a metalloendopeptidase activity produced by cultured endothelial cells that removes the COOH-terminal tripeptide from sup 125 I-atrial natriuretic factor

    SciTech Connect

    Johnson, G.R.; Foster, C.J. )

    1990-02-28

    The presence of the COOH-terminal region of human atrial natriuretic factor-(99-126) (hANF) is necessary for the full expression of its biological activity. Here, we report on the partial characterization of a proteolytic activity in the conditioned medium from cultured bovine aortic endothelial cells that cleaves the Ser123-Phe124 bond of {sup 125}I-hANF generating the COOH-terminal tripeptide. The concentrated conditioned medium was fractionated by gel filtration high performance liquid chromatography and fractions were assayed for the ability to generate the COOH-terminal tripeptide from {sup 125}I-hANF. This analysis indicated that the protein responsible for this activity had an approximate molecular weight of 200,000 daltons. Of 16 protease inhibitors tested, only 1,10 phenanthroline, EDTA, EGTA and N-ethylmaleimide significantly inhibited the endopeptidase activity. Thus, we conclude that cultured bovine aortic endothelial cells produce a potentially novel phosphoramidon-insensitive metalloendopeptidase that removes the COOH-terminal tripeptide from {sup 125}I-hANF.

  10. Association between the N-terminal plasma brain natriuretic peptide levels or elevated left ventricular filling pressure and thromboembolic risk in patients with non-valvular atrial fibrillation.

    PubMed

    Yu, Ga-In; Cho, Kyoung-Im; Kim, Hyun-Su; Heo, Jung-Ho; Cha, Tae-Joon

    2016-08-01

    We aimed to investigate the role of brain natriuretic peptide (BNP) levels and left ventricular (LV) filling pressures in thromboembolic risk in patients with non-valvular atrial fibrillation (AF). Among 327 patients with non-valvular AF, the ratio of peak early filling velocity to mitral annulus velocity (E/Ea) and N-terminal proBNP (NT-proBNP) was compared according to the presence of left atrial appendage (LAA) dysfunction [presence of spontaneous echo contrast (SEC)≥grade 3 and/or reduced LAA emptying flow velocity <20cm/s]. Compared to patients without LAA dysfunction, patients with LAA dysfunction presented with significantly higher CHADS2 scores (1.24±1.14 vs. 1.68±1.31, p=0.005), high-sensitivity C-reactive protein (0.36±1.18mg/dl vs. 0.66±1.32mg/dl, p=0.043), and NT-proBNP (765.3±2534.8pg/ml vs. 2266.9±6117.4pg/ml, p=0.002). Furthermore, patients with LAA dysfunction showed significantly higher left atrial volume index (LAVI, 25.1±10.9 vs. 43.1±22.1, p<0.001) and E/Ea (10.8±7.27 vs. 7.97±2.50mg/dl, p<0.001). Plasma logNT-proBNP levels were significantly correlated with the presence of SEC (r=0.276, p<0.001), LAA emptying flow velocity (r=-0.492, p<0.001), LAVI (r=0.405, p<0.001), and E/Ea (r=0.353, p<0.001). Binary logistic regression analysis showed that high NT-proBNP level >249.7pg/ml (odds ratio, OR 6.79, 95% confidence interval, CI 3.16-15.55, p<0.001) and E/Ea >10 (OR 4.41, 95% CI 2.39-8.15, p<0.001) were independent predictors of LAA dysfunction after adjustment of known thromboembolic risk factors. Elevated plasma NT-proBNP concentrations and LV filling pressures represented by LAA dysfunction may be reliable surrogate markers for predicting thromboembolic risk in patients with AF. Copyright © 2016. Published by Elsevier Ltd.

  11. Atrial natriuretic peptide down-regulates LPS/ATP-mediated IL-1β release by inhibiting NF-kB, NLRP3 inflammasome and caspase-1 activation in THP-1 cells.

    PubMed

    Mezzasoma, Letizia; Antognelli, Cinzia; Talesa, Vincenzo Nicola

    2016-02-01

    Atrial natriuretic peptide (ANP) is an hormone/paracrine/autocrine factor regulating cardiovascular homeostasis by guanylyl cyclase natriuretic peptide receptor (NPR-1). ANP plays an important role also in regulating inflammatory and immune systems by altering macrophages functions and cytokines secretion. Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine involved in a wide range of biological responses, including the immunological one. Unlike other cytokines, IL-1β production is rigorously controlled. Primarily, NF-kB activation is required to produce pro-IL-1β; subsequently, NALP3 inflammasome/caspase-1 activation is required to cleave pro-IL-1β into the active secreted protein. NALP3 is a molecular platform capable of sensing a large variety of signals and a major player in innate immune defense. Due to their pleiotropism, IL-1β and NALP3 dysregulation is a common feature of a wide range of diseases. Therefore, identifying molecules regulating IL-1β/NALP3/caspase-1 expression is an important step in the development of new potential therapeutic agents. The aim of our study was to evaluate the effect of ANP on IL-1β/NALP3/caspase-1 expression in LPS/ATP-stimulated human THP1 monocytes. We provided new evidence of the direct involvement of ANP/NPR-1/cGMP axis on NF-kB/NALP3/caspase-1-mediated IL-1β release and NF-kB-mediated pro-IL-1β production. In particular, ANP inhibited both NF-kB and NALP3/caspase-1 activation leading to pro- and mature IL-1β down-regulation. Our data, pointing out a modulatory role of this endogenous peptide on IL-1β release and on NF-kB/NALP3/caspase-1 activation, indicate an important anti-inflammatory and immunomodulatory effect of ANP via these mechanisms. We suggest a possible employment of ANP for the treatment of inflammatory/immune-related diseases and IL-1β/NALP3-associated disorders, affecting millions of people worldwide.

  12. Galectin-3 as a marker of interstitial atrial remodelling involved in atrial fibrillation

    PubMed Central

    Hernández-Romero, Diana; Vílchez, Juan Antonio; Lahoz, Álvaro; Romero-Aniorte, Ana I.; Jover, Eva; García-Alberola, Arcadio; Jara-Rubio, Rubén; Martínez, Carlos M.; Valdés, Mariano; Marín, Francisco

    2017-01-01

    Remodelling in the atria could appear as a result of hypertension, diabetes or ischaemic heart disease. Galectin-3 (Gal-3) is a mediator of profibrotic pathways and a potential biomarker of cardiac remodelling. We prospectively recruited consecutive patients undergoing elective cardiac surgery. Preoperative Gal-3 levels were determined from serum samples, and the presence of fibrosis was assessed from atrial appendage tissue samples obtained during cardiac surgery. We included 100 patients with aortic valve or ischaemic heart diseases and 15 controls with permanent AF. Gal-3 levels were associated with sex, left atrial volume, previous cardiac disease, diabetes mellitus, hypertension, NYHA and NT-proBNP. We observed differences in serum Gal-3 concentrations between patients and controls with permanent AF (p = 0.020). We performed ROC curves related to fibrosis and established a cutoff point for Gal-3 >13.65 ng/ml. Multivariate analyses showed previous cardiac disease, NYHA scale and high Gal-3 to be independent predictors of fibrosis. After adjustment for confounding factors, atrial fibrosis remained the only independent factor for the development of AF (p = 0.022). High Gal-3 serum levels predict fibrosis of the atrial appendage. NYHA scale and previous cardiac disease were also associated with tissue fibrosis in patients undergoing surgery. Atrial fibrosis was the only independent predictor for post-operative AF occurrence in our model after correcting for confounding factors. PMID:28079145

  13. IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells.

    PubMed

    Chu, Chun-Hsien; Tzang, Bor-Show; Chen, Li-Mien; Kuo, Chia-Hua; Cheng, Yi-Chang; Chen, Ling-Yun; Tsai, Fuu-Jen; Tsai, Chang-Hai; Kuo, Wei-Wen; Huang, Chih-Yang

    2008-05-01

    The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. In our previous studies, we detected an increased expression of IGF-II and IGF2R in cardiomyocytes that had undergone pathological hypertrophy. We hypothesized that after binding with IGF-II, IGF2R may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. In this study, we used immunohistochemical analysis of the human cardiovascular tissue array to detect expression of IGF2R. In our study of H9c2 cardiomyoblast cell cultures, we used the rhodamine phalloidin staining to measure the cell hypertrophy and western blot to measure the expression of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. We found that a significant association between IGF2R overexpression and myocardial infarction. The treatment of H9c2 cardiomyoblast cells with IGF-II not only induced cell hypertrophy but also increased the protein level of ANP and BNP. Using Leu27IGF-II, an analog of IGF-II which interacts selectively with the IGF2R, to specifically activate IGF2R signaling cascades, we found that binding of Leu27IGF-II to IGF2R led to an increase in the phosphorylation of protein Kinase C (PKC)-alpha and calcium/calmodulin-dependent protein kinase II (CaMKII) in a Galphaq-dependent manner. By the inhibition of PKC-alpha/CaMKII activity, we found that IGF-II and Leu27IGF-II-induced cell hypertrophy and upregulation of ANP and BNP were significantly suppressed. Taken together, this study provides a new insight into the effects of the IGF2R and its downstream signaling in cardiac hypertrophy. The suppression of IGF2R signaling pathways may be a good strategy to prevent the progression of pathological hypertrophy.

  14. Plasma B-type Natriuretic Peptide as a Predictor of Cardiovascular Events in Subjects with Atrial Fibrillation: A Community-Based Study

    PubMed Central

    Nakamura, Motoyuki; Koeda, Yorihiko; Tanaka, Fumitaka; Onoda, Toshiyuki; Itai, Kazuyoshi; Ohsawa, Masaki; Tanno, Kozo; Sakata, Kiyomi; Omama, Shinich; Ishibashi, Yasuhiro; Makita, Shinji; Ohta, Mutsuko; Ogasawara, Kuniaki; Komatsu, Takashi; Okayama, Akira

    2013-01-01

    Objectives Atrial fibrillation (AF) is a significant public health issue due to its high prevalence in the general population, and is associated with an increased risk of cardiovascular (CV) events including systemic thrombo-embolism, heart failure, and coronary artery disease. The relationship between plasma B-type natriuretic peptide (BNP) and CV risk in real world AF subjects remains unknown. Methods The subject of the study (n = 228; mean age = 69 years) was unselected individuals with AF in a community-based population (n = 15,394; AF prevalence rate = 1.5%). The CV event free rate within each BNP tertile was estimated, and Cox regression analysis was performed to examine the relative risk of the onset of CV events among the tertiles. The prognostic ability of BNP was compared to an established risk score for embolic events (CHADS2 score). In addition, to determine the usefulness of BNP as a predictor in addition to CHADS2 score, we calculated Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) indices. Results During the follow-up period 58 subjects experienced CV events (52 per 1,000 person-years). The event-free ratio was significantly lower in the highest tertile (p < 0.02). After adjustment for established CV risk factors, the hazard ratio (HR) of the highest tertile was significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02). The predictive abilities of plasma BNP in terms of sensitivity and specificity for general CV events were comparable to those of CHADS2 score. Adding BNP to the CHADS2 score only model improved the NRI (0.319; p < 0.05) and the IDI (0.046; p < 0.05). Conclusion Plasma BNP is a valuable biomarker both singly or in combination with an established scoring system for assessing general CV risk including stroke, heart failure and acute coronary syndrome in real-world AF subjects. PMID:24312541

  15. Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

    PubMed

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei; Kangawa, Kenji

    2017-02-07

    Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

  16. Atrial natriuretic peptide: A novel mediator for TGF-β1-induced epithelial-mesenchymal transition in 16HBE-14o and A549 cells.

    PubMed

    Chu, Shuyuan; Zhang, Xiufeng; Sun, Yabing; Yu, Yuanyuan; Liang, Yaxi; Jiang, Ming; Huang, Jianwei; Ma, Libing

    2017-02-13

    Atrial natriuretic peptide (ANP) is increasingly expressed on airway and inhibits pulmonary arterial remodeling. However, the role of ANP in remodeling of respiratory system is still unclear. The role of ANP on airway remodeling and the possible mechanism was explored in this study. Both human bronchial epithelial 16HBE-14o cells and alveolar epithelial A549 cells were stimulated by TGF-β1, ANP, cGMP inhibitor, PKG inhibitor, and cGMP analogue. The expressions of epithelial markers, mesenchymal markers, and Smad3 were assessed by quantitative real-time PCR and western blotting. Immunohistochemical staining was employed to assess Smad3 expression once it was silenced by siRNA in 16HBE-14o or A549 cells. Our results showed that the mRNA and protein expressions of E-Cadherin were decreased, whereas α-SMA expressions were increased after induction by TGF-β1 in 16HBE-14o and A549 cells. The E-Cadherin expressions were increased and α-SMA expressions were decreased after ANP stimulation. Inhibition of cGMP or PKG decreased E-Cadherin expression but increased α-SMA expression, which could be reversed by cGMP analogue. Moreover, the phosphorylated Smad3 expression was consistent with α-SMA expression. After smad3 was silenced, Smad3 was mostly expressed in cytoplasm instead of nucleus as non-silenced cells during epithelial-mesenchymal transition (EMT). In conclusion, ANP inhibits TGF-β1-induced EMT in 16HBE-14o and A549 cells through cGMP/PKG signaling, by which it targets TGF-β1/Smad3 via attenuating phosphorylation of Smad3. These findings suggest the potential of ANP in the treatment on pulmonary diseases with airway remodeling.

  17. Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

    PubMed Central

    Cody, R J; Atlas, S A; Laragh, J H; Kubo, S H; Covit, A B; Ryman, K S; Shaknovich, A; Pondolfino, K; Clark, M; Camargo, M J

    1986-01-01

    We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF. Images PMID:2945832

  18. Relationship between Doppler transmitral flow velocity pattern and plasma atrial and brain natriuretic peptide concentrations in anuric patients on maintenance hemodialysis.

    PubMed

    Ito, Shigenori; Murai, Sumiko; Takada, Norio; Ozasa, Atsushi; Hanada, Mayumi; Sugiyama, Masaya; Suzuki, Kaoru; Nagae, Yuji; Inagaki, Toshiaki; Takeda, Yutaka; Fukutomi, Tatsuya; Joh, Takashi

    2006-05-01

    Plasma atrial (ANP) and brain (BNP) natriuretic peptide levels were compared to determine if transmitral flow velocity pattern is an instantaneous marker of body fluid balance in anuric patients on hemodialysis (HD). We measured plasma ANP and BNP levels and performed Doppler echocardiography in 38 anuric patients before and after HD. Patients with valvular disease, left ventricular systolic dysfunction having a fractional shortening < 0.3, arrhythmia, or left ventricular hypertrophy were excluded. The relationships between plasma ANP or BNP levels and the transmitral flow velocity pattern were evaluated. We also determined if the magnitude of the decrease in plasma ANP level was related to that in the early peak of transmitral flow velocity (peak E). The mean age of the subjects was 61.1 +/- 9.7 years. The ANP level of 213.6 +/- 146.1 pg/mL was related to peak E of 61 +/- 15 cm/s before HD (R = 0.504, P < 0.001), but not after HD. Plasma ANP level was not related to peak late transmitral flow velocity (peak A) or peak E/peak A before or after HD. BNP level was not related to the transmitral flow velocity pattern. The magnitude of decrease in hANP level during HD was significantly related to that in peak E (R = 0.342, P < 0.05). Before HD, peak E was related to the plasma ANP level, reflecting volume overload. Change in peak E showed a weak relationship with that of plasma ANP level in the same HD patient. The measurement of peak E during a HD session may potentially enable the assessment of hydration status during HD.

  19. Neonatal oxytocin treatment modulates oxytocin receptor, atrial natriuretic peptide, nitric oxide synthase and estrogen receptor mRNAs expression in rat heart

    PubMed Central

    Pournajafi-Nazarloo, Hossein; Perry, Adam; Partoo, Leila; Papademeteriou, Eros; Azizi, Feridoun; Carter, C. Sue; Cushing, Bruce S.

    2007-01-01

    Oxytocin (OT) has been implicated in reproductive functions, induction of maternal behavior as well as endocrine and neuroendocrine regulation of the cardiovascular system. Here we demonstrate that neonatal manipulation of OT can modulate the mRNAs expression for OT receptor (OTR), atrial natriuretic peptide (ANP), endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERα) in the heart. On the first day of postnatal life, female and male rats were randomly assigned to receive one of following treatments; (a) 50 µl i.p. injection of 7 µg OT, (b) 0.7 µg of OT antagonist (OTA), or (c) isotonic saline (SAL). Hearts were collected either on postnatal day 1 or day 21 (D1 or D21) and the mRNAs expression of OTR, ANP, inducible NOS (iNOS), eNOS, ERα and estrogen receptor beta (ERβ) were compared by age, treatment, and sex utilizing Real Time PCR. OT treatment significantly increased heart OTR, ANP and eNOS mRNAs expression on D1 in both males and females, ERα increased only in females. While there were significant changes in the relative expression of all types of mRNA between D1 and D21 there were no significant treatment effects observed in D21 animals. OTA treatment significantly decreased basal ANP and eNOS mRNAs expression on D1 in both sexes. The results indicate that during the early postnatal period OT can have an immediate effect on the expression OTR, ANP, eNOS, and ERα mRNAs and that these effects are mitigated by D21. Also with the exception of ERα mRNA, the effects are the same in both sexes. PMID:17537544

  20. Reversibly Bound Chloride in the Atrial Natriuretic Peptide Receptor Hormone Binding Domain: Possible Allosteric Regulation and a Conserved Structural Motif for the Chloride-binding Site

    SciTech Connect

    Ogawa, H.; Qiu, Y; Philo, J; Arakawa, T; Ogata, C; Misono, K

    2010-01-01

    The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.

  1. Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

    PubMed

    Shaikh, Amir Y; Esa, Nada; Martin-Doyle, William; Kinno, Menhel; Nieto, Iryna; Floyd, Kevin C; Browning, Clifford; Ennis, Cynthia; Donahue, J Kevin; Rosenthal, Lawrence S; McManus, David D

    2015-12-01

    Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI (>3 months post-PVI) over the 6-month follow-up period. A BNP greater than or equal to 100 pg/dL (P=0.01) and AF recurrence within 3 months after PVI (P<0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P=0.001) and a net reclassification improvement of 60% (P=0.001) for all risk scores. Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence.

  2. Recombinant Atrial Natriuretic Peptide Prevents Aberrant Ca2+ Leakage through the Ryanodine Receptor by Suppressing Mitochondrial Reactive Oxygen Species Production Induced by Isoproterenol in Failing Cardiomyocytes

    PubMed Central

    Susa, Takehisa; Nanno, Takuma; Ishiguchi, Hironori; Myoren, Takeki; Nishimura, Shigehiko; Kato, Takayoshi; Hino, Akihiro; Oda, Tetsuro; Okuda, Shinichi; Yamamoto, Takeshi; Yano, Masafumi

    2016-01-01

    Catecholamines induce intracellular reactive oxygen species (ROS), thus enhancing diastolic Ca2+ leakage through the ryanodine receptor during heart failure (HF). However, little is known regarding the effect of atrial natriuretic peptide (ANP) on ROS generation and Ca2+ handling in failing cardiomyocytes. The aim of the present study was to clarify the mechanism by which an exogenous ANP exerts cardioprotective effects during HF. Cardiomyocytes were isolated from the left ventricles of a canine tachycardia-induced HF model and sham-operated vehicle controls. The degree of mitochondrial oxidized DNA was evaluated by double immunohistochemical (IHC) staining using an anti-VDAC antibody for the mitochondria and an anti-8-hydroxy-2′-deoxyguanosine antibody for oxidized DNA. The effect of ANP on ROS was investigated using 2,7-dichlorofluorescin diacetate, diastolic Ca2+ sparks assessed by confocal microscopy using Fluo 4-AM, and the survival rate of myocytes after 48 h. The double IHC study revealed that isoproterenol (ISO) markedly increased oxidized DNA in the mitochondria in HF and that the ISO-induced DNA damage was markedly inhibited by the co-presence of ANP. ROS production and Ca2+ spark frequency (CaSF) were increased in HF compared to normal controls, and were further increased in the presence of ISO. Notably, ANP significantly suppressed both ISO-induced ROS and CaSF without changing sarcoplasmic reticulum Ca2+ content in HF (p<0.01, respectively). The survival rate after 48 h in HF was significantly decreased in the presence of ISO compared with baseline (p<0.01), whereas it was significantly improved by the co-presence of ANP (p<0.01). Together, our results suggest that ANP strongly suppresses ISO-induced mitochondrial ROS generation, which might correct aberrant diastolic Ca2+ sparks, eventually contributing to the improvement of cardiomyocyte survival in HF. PMID:27657534

  3. Effects of immobilizations stress with or without water immersion on the expression of atrial natriuretic peptide in the hearts of two rat strains

    PubMed Central

    Slavikova, Jana; Mistrova, Eliska; Klenerova, Vera; Kruzliak, Peter; Caprnda, Martin; Hynie, Sixtus; Sida, Pavel; Dvorakova, Magdalena Chottova

    2016-01-01

    Atrial natriuretic peptide (ANP) is produced and released by mammalian cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure. The present study examined localization of ANP and a possible role of the hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used. The animals were exposed to the two types of stress: immobilization and immobilization combined with water immersion for 1 hour. Localization of ANP was detected by immunohistochemistry and expression of the proANP mRNA by real-time qPCR in all heart compartments of control and stressed animals after 1 and 3 hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high density of ANP-immunoreactivity was observed in both atria of both rat strains. In control rats of both strains, the expression of the proANP mRNA was higher in the atria than in ventricles. In SD rats with the intact HPA axis, an upregulation of ANP gene expression was observed in the right atrium after IS1, in both atria and the left ventricle after IS3 and in the left atrium and the left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis, no increase or even a downregulation of the gene expression was observed. Thus, acute stress-induced increase in the expression of the proANP gene is related to the activity of the HPA axis. It may have relevance to ANP-induced protection of the heart. PMID:27508036

  4. Usefulness of early diastolic mitral annular velocity to predict plasma levels of brain natriuretic peptide and transient heart failure development after device closure of atrial septal defect.

    PubMed

    Masutani, Satoshi; Taketazu, Mio; Mihara, Chihiro; Mimura, Yuko; Ishido, Hirotaka; Matsunaga, Tamotsu; Kobayashi, Toshiki; Senzaki, Hideaki

    2009-12-15

    Device closure of atrial septal defect (ASD) is sometimes followed by elevation of plasma brain natriuretic peptide (BNP), a marker of heart failure, and progression to heart failure. This study tested the hypothesis that the underlying diastolic dysfunction, assessed on tissue Doppler images (TDI) before device closure, can predict BNP level after ASD closure. The study subjects were 39 consecutive patients (age 27.5 +/- 16.3 years, range 5 to 63) who underwent device closure for ASD. Echocardiographic evaluation using TDI and 2-dimensional and pulse wave Doppler were performed, together with plasma BNP measurement 1 day before and 2 days after ASD closure. Before ASD closure, an age-dependent decrease was noted in left ventricular relaxation, assessed by early diastolic mitral annular velocity. ASD closure resulted in a decrease in early diastolic mitral annular velocity (from 14.7 to 12.3 cm/s, p <0.05) despite an increase in the left ventricular dimension (84% to 92% vs normal, p <0.05). These changes were associated with a parallel increase in BNP (17.9 to 48.4 pg/ml, p <0.05). Stepwise multivariate linear regression identified early diastolic mitral annular velocity before ASD closure and age as independent predictors of BNP levels after ASD closure (p <0.05). Consistent with this result, 2 patients with the lowest early diastolic mitral annular velocity developed exertional dyspnea after the procedure. In conclusion, our results indicate that TDI measurements could be useful to detect underlying diastolic dysfunction that can potentially cause heart failure after ASD closure and emphasize the importance of ASD closure at a young age before impairment of left ventricular relaxation.

  5. Analytical performance and clinical usefulness of a commercially available IRMA kit for measuring atrial natriuretic peptide in patients with heart failure.

    PubMed

    Clerico, A; Iervasi, G; Del Chicca, M G; Maffei, S; Berti, S; Sabatino, L; Turchi, S; Cazzuola, F; Manfredi, C; Biagini, A

    1996-10-01

    We evaluated the analytical characteristics and clinical usefulness of a commercially available IRMA kit for measuring plasma concentrations of atrial natriuretic peptide (ANP) in healthy subjects and in patients with heart failure. The method uses two monoclonal antibodies prepared against sterically remote epitopes of the ANP molecule; the first antibody is coated on the solid-phase beads, and the second is radiolabeled with 125I. Fifty-nine healthy subjects and 77 patients with heart failure were studied. After subjects had rested 20 min in a recumbent position, blood samples were collected from a brachial vein into ice-chilled disposable polypropylene tubes containing aprotinin and EDTA. Plasma samples were immediately separated by centrifugation and stored at -20 degrees C until assay. The working range (CV <15%) was 10-2000 ng/L. The detection limit (2.13 +/- 0.91 ng/L) was similar to those reported for other IRMAs but was much better than those of RIAs. For healthy subjects, the results of this method (18.0 +/- 10.6 ng/L, range 4.7-63 ng/L, median 16.7 ng/L, n = 59) were similar to those generally reported for the most accurate methods, i.e., those using preliminary extraction and chromatographic purification of plasma samples. Measured plasma ANP was significantly associated with the severity of clinical symptoms, i.e., NYHA class (ANOVA, P <0.0001), and with the left ventricular ejection fraction (n = 62, r = 0.618, P <0.0001). Patients with severe heart failure showed greatly increased values (NYHA III-IV: 257.4 +/- 196.6 ng/L, n = 23).

  6. Modulation in Natriuretic Peptides System in Experimental Colitis in Rats.

    PubMed

    Lee, Chang Ho; Ha, Gi Won; Kim, Jong Hun; Kim, Suhn Hee

    2016-04-01

    Renin-angiotensin system is involved in the pathophysiology of colonic inflammation. However, there are a few reports about modulation of natriuretic peptide system. This study investigates whether a local atrial natriuretic peptide (ANP) system exists in rat colon and whether ANP plays a role in the regulation of colonic motility in experimental colitis rat model. Experimental colitis was induced by an intake of 5 % dextran sulfate sodium (DSS) dissolved in tap water for 7 days. After rats were killed, plasma hormone concentrations and mRNAs for natriuretic peptide system were measured. Functional analysis of colonic motility in response to ANP was performed using taenia coli. DSS-treated colon showed an increased necrosis with massive infiltration of inflammatory cells. The colonic natriuretic peptide receptor-A mRNA level and particulate guanylyl cyclase activity in response to ANP from colonic tissue membranes were higher, and the mRNA levels of ANP and natriuretic peptide receptor-B were lower in DSS-treated rats than in control rats. ANP decreased the frequency of basal motility in a dose-dependent manner but did not change the amplitude. The inhibitory responses of frequency of basal motility to ANP and 8-bromo-cGMP were enhanced in DSS-treated rat colon. In conclusion, augmentation of inhibitory effect on basal motility by ANP in experimental colitis may be due an increased expression of colonic natriuretic peptide receptor-A mRNA. These data suggest that local natriuretic peptide system is partly involved in the pathophysiology of experimental colitis.

  7. Right Ventricular and Right Atrial Involvement Can Predict Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy?

    PubMed

    Doesch, Christina; Lossnitzer, Dirk; Rudic, Boris; Tueluemen, Erol; Budjan, Johannes; Haubenreisser, Holger; Henzler, Thomas; Schoenberg, Stefan O; Borggrefe, Martin; Papavassiliu, Theano

    2016-01-01

    Atrial fibrillation (AF) is associated with clinical deterioration, stroke and disability in patients with hypertrophic cardiomyopathy (HCM). Therefore, the objective of this study was to evaluated cardiac magnetic resonance (CMR)-derived determinants for the occurrence of AF in patients with HCM. 98 Patients with HCM and 30 healthy controls underwent CMR and were followed-up for 6 ± 3 years. 19 (19.4%) patients presented with AF at initial diagnosis, 19 (19.4%) developed AF during follow-up and 60 (61.2%) remained in sinus rhythm (SR). Compared to healthy controls, patients with HCM who remained in SR presented with significantly increased left ventricular mass, an elevated left ventricular remodeling index, enlarged left atrial volumes and reduced septal mitral annular plane systolic excursion (MAPSE) compared to healthy controls. Whereas HCM patients who presented with AF at initial diagnosis and those who developed AF during follow-up additionally presented with reduced tricuspid annular plane systolic excursion (TAPSE) and right atrial (RA) dilatation. Receiver-operator curve analysis indicated good predictive performance of TAPSE, RA diameter and septal MAPSE (AUC 0.73, 0.69 and 0.71, respectively) to detect patients at risk of developing AF. Reduced MAPSE measurements and enlarged LA volumes seems to be a common feature in patients with HCM, whereas reduced TAPSE and RA dilatation only seem to be altered in patients with history of AF and those developing AF. Therefore, they could serve as easy determinable markers of AF in patients with HCM.

  8. Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2

    PubMed Central

    Klaiber, Michael; Kruse, Martin; Völker, Katharina; Schröter, Juliane; Feil, Robert; Freichel, Marc; Gerling, Andrea; Feil, Susanne; Dietrich, Alexander; Londoño, Juan Eduardo Camacho; Baba, Hideo A.; Abramowitz, Joel; Birnbaumer, Lutz; Penninger, Josef M.; Pongs, Olaf

    2010-01-01

    Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but the downstream signalling pathways are unknown. Here, we examined the influence of ANP on β-adrenergic versus Angiotensin II (Ang II)-dependent (Gs vs. Gαq mediated) modulation of Ca2+i-handling in cardiomyocytes and of hypertrophy in intact hearts. L-type Ca2+ currents and Ca2+i transients in adult isolated murine ventricular myocytes were studied by voltage-clamp recordings and fluorescence microscopy. ANP suppressed Ang II-stimulated Ca2+ currents and transients, but had no effect on isoproterenol stimulation. Ang II suppression by ANP was abolished in cardiomyocytes of mice deficient in GC-A, in cyclic GMP-dependent protein kinase I (PKG I) or in the regulator of G protein signalling (RGS) 2, a target of PKG I. Cardiac hypertrophy in response to exogenous Ang II was significantly exacerbated in mice with conditional, cardiomyocyte-restricted GC-A deletion (CM GC-A KO). This was concomitant to increased activation of the Ca2+/calmodulin-dependent prohypertrophic signal transducer CaMKII. In contrast, β-adrenoreceptor-induced hypertrophy was not enhanced in CM GC-A KO mice. Lastly, while the stimulatory effects of Ang II on Ca2+-handling were absent in myocytes of mice deficient in TRPC3/TRPC6, the effects of isoproterenol were unchanged. Our data demonstrate a direct myocardial role for ANP/GC-A/cGMP to antagonize the Ca2+i-dependent hypertrophic growth response to Ang II, but not to β-adrenergic stimulation. The selectivity of this interaction is determined by PKG I and RGS2-dependent modulation of Ang II/AT1 signalling. Furthermore, they strengthen published observations in neonatal cardiomyocytes showing that TRPC3/TRPC6 channels are essential for Ang II, but not for β-adrenergic Ca2+i-stimulation in adult myocytes. PMID:20352235

  9. THE ATRIAL NATRIURETIC PEPTIDE GENETIC VARIANT RS5065 AND RISK FOR CARDIOVASCULAR DISEASE IN THE GENERAL COMMUNITY: A NINE-YEAR FOLLOW-UP STUDY RR

    PubMed Central

    Cannone, Valentina; Huntley, Brenda; Olson, Timothy M.; Heublein, Denise M.; Scott, Christopher; Bailey, Kent R.; Redfield, Margaret M.; Rodeheffer, Richard J.; Burnett, John C.

    2014-01-01

    We analyzed the phenotype associated with the atrial natriuretic peptide (ANP) genetic variant rs5065 in a random community-based sample. We also assessed and compared the biological action of two concentrations (10−10 mol/L, 10−8 mol/L) of ANP and ANP-RR, the protein variant encoded by the minor allele of rs5065, on activation of the guanylyl cyclase-A (GC-A) and B (GC-B) receptors, production of the second messenger 3’,5’cyclic guanosine monophosphate (cGMP) in endothelial cells and endothelial permeability. Rs5065 genotypes were determined in a cross-sectional adult cohort from Olmsted County, MN (n=1623). Genotype frequencies for rs5065 were 75%, 24%, and 1% for TT, TC and CC, respectively. Multivariate analysis showed that the C allele was associated with increased risk of cerebrovascular accident (hazard ratio 1.43; 95% CI, 1.09 to 1.86; p= 0.009) and higher prevalence of myocardial infarction (odd ratio = 1.82; 95% CI, 1.07 to 3.09; p= 0.026). ANP-RR 10−8mol/L activated the GC-A receptor (83.07 ±8.31 vs no treatment 0.18±0.04 6-per well, p=0.006), ANP-RR 10−10mol/L did not. Neither 10−8mol/L nor 10−10mol/L ANP-RR activated GC-B receptor (p=0.10, p= 0.35). ANP 10−8mol/L and ANP-RR 10−8mol/L stimulated cGMP production in endothelial cells similarly (p=0.58). Both concentrations of ANP-RR significantly enhanced human aortic endothelial cell permeability (69 vs 29 RFUs, p=0.012; 58 vs 39 RFUs, p= 0.015) compared to ANP. The minor allele of rs5065 was associated with increased cardiovascular risk. ANP-RR activated the GC-A receptor, increased cGMP in endothelial cells and when compared to ANP, ANP-RR augmented endothelial cell permeability. PMID:24041948

  10. Evaluation of exercise capacity with cardiopulmonary exercise testing and type B natriuretic peptide concentrations in adult patients with patent atrial septal defect.

    PubMed

    Trojnarska, Olga; Szyszka, Andrzej; Gwizdala, Adrian; Oko-Sarnowska, Zofia; Katarzynski, Slawomir; Siniawski, Andrzej; Chmara, Ewa; Cieslinski, Andrzej

    2006-01-01

    Adults with patent atrial septal defect (ASD) usually find their exercise capacity satisfactory, and therefore hesitate to accept proposed surgical treatment of the heart disease. The aim of our study was to evaluate both the exercise capacity, using the cardio-pulmonary stress test, and brain natriuretic peptide (BNP) levels in asymptomatic adults with ASD. Thirty-six patients with patent secundum type ASD (aged mean 44.7 +/- 8.2 years) were studied. The control group consisted of 25 healthy subjects at the mean age of 45.6 +/- 6.1 years. Echocardiography and CPST were performed and BNP levels measured in all subjects. Oxygen uptake (VO2 max) was lower in ASD patients than in controls (22.1 +/- 5.6 vs. 30.0 +/- 6.8 ml/kg/min, p = 0.00001); the VE/VO2 slope was elevated in ASD patients compared with healthy subjects (31.3 +/- 6.6 vs. 26.9 +/- 3.3, p = 0.001), and exceeded 34 in 5 patients. VO2 max showed a negative correlation with the pulmonary to systemic flow ratio Qp:Qs (r = -0.46, p = 0.004), and a positive correlation was found between the VE/VO2 slope and Qp:Qs (r = 0.32, p = 0.05). BNP levels were higher in the ASD group than in the controls (60.6 +/- 49.9 vs. 32.6 +/- 24.5 pg/ml, p = 0.02). BNP correlated positively with RV diameter and Qp:Qs (r = 0.38 and 0.39 respectively, p = 0.03) and negatively with maximum VO2 (r = -0.5, p = 0.004) and VO2% (r = -0.32, p = 0.07). Although most adult patients with ASD perceive their exercise capacity as satisfactory, objective assessment reveals that in fact it is significantly decreased. BNP levels are increased comparing to healthy individuals. Decreased exercise capacity and increased BNP levels seem to result from right ventricular volume overload. Copyright 2006 S. Karger AG, Basel.

  11. Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts. Immunohistochemical study of the endomyocardial biopsy specimens.

    PubMed

    Takemura, G; Fujiwara, H; Horike, K; Mukoyama, M; Saito, Y; Nakao, K; Matsuda, M; Kawamura, A; Ishida, M; Kida, M

    1989-11-01

    To investigate the mechanism of expression of atrial natriuretic polypeptide (ANP) in human ventricles, we conducted an immunohistochemical study of ANP in biventricular endomyocardial biopsy specimens obtained from a total of 49 patients with cardiac dilatation due to dilated cardiomyopathy (21 patients), postmyocarditis (18 patients), or volume overload (five patients) and subjects with no dilatation as controls (five patients). Four-micron thick sections were stained by an indirect immunoperoxidase method using monoclonal antibody to alpha-human ANP as the primary antibody. The frequency of ANP-present myocytes was calculated in each specimen and compared with clinical, echocardiographic, hemodynamic, angiographic, and histologic parameters. ANP-present myocytes were noted in all of the 21 patients with dilated cardiomyopathy, in 11 of the 18 patients with postmyocarditis, in four of the five patients with volume overload, and in zero of the five controls. The mean percentage of ANP-present myocytes was significantly greater in the left-side specimens (35 +/- 37%) than in the right-side ones (2 +/- 4%). The percentage of ANP-present myocytes in the left-side specimens significantly correlated with peak systolic or end-diastolic wall stress (r = 0.67 and 0.58), left ventricular end-systolic or end-diastolic volume index (r = 0.75 and 0.69), or left ventricular end-diastolic pressure (r = 0.42) and inversely correlated with ejection fraction (r = -0.73), systolic left ventricular wall thickness (r = -0.58), or cardiac index (r = -0.30). Expression of ANP was rarely seen in the cases with normal wall stresses, normal ejection fraction, normal volume, or normal myocyte size. However, it was seen frequently even in hearts with normal levels of left ventricular end-diastolic pressure and cardiac index (compensated hearts). The percent of ANP-present myocytes in both sides significantly correlated with size of myocytes (r = 0.48 at right and r = 0.57 at left side) or

  12. Serum atrial natriuretic peptide (ANP) as an objective indicator for the diagnosis of neurogenic shock: animal experiment and human case report.

    PubMed

    Zhao, Min-Zhu; Li, Yong-Guo; Zhang, Peng; Xiong, Jin-Cheng; Zhu, Shi-Sheng; Xiao, Xuan; Li, Jian-Bo

    2017-03-01

    In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group (n = 8), survival group (n = 15) and death group (n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult (P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult (P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo (P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock.

  13. Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation.

    PubMed

    White, R E; Lee, A B; Shcherbatko, A D; Lincoln, T M; Schonbrunn, A; Armstrong, D L

    1993-01-21

    Natriuretic peptides inhibit the release and action of many hormones through cyclic guanosine monophosphate (cGMP), but the mechanism of cGMP action is unclear. In frog ventricular muscle and guinea-pig hippocampal neurons, cGMP inhibits voltage-activated Ca2+ currents by stimulating phosphodiesterase activity and reducing intracellular cyclic AMP; however, this mechanism is not involved in the action of cGMP on other channels or on Ca2+ channels in other cells. Natriuretic peptide receptors in the rat pituitary also stimulate guanylyl cyclase activity but inhibit secretion by increasing membrane conductance to potassium. In an electrophysiological study on rat pituitary tumour cells, we identified the large-conductance, calcium- and voltage-activated potassium channels (BK) as the primary target of another inhibitory neuropeptide, somatostatin. Here we report that atrial natriuretic peptide also stimulates BK channel activity in GH4C1 cells through protein dephosphorylation. Unlike somatostatin, however, the effect of atrial natriuretic peptide on BK channel activity is preceded by a rapid and potent stimulation of cGMP production and requires cGMP-dependent protein kinase activity. Protein phosphatase activation by cGMP-dependent kinase could explain the inhibitory effects of natriuretic peptides on electrical excitability and the antagonism of cGMP and cAMP in many systems.

  14. Cyclical stretch induces structural changes in atrial myocytes.

    PubMed

    De Jong, Anne Margreet; Maass, Alexander H; Oberdorf-Maass, Silke U; De Boer, Rudolf A; Van Gilst, Wiek H; Van Gelder, Isabelle C

    2013-06-01

    Atrial fibrillation (AF) often occurs in the presence of an underlying disease. These underlying diseases cause atrial remodelling, which make the atria more susceptible to AF. Stretch is an important mediator in the remodelling process. The aim of this study was to develop an atrial cell culture model mimicking remodelling due to atrial pressure overload. Neonatal rat atrial cardiomyocytes (NRAM) were cultured and subjected to cyclical stretch on elastic membranes. Stretching with 1 Hz and 15% elongation for 30 min. resulted in increased expression of immediate early genes and phosphorylation of Erk and p38. A 24-hr stretch period resulted in hypertrophy-related changes including increased cell diameter, reinduction of the foetal gene program and cell death. No evidence of apoptosis was observed. Expression of atrial natriuretic peptide, brain natriuretic peptide and growth differentiation factor-15 was increased, and calcineurin signalling was activated. Expression of several potassium channels was decreased, suggesting electrical remodelling. Atrial stretch-induced change in skeletal α-actin expression was inhibited by pravastatin, but not by eplerenone or losartan. Stretch of NRAM results in elevation of stress markers, changes related to hypertrophy and dedifferentiation, electrical remodelling and cell death. This model can contribute to investigating the mechanisms involved in the remodelling process caused by stretch and to the testing of pharmaceutical agents.

  15. Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment.

    PubMed Central

    Omland, T.; Aakvaag, A.; Vik-Mo, H.

    1996-01-01

    OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction. RESULTS: Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and

  16. Natriuretic peptide drug leads from snake venom.

    PubMed

    Vink, S; Jin, A H; Poth, K J; Head, G A; Alewood, P F

    2012-03-15

    Natriuretic peptides are body fluid volume modulators, termed natriuretic peptides due to a role in natriuresis and diuresis. The three mammalian NPs, atrial natriuretic peptide (ANP), brain or b-type natriuretic peptide (BNP) and c-type natriuretic peptide (CNP), have been extensively investigated for their use as therapeutic agents for the treatment of cardiovascular diseases. Although effective, short half-lives and renal side effects limit their use. In approximately 30 years of research, NPs have been discovered in many vertebrates including mammals, amphibians, reptiles and fish, with plants and, more recently, bacteria also being found to possess NPs. Reptiles have produced some of the more interesting NPs, with dendroaspis natriuretic peptide (DNP), which was isolated from the venom of the green mamba (Dendroaspis angusticeps), having greater potency and increased stability as compared to the mammalian family members, and taipan natriuretic peptide c (TNPc), which was isolated from the venom of the inland taipan (Oxyuranus microlepidotus) displaying similar activity to ANP and DNP at rat natriuretic peptide receptor A. Although promising, more research is required in this field to develop therapeutics that overcome receptor-mediated clearance, and potential toxicity issues. This review investigates the use of snake venom NPs as therapeutic drug leads. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Myopericarditis with predominantly right ventricular involvement with normal B-type natriuretic peptide and cardiac tamponade as the initial manifestation of systemic lupus erythematosus.

    PubMed

    Manautou, Luis; Jerjes-Sanchez, Carlos; Meraz, Manuel; Perez-Garcia, Luis F; Diaz-Cid, Antonio; de la Peña-Almaguer, Erasmo; Avila, Cesar; Sanchez, Luis

    2014-08-01

    A previously healthy young man presented with a 12-hour history of sudden dyspnea and severe chest pain at rest. Initial findings of physical examination, electrocardiogram and chest radiography showed typical pericarditis and clinical instability. Echocardiogram revealed small pericardial effusion with right ventricle dilatation. The patient was admitted in the ICU; a new echocardiogram revealed moderate pericardial effusion and diagnosis of pericarditis complicated with acute cardiac tamponade was established. The patient transiently improved after pericardial window. In the following hours, the diagnosis of myocarditis with predominantly right ventricular involvement (MPRVI) with severe right heart failure was supported by clinical, chest radiography and echocardiogram data, despite normal B-type natriuretic peptide. On day 2, cardiac troponin I detection was observed. By day 3, B-type natriuretic peptide in the range of ventricular dysfunction was identified. Cardiovascular magnetic resonance findings supported the diagnosis of MPRVI. A systematic MEDLINE/PubMed from 1993 to 2013 does not identify any cases of MPRVI related to systemic lupus erythematosus. Simultaneous acute MPRVI with normal B-type natriuretic peptide and acute cardiac tamponade heralding the diagnosis of systemic lupus erythematosus, to the best of our knowledge, has not been previously described.

  18. Recombinant bovine growth hormone-induced reduction of atrial natriuretic peptide is associated with improved left ventricular contractility and reverse remodeling in cardiomyopathic UM-X7.1 hamsters with congestive heart failure.

    PubMed

    Mulumba, Mukandila; Céméus, Catia; Dumont, Louis; du Souich, Patrick; Ong, Huy; Marleau, Sylvie

    2007-04-01

    To assess the effect of short-term treatment with GH on left ventricular contractility and remodeling, after the development of heart failure in cardiomyopathic hamsters (CMH). Two groups of 200-day-old UM-X7.1 CMH received daily subcutaneous injections of recombinant bovine (rb) GH (1mg/kg/day) or 0.9% NaCl for 40 days. Golden Syrian hamsters (GSH) were used as controls. At 240-day-old, the hamsters were randomly subjected to (i) assessment of left ventricular systolic function in a Langendorff perfused mode followed by the determination of the passive diastolic pressure-volume relationship and morphometric measurements; (ii) assessment of left ventricular mRNA expression of genes belonging to the fetal gene program including atrial (ANP) and brain (BNP) natriuretic peptides and cardiac myosin heavy chain isoforms and of the circulating levels of the natriuretic peptides. Hearts from CMH were hypertrophied and dilated (p<0.05) compared to hearts from GSH, along with a approximately 10-fold increase in the circulating ANP and BNP levels. Left ventricular BNP and ANP mRNAs were elevated by 2- and 3-fold, respectively, compared to GSH. rbGH reduced both ANP mRNA and ANP circulating levels by 34% (p<0.01) but did not significantly modulate BNP levels. This effect was associated with a preserved systolic function and reverse remodeling as assessed by a leftward shift of the passive diastolic pressure-volume relationship indicating reduced ventricular dilatation. The data show that a short-term administration of GH in the terminal phase of the disease confers cardioprotection by attenuating systolic dysfunction and by inducing beneficial reverse remodeling.

  19. Correlation between plasma N-terminal pro-brain natriuretic peptide levels and changes in New York Heart Association functional class, left atrial size, left ventricular size and function after mitral and/or aortic valve replacement.

    PubMed

    Elasfar, Abdelfatah

    2012-01-01

    Elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in patients with chronic valvular disease. We designed the present study to assess whether changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after mitral, aortic and double mitral and aortic valve replacement reflect changes in heart failure (HF) symptoms including New York Heart Association (NYHA) class and changes in left atrium (LA) size, left ventricle (LV) size and LV function. A prospective observational nonrandomized study among consecutive patients undergoing mitral and/or aortic valve replacement in our center. The study population consisted of 24 patients (mean [SD] age of 55.3 [16.2] years, 58% were males) who underwent surgical mitral valve replacement (12 patients), aortic valve replacement (8 patients) and combined mitral and aortic valve replacement (4 patients). NT-proBNP measurements, transthoracic echocardiography and NYHA class assessments were performed before and 6 months after surgery. The decrease in NT-proBNP was associated with decrease in left atrial dimension (r = 0.73, P < .002), LV end-diastolic dimension (r=0.65, P=.001), LV end-systolic dimension (r=0.53, P=.036), and increase in ejection fraction (r=-0.65, P=.001) after 6 months postoperatively. Furthermore, a decreasing NT-proBNP was associated with improvement in NYHA class. NT-proBNP levels after mitral, aortic and double valve replacement correlates with changes in HF manifestations as well as changes in LA size and LV dimension and function. Thus, we hypothesize that interval measurement of the NT-proBNP level at clinic visits can allow early detection of any clinical deterioration as well as the possibility of assessment of the long-term outcome of those patients.

  20. A Butterfly-Shaped Primary Cardiac Lymphoma That Showed Bi-Atrial Involvement

    PubMed Central

    Cho, Jung Sun; Park, Mahn-Won; Kim, Hyoung Doo; Baek, Ju Yeal; Youn, Ho-Joong; Seung, Ki-Bae; Kim, Jae-Hyung

    2012-01-01

    We described here a patient who presented with symptoms of heart failure who was found to have severe bilateral impairment of atrioventricular inflow. Primary cardiac lymphoma (PCL) with extensive involvement of the two atria, pericardium and myocardium is an extremely rare tumor in immunocompetent patients. We report here a case of PCL in an immunocompetent patient with involvement of both atria and the atrial septum. The tumor had a butterfly shape. We could not do surgical excision because of the massive pericardiac invasion. The diagnosis was B-cell lymphoma and this was confirmed by the pericardiac biopsy. PMID:22363383

  1. Signaling Pathways Involved in Renal Oxidative Injury: Role of the Vasoactive Peptides and the Renal Dopaminergic System

    PubMed Central

    Rukavina Mikusic, N. L.; Kravetz, M. C.; Kouyoumdzian, N. M.; Della Penna, S. L.; Rosón, M. I.; Fernández, B. E.; Choi, M. R.

    2014-01-01

    The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation. PMID:25436148

  2. Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

    PubMed

    Claessens, Y-E; Schmidt, J; Batard, E; Grabar, S; Jegou, D; Hausfater, P; Kierzek, G; Guérin, S; Pourriat, J-L; Dhainaut, J-F; Ginsburg, C

    2010-06-01

    Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

  3. Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: a double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker.

    PubMed Central

    Sanderson, J. E.; Chan, W. W.; Hung, Y. T.; Chan, S. K.; Shum, I. O.; Raymond, K.; Woo, K. S.

    1995-01-01

    OBJECTIVES--This study examines the acute effects of two differing beta adrenergic blocking agents (metoprolol and a third generation vasodilating beta blocker) on plasma concentrations of atrial natriuretic factor (ANF), brain (ventricular) natriuretic factor (BNF), and haemodynamic variables in patients with heart failure. SETTING--University teaching hospital. METHODS--20 patients with impaired left ventricular systolic function [ejection fraction 32 (SEM 2.3)%] were randomised in a double blind manner to receive either oral metoprolol 6.25 mg twice daily or celiprolol 25 mg daily. Haemodynamic variables were evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF concentrations were measured at baseline, 5 h, and 24 h by radioimmunoassay. RESULTS--At baseline ANF and BNF concentrations were considerably raised compared to the normal range. Treatment with metoprolol caused ANF to rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was associated with a small but non-significant rise in pulmonary capillary wedge pressure. Cardiac output and systemic vascular resistance were unchanged at 24 h. In contrast, after celiprolol ANF fell to 90% of basal levels at 5 h and to 74% of basal level at 24 h (P = 0.019), associated with a small but non-significant fall in pulmonary capillary wedge pressure [-3.3 (2.7) mm Hg] and systemic vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) l/min (P = 0.04). BNF concentrations rose to 112% of baseline at 5 h (P = 0.09) after metoprolol but fell slightly, to 91% of baseline values, after celiprolol (NS). CONCLUSIONS--Metoprolol, even in very low doses (6.25 mg), produced a rise in ANF and BNF, although minimal haemodynamic changes were detected. In contrast, a vasodilating beta blocker was associated with a significant fall in ANF and BNF and a small rise in cardiac output. This study confirms both the advantages of vasodilating beta blockers

  4. Clinical Applications of Biomarkers in Atrial Fibrillation.

    PubMed

    Chang, Kay-Won; Hsu, Jonathan C; Toomu, Avinash; Fox, Sutton; Maisel, Alan S

    2017-08-16

    While biomarkers have greatly impacted the diagnosis and management of myocardial infarction and heart failure, the use of biomarkers has been slow to permeate management of atrial fibrillation. Guideline recommendations on the use of biomarkers in atrial fibrillation were virtually non-existent until the 2016 European Society of Cardiology guidelines on atrial fibrillation offered a class IIb recommendation to consider using biomarkers such as high sensitivity troponin and natriuretic peptide to further refine stroke and bleeding risk in atrial fibrillation patients. Biomarker levels have been associated with incident atrial fibrillation, post-operative atrial fibrillation, acute atrial fibrillation, diagnosis of myocardial infarction and heart failure in atrial fibrillation, and prognosis in atrial fibrillation. This review will offer an in-depth survey of current evidence on the use of biomarkers in atrial fibrillation and propose clinical algorithms to aid the internist in using biomarkers in atrial fibrillation management. Copyright © 2017. Published by Elsevier Inc.

  5. Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

    PubMed

    Kim, Sung-Ai; Son, Jungwoo; Shim, Chi-Young; Choi, Eui-Young; Ha, Jong-Won

    2017-03-27

    A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2 m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

  6. Effect of atrial natriuretic factor and 8-bromo cyclic guanosine 3':5'-monophosphate on ( sup 3 H)acetylcholine outflow from myenteric-plexus longitudinal muscle of the guinea pig

    SciTech Connect

    Matusak, O.; Kuchel, O.; Hamet, P. )

    1991-04-01

    We report that atrial natriuretic factor (ANF) inhibits electrically induced cholinergic twitches of longitudinal muscle in whole intestinal segments and myenteric-plexus longitudinal muscle (MPLM) strips from the guinea pig ileum. To elucidate the possible presynaptic mechanism of ANF's action, we studied spontaneous and stimulation-evoked radiolabeled acetylcholine (ACh) outflow from MPLM after incubation with ({sup 3}H)choline. We developed a method of mounting and treating MPLM preparations, which allowed us, at the same time, to record isometric contractions and to determine ({sup 3}H)ACh outflow upon electrical stimulation by a train of three pulses. ANF (5 x 10{sup {minus} 8}M), norepinephrine (2 x 10{sup {minus} 7}) M and 8-bromoguanosine 3':5'-cyclic monophosphate (10{sup {minus} 3} M) in nearly equieffective concentrations caused a similar inhibition of cholinergic twitches. However, ANF had no effect on ({sup 3}H)ACh outflow, whereas norepinephrine was found to suppress ({sup 3}H)ACh outflow and 8-bromoguanosine 3':5'-cGMP to enhanced ({sup 3}H)ACh outflow. ANF (5 x 10{sup {minus} 8} M) caused a 7.0-fold increase of cGMP over control values, predominantly in muscle layers, whereas Escherichia coli heat-stable toxin (12.5 U/ml) elicited a 35-fold increment of cGMP in the extramuscular layer. Thus, ANF is able to elevate cGMP in intestinal smooth muscle and to inhibit cholinergic contractions of MPLM. This inhibition is mimicked by exogenous cGMP and by endogenously generated cyclic nucleotides. We suggest that the depressive action of ANF on cholinergic contractions of MPLM is mediated via its postsynaptic impact implicating elevation of cGMP in smooth muscle.

  7. Biologic and physical characteristics of the non-peptidic, non-digitalis-like natriuretic hormone.

    PubMed

    Bricker, N S; Zea, L; Shapiro, M; Sanclemente, E; Shankel, S

    1993-11-01

    At least three independent groups of natriuretic hormones have been isolated over the past ten years. Two, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), are proteins and the third is made up of digitalis-like substances (DLS). The present report concerns the isolation, substantial purification and biologic actions of an entirely different natriuretic hormone (NH) which appears to be steroidal in nature and an isomer of cortisone. The source of NH was uremic urine. Purification involved successive chromatographic steps including gel filtration and multiple HPLC runs through C-18 resins. A translucent crystal ultimately was obtained. The product was examined using mass spectroscopy with trimethylsilyl derivatization. Only one compound was identifiable. The characteristics of the molecule include: a molecular weight, 360.4; a molecular formula, C21H28O5; a steroidal nucleus; UV absorption at 220 and 290 nm; and intrinsic fluorescence. The onset of action occurs within minutes both in the rat and, as previously shown, in several in vitro systems including the frog skin, toad bladder, fibroblasts and renal tubular epithelial cells grown in culture and isolated perfused cortical collecting tubules. In contrast to DLS, NH has been previously shown not to cross react with digoxin antibodies. Moreover, when given to intact rats, it produces a profound natriuresis but little or no kaliuresis. In contrast to ANF and BNP the compound is active orally as well as intravenously. It is clearly different from cortisone, based both on its biologic and mass spectroscopic characteristics.

  8. Cardiac melanocytes influence atrial reactive oxygen species involved with electrical and structural remodeling in mice

    PubMed Central

    Hwang, Hayoung; Liu, Fang; Petrenko, Nataliya B; Huang, Jianhe; Schillinger, Kurt J; Patel, Vickas V

    2015-01-01

    Cardiac melanocyte-like cells (CMLCs) contribute to atrial arrhythmias when missing the melanin synthesis enzyme dopachrome tautomerase (Dct). While scavenging reactive oxygen species (ROS) in Dct-null mice partially suppressed atrial arrhythmias, it remains unclear if CMLCs influence atrial ROS and structure or if the electrical response of CMLCs to ROS differs from that of atrial myocytes. This study is designed to determine if CMLCs contribute to overall atrial oxidative stress or structural remodeling, and if ROS affects the electrophysiology of CMLCs differently than atrial myocytes. Immunohistochemical analysis showed higher expression of the oxidative marker 8-hydroxy-2′-deoxyguanosine in Dct-null atria versus Dct-heterozygous (Dct-het) atria. Exposing isolated CMLCs from Dct-het and Dct-null mice to hydrogen peroxide increased superoxide anion more in Dct-null CMLCs. Trichrome staining showed increased fibrosis in Dct-null atria, and treating Dct-null mice with the ROS scavenger Tempol reduced atrial fibrosis. Action potential recordings from atrial myocytes and isolated Dct-het and Dct-null CMLCs in response to hydrogen peroxide showed that the EC50 for action potential duration (APD) prolongation of Dct-null CMLCs was 8.2 ± 1.7 μmol/L versus 16.8 ± 2.0 μmol/L for Dct-het CMLCs, 19.9 ± 2.1 μmol/L for Dct-null atrial myocytes, and 20.5 ± 1.9 μmol/L for Dct-het atrial myocytes. However, APD90 was longer in CMLCs versus atrial myocytes in response to hydrogen peroxide. Hydrogen peroxide also induced more afterdepolarizations in CMLCs compared to atrial myocytes. These studies suggest that Dct within CMLCs contributes to atrial ROS balance and remodeling. ROS prolongs APD to a greater extent and induces afterdepolarizations more frequently in CMLCs than in atrial myocytes. PMID:26400986

  9. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

    PubMed Central

    Dietrich, Johannes W.; Müller, Patrick; Schiedat, Fabian; Schlömicher, Markus; Strauch, Justus; Chatzitomaris, Apostolos; Klein, Harald H.; Mügge, Andreas; Köhrle, Josef; Rijntjes, Eddy; Lehmphul, Ina

    2015-01-01

    Background Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms. PMID:26279999

  10. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling.

    PubMed

    Dietrich, Johannes W; Müller, Patrick; Schiedat, Fabian; Schlömicher, Markus; Strauch, Justus; Chatzitomaris, Apostolos; Klein, Harald H; Mügge, Andreas; Köhrle, Josef; Rijntjes, Eddy; Lehmphul, Ina

    2015-06-01

    Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms.

  11. Novel bifunctional natriuretic peptides as potential therapeutics.

    PubMed

    Dickey, Deborah M; Burnett, John C; Potter, Lincoln R

    2008-12-12

    Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the promiscuous nature of CNP in this species. Interesting, the DNP tail alone had no effect on any NPR even though it is effective in vivo. To further increase the potency of CD-NP for NPR-A, we converted two different triplet sequences within the CNP ring to their corresponding residues in BNP. Both variants demonstrated increased affinity and full agonist activity for NPR-A, whereas one was as potent as any NPR-A activator known. In contrast to a previous report, we found that DNP binds the natriuretic peptide clearance receptor (NPR-C). However, none of the chimeric peptides bound NPR-C with significantly higher affinity than endogenous ligands. We suggest that bifunctional chimeric peptides represent a new generation of natriuretic peptide therapeutics.

  12. Involvement of a novel GATA4 mutation in atrial septal defects.

    PubMed

    Liu, Xing-Yuan; Wang, Juan; Zheng, Jing-Hao; Bai, Kai; Liu, Zhong-Min; Wang, Xiao-Zhou; Liu, Xu; Fang, Wei-Yi; Yang, Yi-Qing

    2011-07-01

    Atrial septal defect (ASD) is one of the most common types of congenital heart disease and is associated with a significant increase in the morbidity and mortality of affected individuals. Accumulating evidence indicates that genetic defects play important roles in the pathogenesis of congenital ASD. However, ASD is genetically heterogeneous and the genetic determinants for ASD in the majority of the patients remain to be identified. In this study, the entire coding region of GATA4, a gene encoding a zinc-finger transcription factor crucial to embryogenesis, was initially sequenced in 120 unrelated patients with ASD. The available relatives of patients carrying the identified mutation and 200 ethnicity-matched unrelated control individuals were genotyped. The functional characteristics of the GATA4 mutant were compared to its wild-type counterpart using a luciferase reporter assay system. A novel heterozygous missense GATA4 mutation, p.G21V, was identified in 2 unrelated families with ASD, which was not detected in the control population nor reported in the human gene mutation database. Alignment of multiple GATA4 proteins displayed that the affected amino acid residue was highly conserved across species. Functional analysis showed that the p.G21V GATA4 mutation was associated with a decreased transcriptional activity. The findings underscore the pathogenic link between compromised GATA4 function and congenital ASD, providing new insight into the molecular mechanism involved in this common form of congenital cardiovascular anomalies.

  13. Isolated Atrial Amyloidosis in Patients with Various Types of Atrial Fibrillation.

    PubMed

    Sukhacheva, T V; Eremeeva, M V; Ibragimova, A G; Vaskovskii, V A; Serov, R A; Revishvili, A Sh

    2016-04-01

    The myocardium of the right and left atrial appendages (auricles) in patients with paroxysmal, persistent, and permanent forms of atrial fibrillation was examined by histological methods and electron microscopy. Isolated atrial amyloidosis was detected in the left (50.0-56.3% patients) and in the right (45.0-55.6% patients) atrial appendages. In all cases, immunohistochemistry revealed atrial natriuretic peptide in fibrillary amyloid deposits. Ultrastructurally, amyloid masses formed clusters of myofibrils 8-10 nm in diameter. They were chaotically located in the extracellular space along the sarcolemma as well as in membrane invaginations, dilated tubules of cardiomyocyte T-tubular system, and vascular walls. Amyloidosis was predominantly observed in women; its degree positively correlated with age of patients and duration of atrial fibrillation but negatively correlated with atrial fibrosis. The study revealed positive (in permanent atrial fibrillation) and negative (in paroxysmal atrial fibrillation) correlation of amyloidosis with myofibril content in atrial cardiomyocytes.

  14. Plasma immunoreactive atrial natriuretic factor (IR-ANF) increases markedly after alpha 2-adrenergic stimulation with clonidine in normally-hydrated rats.

    PubMed

    Baranowska, B; Gutkowska, J; Cantin, M; Genest, J

    1987-02-27

    Clonidine, an alpha 2-adrenergic agonist, induced a marked, dose-related increase of plasma IR-ANF in normally-hydrated rats. Maximal ANF release was observed at 10 min after injection of 50 micrograms clonidine, rising from 40.5 +/- 4.6 pg/ml (X +/- SEM) to 1064.4 +/- 22.4 pg/ml. This effect on plasma IR-ANF was partially blocked by pretreatment with 0.8 mg naloxone, whereas synthetic Arg8-vasopressin (AVP) did not inhibit clonidine's action. These findings indicate that increased ANF release may be involved in the mechanism of clonidine-induced diuresis. The clonidine's effect on ANF release may be mediated via activation of opioid receptors besides stimulation of alpha 2-adrenergic receptors.

  15. Chloride Channels are Involved in the Development of Atrial Fibrillation - A Transcriptomic and proteomic Study.

    PubMed

    Jiang, Yi-Yao; Hou, Hai-Tao; Yang, Qin; Liu, Xiao-Cheng; He, Guo-Wei

    2017-08-31

    Electrical and structural remodeling processes are contributors to the self-perpetuating nature of atrial fibrillation (AF). However, their correlation has not been clarified. In this study, human atrial tissues from the patients with rheumatic mitral valve disease in either sinus rhythm or persistent AF were analyzed using a combined transcriptomic and proteomic approach. An up-regulation in chloride intracellular channel (CLIC) 1, 4, 5 and a rise in type IV collagen were revealed. Combined with the results from immunohistochemistry and electron microscope analysis, the distribution of type IV collagen and effects of fibrosis on myocyte membrane indicated the possible interaction between CLIC and type IV collagen, confirmed by protein structure prediction and co-immunoprecipitation. These results indicate that CLICs play an important role in the development of atrial fibrillation and that CLICs and structural type IV collagen may interact on each other to promote the development of AF in rheumatic mitral valve disease.

  16. Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation.

    PubMed

    Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

    2017-03-08

    Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (IKv1.5) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (IhERG). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (IKir2.1). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of IKv1.5 and IhERG, which contributed to preventing the development and duration of AF.

  17. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein

    PubMed Central

    Alqahtani, Mashael F.; Smith, Craig M.; Weiss, Scott L.; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S.

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004–0.174, 13), day 2 (0.020, 0.002–0.109, 10), and day 3 (0.018, 0.003–0.058, 23) compared with febrile (0.705, 0.187–1.778, 22) and healthy (0.7, 0.4–1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2–54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3–20.6, 11). MMP-9/TIMP-1 ratios

  18. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

    PubMed

    Alqahtani, Mashael F; Smith, Craig M; Weiss, Scott L; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were

  19. Atrial natriuretic factor in human plasma

    SciTech Connect

    Gutkowska, J.; Bonan, R.; Roy, D.; Bourassa, M.; Garcia, R.; Thibault, G.; Genest, J.; Cantin, M.

    1986-08-29

    A reproducible and sensitive radioimmunoassay (RIA) was developed to measure ANF in human plasma. Immunoreactive ANF was extracted from plasma with Sep-Pak cartridges, using 0.2% ammonium acetate (pH 4) with acetonitrile. The sensitivity of the assay was 3.9 pg/ml. The coefficient of variance for inter-assay and intra-assay was 16.8% and 6.8%, respectively. In normal healthy subjects (n = 67), ANF content was 11.9 +/- 1.3 pg/ml (mean +/- SEM). Significantly-higher ANF concentrations were found in proximal coronary sinus blood, being 6 to 37 times greater than in the peripheral circulation. Comparison of the prior extraction method with direct RIA revealed a good correlation (r = 91) in samples containing higher than 100 pg/ml ANF. No correlation was observed with lower values. The elution profiles of reverse-phase HPLC of peripheral and coronary sinus plasma extracts were similar but somewhat complex, with the main immunoreactive peak corresponding to a low-molecular-weight peptide.

  20. Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide.

    PubMed

    Centeno, José M; Marrachelli, Vannina G; Miranda, Luis; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

    2013-02-15

    The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabetic than in control rabbits. Endothelium removal did not modify the relaxation to BNP in control rabbits but increased this relaxation in diabetic rabbits. In control rabbits, indomethacin inhibited the BNP-induced relaxation in the presence and in the absence of endothelium. In diabetic rabbits, indomethacin did not modify the BNP-induced relaxation in arteries with endothelium and inhibited it in arteries without endothelium. In the presence of BNP the carotid artery released thromboxane A2 and prostacyclin, and the release of endothelial prostacyclin was inhibited in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to BNP, and these inhibitions were lower in diabetic than in control rabbits. In conclusion, our results provide a new understanding concerning the mechanisms of the diabetes-induced hyporeactivity of the carotid artery to BNP, that at least include the loss of endothelial prostacyclin and a reduced participation of ATP-sensitive K(+) channels (KATP) and voltage-sensitive K(+) channels (KV). Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Vascular Tone Regulation Induced by C-Type Natriuretic Peptide: Differences in Endothelium-Dependent and -Independent Mechanisms Involved in Normotensive and Spontaneously Hypertensive Rats

    PubMed Central

    Caniffi, Carolina; Cerniello, Flavia M.; Gobetto, María N.; Sueiro, María L.; Arranz, Cristina

    2016-01-01

    Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one in both groups. In contrast, blockade of cyclooxygenase or subtype 2 bradykinin receptor increased CNP potency only in SHR. In both Wistar and SHR, CNP relaxation was blunted by tetraethylammonium and partially inhibited by BaCl2 and iberiotoxin, indicating that it was due to opening of the Kir and BKCa channels. However, SHR seem to be more sensitive to Kir channel blockade and less sensitive to BKCa channel blockade than normotensive rats. In addition, CNP decreases HVR in Wistar and SHR, but the effect of CNP increasing blood flow was more marked in SHR. We conclude that CNP induces aorta relaxation by activation of the nitric oxide system and opening of potassium channels, but the response to the peptide is impaired in conductance vessel of hypertensive rats. PMID:27936197

  2. Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice.

    PubMed

    Nakagawa, M; Tanaka, I; Mukoyama, M; Suga, S; Ogawa, Y; Tamura, N; Ishibashi, R; Goto, M; Nakagawa, O; Sugawara, A; Nakao, K

    2001-03-01

    Brain natriuretic peptide (BNP) is a ventricular hormone with natriuretic, diuretic and vasodilatory actions. Acute infusion of BNP reduces cardiac pre- and after-load in healthy and diseased subjects, but its long-term therapeutic usefulness remains unclear. We prepared a monoclonal antibody specific to mouse BNP, and characterized transgenic mice overexpressing BNP in the liver (BNP-Tg mice) as a model of its chronic overproduction. Radioimmunoassay and neutralization experiments using the monoclonal antibody, KY-mBNP-I, were performed in BNP-Tg mice in conjunction with examinations of blood pressure (BP) and other markers for body fluid homeostasis. We developed highly sensitive radioimmunoassay to mouse BNP. In BNP-Tg mice, the plasma BNP concentration increased more than 100-fold, while ventricular BNP concentration did not alter, suggesting that ventricular BNP production was not down-regulated in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than nontransgenic (nonTg) littermates, accompanied with marked reduction in the atrial natriuretic peptide (ANP) concentration, that may be due to binding of circulating BNP to the natriuretic peptide receptors. BNP-Tg mice showed significantly low arterial BP, and a bolus intraperitoneal administration of KYmBNP-I completely abolished enhanced cGMP excretion in the urine and significantly increased the systolic BP. These results suggested that biological actions of BNP last and reduce cardiac overload in its longterm overproduction in the transgenic mouse model.

  3. Management of atrial fibrillation.

    PubMed

    Moukabary, Talal; Gonzalez, Mario D

    2015-07-01

    Atrial fibrillation is a very common clinical problem with a high prevalence that is expected to rise over time because of increasing risk factors (eg, age, obesity, hypertension). This high prevalence is also associated with high cost, because atrial fibrillation represents about 1% of overall health care spending. The management of atrial fibrillation involves multiple facets: (1) management of underlying disease if present and the management of atrial fibrillation risk factors, (2) prevention of thromboembolism, (3) control of the ventricular rate during atrial fibrillation, and (4) restoration and maintenance of normal sinus rhythm.

  4. Patients' experiences of communication and involvement in decision-making about atrial fibrillation treatment in consultations with nurses and physicians.

    PubMed

    Siouta, Eleni; Hellström Muhli, Ulla; Hedberg, Berith; Broström, Anders; Fossum, Bjöörn; Karlgren, Klas

    2016-09-01

    Insights in consultations across patient interactions with physicians and nurses are of vital importance for strengthening the patients' involvement in the treatment decision-making process. The experience of involvement and communication in decision-making from the patients' perspective has been sparsely explored. To examine how patients describe involvement in and communication about decision-making regarding treatment in consultations with nurses and physicians. Twenty-two patients with atrial fibrillation (AF), aged 37-90 years, were interviewed directly after their consultations with nurses and physicians in outpatient AF clinics in six Swedish hospitals. In consultations with nurses, the patients felt involved when obtaining clarifications about AF as a disease and its treatment and when preparing for and building up confidence in decision-making. In consultations with physicians, the patients felt involved when they could cooperate in decision-making, when acquiring knowledge, and when they felt that they were being understood. One shared category was found in consultations with both nurses and physicians, and the patients felt involved when they had a sense of trust and felt secure during and between consultations. Patients with AF stated that they would need to acquire knowledge and build up confidence and ability in order to be effectively involved in the decision-making about treatment. Despite not being actively involved in decision-making, patients felt involved through experiencing supportive and confirming communication. Attention must be given to the relationship with the patient to create the conditions for patient involvement in the consultation. This can be achieved through supportive communication attempting to create a feeling of clarity and building confidence. This will support involvement in decision-making concerning AF treatment and feelings of being understood and of trust in physicians and/or nurses. © 2015 Nordic College of Caring

  5. Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

    PubMed

    Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

    2017-08-26

    Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT2R2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support,education, and patient-involvement

  6. Natriuretic peptides buffer renin-dependent hypertension.

    PubMed

    Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

    2014-06-15

    The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

  7. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    PubMed

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. Copyright © 2016 the American Physiological Society.

  8. New aspects of the interactions between the cardiovascular nitric oxide system and natriuretic peptides.

    PubMed

    Costa, María A; Arranz, Cristina T

    2011-03-11

    Arterial blood pressure is regulated by a variety of endocrine, autocrine and neuronal systems. Natriuretic peptides and nitric oxide are important factors that exert synergistic vascular and cardiac actions and their activities are closely linked. The existence of a novel signal transduction mechanism involved in activation of nitric oxide synthase via natriuretic peptides is currently being explored. Since several cardiovascular disorders are associated with dysfunction of natriuretic peptides activity, selective modulation of the natriuretic peptides pathway represents an important therapeutic target. This review article highlights the current findings on cross-talk between natriuretic peptides and the nitric oxide system. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Acute Metabolic Influences on the Natriuretic Peptide System in Humans

    PubMed Central

    Hamid, Tariq; Arora, Garima; Agha, Obiajulu; Allen, Kaitlin; Tainsh, Robert E.T.; Hu, Dongjian; Ryan, Romy A.; Domian, Ibrahim J.; Buys, Emmanuel S.; Bloch, Donald B.; Prabhu, Sumanth D.; Bloch, Kenneth D.; Newton-Cheh, Christopher; Wang, Thomas J.

    2016-01-01

    BACKGROUND The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress. OBJECTIVES This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms. METHODS Normotensive subjects (N = 33) were given a high-carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell–derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-κB) in the glucose-mediated effects was investigated using a NF-κB inhibitor and expression plasmids encoding NF-κB subunits. RESULTS We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-κB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-κB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells. CONCLUSIONS Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-κB signaling. PMID:26892417

  10. Effect of chronic treatment with deoxycorticosterone acetate on content of a natriuretic substance in atria of rats.

    PubMed

    Hathaway, S J; Fregly, M J; Wilson, K M; Papanek, P E; Henley, W N

    1986-10-01

    Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.

  11. Dwarfism and early death in mice lacking C-type natriuretic peptide

    PubMed Central

    Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

    2001-01-01

    Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

  12. Dwarfism and early death in mice lacking C-type natriuretic peptide.

    PubMed

    Chusho, H; Tamura, N; Ogawa, Y; Yasoda, A; Suda, M; Miyazawa, T; Nakamura, K; Nakao, K; Kurihara, T; Komatsu, Y; Itoh, H; Tanaka, K; Saito, Y; Katsuki, M; Nakao, K

    2001-03-27

    Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc(-/-) mice). The Nppc(-/-) mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc(-/-) mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia.

  13. B and C types natriuretic peptides modulate norepinephrine uptake and release in the rat hypothalamus.

    PubMed

    Vatta, M S; Presas, M; Bianciotti, L G; Zarrabeitia, V; Fernández, B E

    1996-09-16

    We previously reported that atrial natriuretic factor (ANF) regulates catecholamine metabolism in the central nervous system. ANF, B and C types natriuretic peptides (BNP and CNP) also play a regulatory role in body fluid homeostasis, cardiovascular activity and hormonal and neuro-hormonal secretions. The aim of the present work was to investigate BNP and CNP effects on the uptake and release of norepinephrine (NE) in rat hypothalamic slices incubated in vitro. Results showed that BNP (100 nM) and CNP (1, 10 and 100 nM) enhanced total and neuronal [3H]NE uptake but did not modify non-neuronal uptake. BNP (100 nM) and CNP (1 nM) caused a rapid increase in NE uptake (1 min), which was sustained for 60 min. BNP (100 nM) did not modify the intracellular distribution of NE; however, 1 nM CNP increased the granular store and decreased the cytosolic pool of NE. BNP (100 nM) and CNP (1, 10 and 100 nM), diminished spontaneous NE release. In addition, BNP (1, 10, 100 nM) and CNP (1, 10 and 100 pM, as well as 1, 10 and 100 nM) reduced NE output induced by 25 mM KCl. These results suggest that BNP and CNP may be involved in the regulation of several central as well as peripheral physiological functions through the modulation of noradrenergic neurotransmission at the presynaptic neuronal level. Present results provide evidence to consider CNP as the brain natriuretic peptide since physiological concentrations of this peptide (pM) diminished NE evoked release.

  14. B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.

    PubMed

    Torres-Courchoud, I; Chen, H H

    2016-10-01

    Natriuretic peptides are a family of peptides with similar structures, but are genetically distinct with diverse actions in cardiovascular, renal and fluid homeostasis. The family consists of an atrial natriuretic peptide (ANP) and a brain natriuretic peptide (BNP) of myocardial cell origin, a C-type natriuretic peptide (CNP) of endothelial origin, and a urodilatin (Uro) which is processed from a prohormone ANP in the kidney. Nesiritide, a human recombinant BNP, was approved by the Federal Drug Administration (FDA) for the management of acute heart failure (AHF) in 2001. Human recombinant ANP (Carperitide) was approved for the same clinical indication in Japan in 1995, and human recombinant Urodilatin (Ularitide) is currently undergoing phase III clinical trial (TRUE AHF). This review will provide an update on important issues regarding the role of BNP in fluid hemostasis as a biomarker and therapeutics in AHF.

  15. Natriuretic peptide family as a novel antimigration factor of vascular smooth muscle cells.

    PubMed

    Ikeda, M; Kohno, M; Yasunari, K; Yokokawa, K; Horio, T; Ueda, M; Morisaki, N; Yoshikawa, J

    1997-04-01

    Vascular smooth muscle cell (SMC) migration is proposed to be an important process in the initiation and/or progression of atherosclerosis. The present study examined the effects of the natriuretic peptide family (atrial, brain, and C-type natriuretic peptides; ANP, BNP, and CNP) on the migration of cultured rat SMCs, using Boyden's chamber methods. Fetal calf serum (FCS) and platelet-derived growth factor (PDGF)-BB potently stimulated SMC migration. Rat ANP(1-28), rat BNP-45, and rat CNP-22 clearly inhibited SMC migration stimulated with FCS or PDGF-BB in a concentration-dependent manner. CNP-22 had the most potent inhibitory effect compared with other natriuretic peptides. When PDGF-BB-induced migration was separated into chemotactic and chemokinetic activities, the chemotactic component was strongly inhibited by these natriuretic peptides. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cyclic GMP. The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, and an activator of the cytosolic guanylate cyclase, sodium nitroprusside, significantly inhibited FCS- and PDGF-BB-stimulated migration in a concentration-dependent manner. These results suggest that natriuretic peptides, especially CNP-22, inhibit FCS- or PDGF-BB-stimulated SMC migration at least in part through a cyclic GMP-dependent process. Thus, the natriuretic peptide family may play a role as an antimigration factor of SMCs under certain circumstances.

  16. Genetic variation in the natriuretic peptide system and heart failure.

    PubMed

    Lanfear, David E

    2010-05-01

    Heart failure (HF) is a modern epidemic and is one of the few cardiovascular diseases which is increasing in prevalence. The growing importance of the Natriuretic Peptide (NP) system in HF is well recognized. Laboratory tests for B-type Natriuretic Peptide (BNP) have proven value as diagnostic and prognostic tools in HF and are now part of routine clinical care. Furthermore, recombinant atrial natriuretic peptide (ANP) (carperitide) and BNP (nesiritide) and are approved HF therapies in Japan and the US, respectively and additional natriuretic peptides (e.g., CNP, urodilatin, and designer NPs) are under investigation for use in HF. Common genetic sequence variants are increasingly being recognized as determinants of disease risk or drug response and may help explain a portion of the inter-individual variation in the human NP system. This review describes current knowledge of NP system genetic variation as it pertains to HF as well as ongoing studies and where the field is expected to progress in the near future. To briefly summarize, NP system genetic variants have been associated with alterations in gene expression, NP levels, and cardiovascular disease. The next step forward will include specific investigations into how this genetic variation can advance 'Personalized Medicine', such as whether they impact the utility of diagnostic BNP testing or effectiveness of therapeutic NP infusion. This is already in progress, with pharmacogenetic studies of nesiritide currently underway. We expect that within 5 years there should be a reasonable idea of whether NP system genetic variation will have important clinical implications.

  17. Primary neural involvement in renal haemodynamic and functional responses to prolonged stimulation of atrial receptors in anaesthetized dogs.

    PubMed

    Majid, D S; Karim, F

    1995-07-01

    To determine the precise contributory role of neural and humoral factors in the efferent mechanism of the atrial receptor-renal reflex, we have examined the effects of prolonged (45 min) stimulation of left atrial receptors on renal haemodynamics and function simultaneously in both kidneys (right kidney intact and left kidney denervated) of anaesthetized dogs. Aortic pressure in these dogs was held constant by means of an arterial reservoir connected to the aorta; heart rate changes were prevented by blocking beta 1-adrenoceptor activity with atenolol (2 mg kg-1 i.v.). Localized stimulation of atrial receptors in six dogs increased renal blood flow (6 +/- 2%), creatinine clearance (11 +/- 4%), urine flow (9 +/- 3%), sodium excretion (14 +/- 7%) and osmolal excretion (10 +/- 4%), and decreased free water clearance (14 +/- 7%) in intact kidneys, but led to no changes in denervated kidneys. In an additional four dogs, cooling the vagus nerves to 6-7 degrees C or cutting them in the neck abolished the renal responses to stimulation of atrial receptors in these stabilized preparations. These data clearly demonstrate that the renal responses to prolonged stimulation of atrial receptors are primarily mediated via myelinated vagal afferents and renal sympathetic efferents.

  18. Betaxolol improves the survival rate and changes natriuretic peptide expression in rats with heart failure.

    PubMed

    Watanabe, Kenichi; Juan, Wen; Narasimman, Gurusamy; Ma, Meilei; Inoue, Mikio; Saito, Yuki; Wahed, Mir I I; Nakazawa, Mikio; Hasegawa, Go; Naito, Makoto; Tachikawa, Hitoshi; Tanabe, Naohito; Kodama, Makoto; Aizawa, Yoshifusa; Yamamoto, Tadashi; Yamaguchi, Kenichi; Takahashi, Toshihiro

    2003-01-01

    The cardioprotective effects of betaxolol were studied in a rat model with heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups; 0.1 mg/kg betaxolol per day (group 0.1), 1.0 mg/kg betaxolol per day (group 1), 10 mg/kg betaxolol per day (group 10), and vehicle (0.5% methylcellulose, group V) (all groups, n = 13). After oral administration for 1 month, the heart weight, the mRNA expression of atrial natriuretic peptide and brain natriuretic peptide in the left ventricle, the plasma atrial natriuretic peptide concentration, the mean blood pressure, the heart rate, the central venous pressure, the peak left ventricular pressure, the left ventricular end-diastolic pressure and its first derivative +/-dP/dt, and the area of myocardial fibrosis were measured. Betaxolol reduced the heart rate, the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA expression and the atrial natriuretic peptide concentration [group N (normal rats), 367 +/- 4 beats/min, 100%, 100% and 78 +/- 7 pg/ml, respectively; group V, 391 +/- 9 beats/min, 761 +/- 68% versus group N, 317 +/- 42% versus group N and 4374 +/- 312 pg/ml, respectively; group 0.1, 387 +/- 10 beats/min, 621 +/- 78%, 288 +/- 41% and 2875 +/- 331 pg/ml, respectively; group 1, 323 +/- 9 beats/min, 442 +/- 84%, 148 +/- 12% and 884 +/- 51 pg/ml, respectively; and group 10, 312 +/- 8 beats/min, 97 +/- 18%, 92 + 9% and 453 +/- 53 pg/ml, respectively], and increased survival (group V, 62%; group 0.1, 69%; groups N, 1 and 10, 100%). Betaxolol did not significantly alter the heart weight, the hemodynamic parameters or the area of fibrosis. These observations suggest that betaxolol may improve the survival rate by reducing sudden death and changing the atrial natriuretic peptide and brain natriuretic peptide mRNA expression in patients with heart failure.

  19. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation

    PubMed Central

    Zhang, Ke K.; Xiang, Menglan; Zhou, Lun; Liu, Jielin; Curry, Nathan; Heine Suñer, Damian; Garcia-Pavia, Pablo; Zhang, Xiaohua; Wang, Qin; Xie, Linglin

    2016-01-01

    Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5+/−, Osr1+/−, Osr1−/− and Tbx5+/−/Osr1+/− mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene–gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny. PMID:26744331

  20. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation.

    PubMed

    Zhang, Ke K; Xiang, Menglan; Zhou, Lun; Liu, Jielin; Curry, Nathan; Heine Suñer, Damian; Garcia-Pavia, Pablo; Zhang, Xiaohua; Wang, Qin; Xie, Linglin

    2016-03-15

    Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5(+/) (-), Osr1(+/-), Osr1(-/-) and Tbx5(+/-)/Osr1(+/-) mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene-gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny.

  1. Intrinsic defence capacity and therapeutic potential of natriuretic peptides in pulmonary hypertension associated with lung fibrosis

    PubMed Central

    Baliga, R S; Scotton, C J; Trinder, S L; Chambers, R C; MacAllister, R J; Hobbs, A J

    2014-01-01

    BACKGROUND AND PURPOSE Idiopathic pulmonary fibrosis (IPF) is a progressive fibro-proliferative disorder refractory to current therapy commonly complicated by the development of pulmonary hypertension (PH); the associated morbidity and mortality are substantial. Natriuretic peptides possess vasodilator and anti-fibrotic actions, and pharmacological augmentation of their bioactivity ameliorates renal and myocardial fibrosis. Here, we investigated whether natriuretic peptides possess an intrinsic cytoprotective function preventing the development of pulmonary fibrosis and associated PH, and whether therapeutics targeting natriuretic peptide signalling demonstrate efficacy in this life-threatening disorder. EXPERIMENTAL APPROACH Pulmonary haemodynamics, right ventricular function and markers of lung fibrosis were determined in wild-type (WT) and natriuretic peptide receptor (NPR)-A knockout (KO) mice exposed to bleomycin (1 mg·kg−1). Human myofibroblast differentiation was studied in vitro. KEY RESULTS Exacerbated cardiac, vascular and fibrotic pathology was observed in NPR-A KO animals, compared with WT mice, exposed to bleomycin. Treatment with a drug combination that raised circulating natriuretic peptide levels (ecadotril) and potentiated natriuretic peptide-dependent signalling (sildenafil) reduced indices of disease progression, whether administered prophylactically or to animals with established lung disease. This positive pharmacodynamic effect was diminished in NPR-A KO mice. Atrial natriuretic peptide and sildenafil synergistically reduced TGFβ-induced human myofibroblast differentiation, a key driver of remodelling in IPF patients. CONCLUSIONS AND IMPLICATIONS These data highlight an endogenous host-defence capacity of natriuretic peptides in lung fibrosis and PH. A combination of ecadotril and sildenafil reversed the pulmonary haemodynamic aberrations and remodelling that characterize the disease, advocating therapeutic manipulation of natriuretic

  2. [Atrial fibrillation].

    PubMed

    Cárdenas, Manuel

    2007-01-01

    Atrial fibrillation is an arrhythmia characterized by no-coordinated atrial contraction that results in an inefficient atrial systole. The clinical classification of atrial fibrillation includes: ocassional, paroxysmal, persistent, and permanent. Multiple mechanisms have been described and accounts for a single ECG manifestation. Treatment should be individualized and has to considered several aspects including age, associated heart disease, and symptoms. Treatment strategies are: rhythm control, rate control, and thromboprophylaxis.

  3. The MAPK pathway is involved in the regulation of rapid pacing-induced ionic channel remodeling in rat atrial myocytes.

    PubMed

    Cheng, Wei; Zhu, Yun; Wang, Haidong

    2016-03-01

    Alterations to the expression L‑type calcium channels (LTCCs) and Kv4.3 potassium channels form the possible basis of atrial electrical remodeling during rapid pacing. The mitogen‑activated protein kinase (MAPK) pathway is affected by increases in cytoplasmic Ca2+, and therefore represents an attractive candidate for the regulation and mediation of Ca2+‑induced ion channel remodeling. The present study aimed to investigate alterations to the ion channel‑MAPK axis, and to determine its influence on ion channel remodeling during atrial fibrillation. Rat atrial myocytes were isolated, cultured, and in vitro rapid pacing was established. Intracellular Ca2+ signals were monitored using the Fluo‑3/AM Ca2+ indicator. Verapamil, PD98058 and SB203580 were added to the culture medium of various groups at specific time‑points. The mRNA expression levels of LTCC‑α1c and Kv4.3 potassium channels were detected by reverse transcription‑polymerase chain reaction. Western blotting was performed to determine the expression levels of channel and signaling proteins. The results demonstrated that fast pacing significantly increased the intracellular Ca2+ concentration in atrial myocytes, whereas treatment with verapamil markedly inhibited this increase. In addition, verapamil significantly antagonized the rapid pacing‑induced activation of extracellular signal‑regulated kinase (ERK) and p38MAPK. These results indicated that the MAPK pathway may have an important role in the opening of LTCCs, and alterations to MAPK molecule expression could affect the expression and remodeling of ion channels.

  4. [Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

    PubMed

    Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

    2013-01-01

    Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure.

  5. The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in mice

    PubMed Central

    Kuhn, Michaela; Völker, Katharina; Schwarz, Kristine; Carbajo-Lozoya, Javier; Flögel, Ulrich; Jacoby, Christoph; Stypmann, Jörg; van Eickels, Martin; Gambaryan, Stepan; Hartmann, Michael; Werner, Matthias; Wieland, Thomas; Schrader, Jürgen; Baba, Hideo A.

    2009-01-01

    Cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) modulate blood pressure and volume by activation of the receptor guanylyl cyclase–A (GC-A) and subsequent intracellular cGMP formation. Here we report what we believe to be a novel function of these peptides as paracrine regulators of vascular regeneration. In mice with systemic deletion of the GC-A gene, vascular regeneration in response to critical hind limb ischemia was severely impaired. Similar attenuation of ischemic angiogenesis was observed in mice with conditional, endothelial cell–restricted GC-A deletion (here termed EC GC-A KO mice). In contrast, smooth muscle cell–restricted GC-A ablation did not affect ischemic neovascularization. Immunohistochemistry and RT-PCR revealed BNP expression in activated satellite cells within the ischemic muscle, suggesting that local BNP elicits protective endothelial effects. Since within the heart, BNP is mainly induced in cardiomyocytes by mechanical load, we investigated whether the natriuretic peptide/GC-A system also regulates angiogenesis accompanying load-induced cardiac hypertrophy. EC GC-A KO hearts showed diminished angiogenesis, mild fibrosis, and diastolic dysfunction. In vitro BNP/GC-A stimulated proliferation and migration of cultured microvascular endothelia by activating cGMP-dependent protein kinase I and phosphorylating vasodilator-stimulated phosphoprotein and p38 MAPK. We therefore conclude that BNP, produced by activated satellite cells within ischemic skeletal muscle or by cardiomyocytes in response to pressure load, regulates the regeneration of neighboring endothelia via GC-A. This paracrine communication might be critically involved in coordinating muscle regeneration/hypertrophy and angiogenesis. PMID:19487812

  6. Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes phosphoinositide hydrolysis, Ca2+ release, and activation of protein kinase C

    PubMed Central

    Pandey, Kailash N.

    2014-01-01

    Thus far, three related natriuretic peptides (NPs) and three distinct sub-types of cognate NP receptors have been identified and characterized based on the specific ligand binding affinities, guanylyl cyclase activity, and generation of intracellular cGMP. Atrial and brain natriuretic peptides (ANP and BNP) specifically bind and activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), and C-type natriuretic peptide (CNP) shows specificity to activate guanylyl cyclase/natriuretic peptide receptor-B (GC-B/NPRB). All three NPs bind to natriuretic peptide receptor-C (NPRC), which is also known as clearance or silent receptor. The NPRA is considered the principal biologically active receptor of NP family; however, the molecular signaling mechanisms of NP receptors are not well understood. The activation of NPRA and NPRB produces the intracellular second messenger cGMP, which serves as the major signaling molecule of all three NPs. The activation of NPRB in response to CNP also produces the intracellular cGMP; however, at lower magnitude than that of NPRA, which is activated by ANP and BNP. In addition to enhanced accumulation of intracellular cGMP in response to all three NPs, the levels of cAMP, Ca2+ and inositol triphosphate (IP3) have also been reported to be altered in different cells and tissue types. Interestingly, ANP has been found to lower the concentrations of cAMP, Ca2+, and IP3; however, NPRC has been proposed to increase the levels of these metabolic signaling molecules. The mechanistic studies of decreased and/or increased levels of cAMP, Ca2+, and IP3 in response to NPs and their receptors have not yet been clearly established. This review focuses on the signaling mechanisms of ANP/NPRA and their biological effects involving an increased level of intracellular accumulation of cGMP and a decreased level of cAMP, Ca2+, and IP3 in different cells and tissue systems. PMID:25202235

  7. Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes phosphoinositide hydrolysis, Ca(2+) release, and activation of protein kinase C.

    PubMed

    Pandey, Kailash N

    2014-01-01

    Thus far, three related natriuretic peptides (NPs) and three distinct sub-types of cognate NP receptors have been identified and characterized based on the specific ligand binding affinities, guanylyl cyclase activity, and generation of intracellular cGMP. Atrial and brain natriuretic peptides (ANP and BNP) specifically bind and activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), and C-type natriuretic peptide (CNP) shows specificity to activate guanylyl cyclase/natriuretic peptide receptor-B (GC-B/NPRB). All three NPs bind to natriuretic peptide receptor-C (NPRC), which is also known as clearance or silent receptor. The NPRA is considered the principal biologically active receptor of NP family; however, the molecular signaling mechanisms of NP receptors are not well understood. The activation of NPRA and NPRB produces the intracellular second messenger cGMP, which serves as the major signaling molecule of all three NPs. The activation of NPRB in response to CNP also produces the intracellular cGMP; however, at lower magnitude than that of NPRA, which is activated by ANP and BNP. In addition to enhanced accumulation of intracellular cGMP in response to all three NPs, the levels of cAMP, Ca(2+) and inositol triphosphate (IP3) have also been reported to be altered in different cells and tissue types. Interestingly, ANP has been found to lower the concentrations of cAMP, Ca(2+), and IP3; however, NPRC has been proposed to increase the levels of these metabolic signaling molecules. The mechanistic studies of decreased and/or increased levels of cAMP, Ca(2+), and IP3 in response to NPs and their receptors have not yet been clearly established. This review focuses on the signaling mechanisms of ANP/NPRA and their biological effects involving an increased level of intracellular accumulation of cGMP and a decreased level of cAMP, Ca(2+), and IP3 in different cells and tissue systems.

  8. Triiodothyronine and Brain Natriuretic Peptide

    PubMed Central

    Kozdag, Guliz; Ertas, Gokhan; Kilic, Teoman; Acar, Eser; Sahin, Tayfun; Ural, Dilek

    2010-01-01

    Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients. A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event. During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were <2.12 pg/mL for free triiodothyronine and >686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine <2.12 pg/mL and among patients with brain natriuretic peptide >686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide. In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure. PMID:20978564

  9. Resistance to endotoxic shock in mice lacking natriuretic peptide receptor-A.

    PubMed

    Panayiotou, Catherine M; Baliga, Reshma; Stidwill, Raymond; Taylor, Valerie; Singer, Mervyn; Hobbs, Adrian J

    2010-08-01

    Excessive production of nitric oxide (NO) by inducible NO synthase (iNOS) is thought to underlie the vascular dysfunction, systemic hypotension and organ failure that characterize endotoxic shock. Plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are raised in animal models and humans with endotoxic shock and correlate with the associated cardiovascular dysfunction. Since both NO and natriuretic peptides play important roles in cardiovascular homeostasis via activation of guanylate cyclase-linked receptors, we used mice lacking natriuretic peptide receptor (NPR)-A (NPR1) to establish if natriuretic peptides contribute to the cardiovascular dysfunction present in endotoxic shock. Wild-type (WT) and NPR-A knockout (KO) mice were exposed to lipopolysaccharide (LPS) and vascular dysfunction (in vitro and in vivo), production of pro-inflammatory cytokines, and iNOS expression and activity were evaluated. LPS-treated WT animals exhibited a marked fall in mean arterial blood pressure (MABP) whereas NPR-A KO mice maintained MABP throughout. LPS administration caused a greater suppression of vascular responses to the thromboxane-mimetic U46619, ANP, acetylcholine and the NO-donor spermine-NONOate in WT versus NPR-A KO mice. This differential effect on vascular function was paralleled by reduced pro-inflammatory cytokine production, iNOS expression and activity (plasma [NO(x)] and cyclic GMP). These observations suggest that NPR-A activation by natriuretic peptides facilitates iNOS expression and contributes to the vascular dysfunction characteristic of endotoxic shock. Pharmacological interventions that target the natriuretic peptide system may represent a novel approach to treat this life-threatening condition.

  10. Expression of brain natriuretic peptide by human bone marrow stromal cells.

    PubMed

    Song, S; Kamath, S; Mosquera, D; Zigova, T; Sanberg, P; Vesely, D L; Sanchez-Ramos, J

    2004-01-01

    Bone marrow stromal cells (BMSC) have been shown to generate neural cells under experimental conditions in vitro and following transplantation into animal models of stroke and traumatic CNS injury. Hastened recovery from the neurological deficit has not correlated with structural repair of the lesion in the stroke model. Secretory functions of BMSC, such as the elaboration of growth factors and cytokines, have been hypothesized to play a role in the enhanced recovery of neurological function. Using gene expression arrays, real time RT-PCR and radioimmunoassay, we have found that brain natriuretic peptide (BNP) is synthesized and released by BMSC at physiologically relevant levels in vitro. BNP, like its close homolog atrial natriuretic peptide (ANP), exerts powerful natriuretic, diuretic and vasodilatory effects. We speculate that transplanted BMSCs facilitate recovery from brain and spinal cord lesions by releasing BNP and other vasoactive factors that reduce edema, decrease intracranial pressure and improve cerebral perfusion.

  11. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy.

    PubMed

    Dunn, Michael E; Manfredi, Thomas G; Agostinucci, Kevin; Engle, Steven K; Powe, Josh; King, Nicholas M P; Rodriguez, Luis A; Gropp, Kathryn E; Gallacher, Matthew; Vetter, Frederick J; More, Vijay; Shimpi, Prajakta; Serra, David; Colton, Heidi M

    2017-02-01

    Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

  12. INTERACTING DISCIPLINES: Cardiac natriuretic peptides and obesity: perspectives from an endocrinologist and a cardiologist

    PubMed Central

    Ramos, Hugo R; Birkenfeld, Andreas L; de Bold, Adolfo J

    2015-01-01

    Since their discovery in 1981, the cardiac natriuretic peptides (cNP) atrial natriuretic peptide (also referred to as atrial natriuretic factor) and brain natriuretic peptide have been well characterised in terms of their renal and cardiovascular actions. In addition, it has been shown that cNP plasma levels are strong predictors of cardiovascular events and mortality in populations with no apparent heart disease as well as in patients with established cardiac pathology. cNP secretion from the heart is increased by humoral and mechanical stimuli. The clinical significance of cNP plasma levels has been shown to differ in obese and non-obese subjects. Recent lines of evidence suggest important metabolic effects of the cNP system, which has been shown to activate lipolysis, enhance lipid oxidation and mitochondrial respiration. Clinically, these properties lead to browning of white adipose tissue and to increased muscular oxidative capacity. In human association studies in patients without heart disease higher cNP concentrations were observed in lean, insulin-sensitive subjects. Highly elevated cNP levels are generally observed in patients with systolic heart failure or high blood pressure, while obese and type-2 diabetics display reduced cNP levels. Together, these observations suggest that the cNP system plays a role in the pathophysiology of metabolic vascular disease. Understanding this role should help define novel principles in the treatment of cardiometabolic disease. PMID:26115665

  13. Global left atrial failure in heart failure.

    PubMed

    Triposkiadis, Filippos; Pieske, Burkert; Butler, Javed; Parissis, John; Giamouzis, Gregory; Skoularigis, John; Brutsaert, Dirk; Boudoulas, Harisios

    2016-11-01

    The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  14. Atrial fibrillation down-regulates renal neutral endopeptidase expression and induces profibrotic pathways in the kidney.

    PubMed

    Bukowska, Alicja; Lendeckel, Uwe; Krohn, Alexander; Keilhoff, Gerburg; ten Have, Sara; Neumann, Klaus Hinrich; Goette, Andreas

    2008-10-01

    Recent studies suggest that atrial fibrillation (AF) substantially influences microvascular flow in ventricular myocardium. This process may contribute to the occurrence of heart failure in AF. In general, development of heart failure and renal dysfunction go hand-in-hand causing systemic fluid overload and oedema. So far, it is unknown whether AF itself influences renal function. The aim of the present study was to determine the impact of AF on renal gene expression in a closed chest rapid atrial pacing model. A total of 14 pigs were studied. In five pigs, rapid atrial pacing (AT) was performed for 7 h (600 bpm); in five additional animals, rapid atrial pacing was performed in the presence of irbesartan infusion (irbesartan group). Four pigs were instrumented without interventions (sham). After the pacing period, renal expression of collagen I alpha 1 and I alpha 3, transforming growth factor-beta (TGF-beta), neutral endopeptidase (NEP; the main enzyme involved in natriuretic protein metabolism), and atrial natriuretic peptide (ANP) were determined by RT-PCR and immunoblot analysis. Functional in vitro experiments were performed using HEK-293 kidney cells. Renal mRNA expression of NEP was substantially down-regulated during AT (AT: 12.7 +/- 9.3% vs. sham: 100 +/- 43.4%; P < 0.01). Results at the mRNA level were confirmed at the protein level. Irbesartan therapy did not prevent down-regulation of NEP. In contrast, TGF-beta1 mRNA expression was up-regulated (AT: 208.5 +/- 79.3% vs. sham: 100 +/- 34.6% P< 0.05). Collagen and angiotensin II type 1 receptor (AT1R) expression were not significantly altered by AT. HEK-293 cells were used to determine the potential humoral factors involved in down-regulation of NEP. Application of aldosterone, ANP, asymmetric dimethylarginine, and angiotensin peptides failed to cause down-regulation of renal NEP expression in vitro. AT reduces NEP expression and stimulates TGF-beta1 signalling in the kidneys. Thus, even brief episodes of

  15. Dendroaspis natriuretic peptide system and its paracrine function in rat colon.

    PubMed

    Kim, Jong Hun; Yang, Sung Hoon; Yu, Mo Young; Lee, Hye Kyung; Kim, So Young; Kim, Suhn Hee

    2004-08-15

    Dendroaspis natriuretic peptide (DNP), a 38-amino-acid peptide, was isolated from the venom of Green Mamba. It has structural and functional similarities to other members of the natriuretic peptide family. The purpose of this study was to determine whether DNP system is present in the rat colon and to define its biological functions. The serial dilution curve of extracts of colonic tissues was parallel to the standard curve of DNP and a major peak of molecular profile by HPLC was synthetic DNP. The concentration of DNP was 0.5 +/- 0.04 ng/g of colonic tissues. DNP as well as atrial natriuretic peptide and C-type natriuretic peptide caused dose-dependent increases in cGMP production in the purified membrane of colonic tissues. Three types of natriuretic peptide receptor mRNAs were detected using semi-quantitative RT-PCR. Functionally, synthetic DNP inhibited the spontaneous contraction of rat colonic circular muscle in a concentration-dependent manner. The potency appeared to be at least 10 times greater than that of CNP. Furthermore, DNP inhibited carbachol-induced muscle contraction, suggesting that it also can modulate the nerve regulation of colonic motility. This study demonstrates the presence of DNP system in rat colon and its function as a local regulator of colonic motility.

  16. Silent Atrial Fibrillation and Cryptogenic Strokes.

    PubMed

    Dalen, James E; Alpert, Joseph S

    2017-03-01

    A new suspected cause of cryptic strokes is "silent atrial fibrillation." Pacemakers and other implanted devices allow continuous recording of cardiac rhythm for months or years. They have discovered that short periods of atrial fibrillation lasting minutes or hours are frequent and usually are asymptomatic. A meta-analysis of 50 studies involving more than 10,000 patients with a recent stroke found that 7.7% had new atrial fibrillation on their admitting electrocardiogram. In 3 weeks during and after hospitalization, another 16.9% were diagnosed. A total of 23.7% of these stroke patients had silent atrial fibrillation; that is, atrial fibrillation diagnosed after hospital admission. Silent atrial fibrillation is also frequent in patients with pacemakers who do not have a recent stroke. In a pooled analysis of 3 studies involving more than 10,000 patients monitored for 24 months, 43% had at least 1 day with atrial fibrillation lasting more than 5 minutes. Ten percent had atrial fibrillation lasting at least 12 hours. Despite the frequency of silent atrial fibrillation in these patients with multiple risk factors for stroke, the annual incidence of stroke was only 0.23%. When silent atrial fibrillation is detected in patients with recent cryptogenic stroke, anticoagulation is indicated. In patients without stroke, silent atrial fibrillation should lead to further monitoring for clinical atrial fibrillation rather than immediate anticoagulation, as some have advocated.

  17. Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor

    SciTech Connect

    Johns, Douglas G. . E-mail: Douglas.G.Johns@gsk.com; Ao, Zhaohui; Heidrich, Bradley J.; Hunsberger, Gerald E.; Graham, Taylor; Payne, Lisa; Elshourbagy, Nabil; Lu, Quinn; Aiyar, Nambi; Douglas, Stephen A.

    2007-06-22

    Dendroaspis natriuretic peptide (DNP) is a newly-described natriuretic peptide which lowers blood pressure via vasodilation. The natriuretic peptide clearance receptor (NPR-C) removes natriuretic peptides from the circulation, but whether DNP interacts with human NPR-C directly is unknown. The purpose of this study was to test the hypothesis that DNP binds to NPR-C. ANP, BNP, CNP, and the NPR-C ligands AP-811 and cANP(4-23) displaced [{sup 125}I]-ANP from NPR-C with pM-to-nM K {sub i} values. DNP displaced [{sup 125}I]-ANP from NPR-C with nM potency, which represents the first direct demonstration of binding of DNP to human NPR-C. DNP showed high pM affinity for the GC-A receptor and no affinity for GC-B (K {sub i} > 1000 nM). DNP was nearly 10-fold more potent than ANP at stimulating cGMP production in GC-A expressing cells. Blockade of NPR-C might represent a novel therapeutic approach in augmenting the known beneficial actions of DNP in cardiovascular diseases such as hypertension and heart failure.

  18. Atrial Fibrillation

    MedlinePlus

    ... information about the heart's electrical system and detailed animations, go to the Diseases and Conditions Index How ... can't restore a normal heart rhythm. The animation below shows atrial fibrillation. Click the "start" button ...

  19. The usefulness of left atrial volume index and left ventricular mass index in determining subclinical cardiac involvement in patients with early-stage sarcoidosis.

    PubMed

    Kasapkara, H A; Şentürk, A; Bilen, E; Duran Karaduman, B; Ayhan, H; Özen, M B; Durmaz, T; Keleş, T; Bozkurt, E

    2016-08-01

    Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. The present study has been designed to evaluate the importance of diastolic dysfunction with left atrial volume index (LAVi) and left ventricular mass index (LVMi) in determining subclinical cardiac involvement in subjects with stage I-II pulmonary sarcoidosis. A total of 54 patients under follow-up for sarcoidosis without cardiac involvement and 56 healthy subjects were included in the study. The echocardiographic assessment of the patients revealed no significant difference between the two groups regarding left ventricular end-systolic and end-diastolic diameters, ejection fraction (LVEF) and annular velocity determined by tissue Doppler evaluation. The LVEF calculated was 61.8 ± 7.8 % in the sarcoidosis group versus 64.1 ± 2.7 % in the control group (p = 0.04). Left ventricular interventricular septum thickness, posterior wall thickness, and relative wall thickness were significantly higher in the sarcoidosis group compared to the control group (p < 0.001). The sarcoidosis group had higher LVM and LVMi values compared to the control group (145 ± 18.1 and 79 ± 14 g/m(2), 135 ± 27.7 and 74 ± 14.2 g/m(2); p = 0.020 and p = 0.021, respectively). Left atrial end-systolic volume and LAVi were higher in the sarcoidosis group (28.7 ± 18.5; 15.6 ± 10.2) compared to the control group (16.6 ± 10.9; 8.9 ± 5.5) with a statistically significant difference (p < 0.001). The present study indicates diastolic dysfunction and increased LVMi despite normal systolic function in patients with early-stage sarcoidosis without cardiac involvement. Also, the diastolic parameters were normal without showing any significant difference compared to the control group while there was a statistically significant increase in LAVi. This finding suggests that LAVi may be the earliest marker of diastolic dysfunction in patients with early-stage sarcoidosis without cardiac

  20. Radiofrequency Ablation of Persistent Atrial Fibrillation

    PubMed Central

    Hussein, Ayman A.; Saliba, Walid I.; Barakat, Amr; Bassiouny, Mohammed; Chamsi-Pasha, Mohammed; Al-Bawardy, Rasha; Hakim, Ali; Tarakji, Khaldoun; Baranowski, Bryan; Cantillon, Daniel; Dresing, Thomas; Tchou, Patrick; Martin, David O.; Varma, Niraj; Bhargava, Mandeep; Callahan, Thomas; Niebauer, Mark; Kanj, Mohamed; Chung, Mina; Natale, Andrea; Lindsay, Bruce D.; Wazni, Oussama M.

    2017-01-01

    Background Various ablation strategies of persistent atrial fibrillation (PersAF) have had disappointing outcomes, despite concerted clinical and research efforts, which could reflect progressive atrial fibrillation–related atrial remodeling. Methods and Results Two-year outcomes were assessed in 1241 consecutive patients undergoing first-time ablation of PersAF (2005–2012). The time intervals between the first diagnosis of PersAF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide and C-reactive protein before the procedures. The median diagnosis-to-ablation time was 3 years (25th–75th percentiles 1–6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in recurrence rates in addition to an increase in B-type natriuretic peptide levels (P=0.01), C-reactive protein levels (P<0.0001), and left atrial size (P=0.03). The arrhythmia recurrence rates over 2 years were 33.6%, 52.6%, 57.1%, and 54.6% in the first, second, third, and fourth quartiles, respectively (Pcategorical<0.0001). In Cox Proportional Hazard analyses, B-type natriuretic peptide levels, C-reactive protein levels, and left atrial size were associated with arrhythmia recurrence. The diagnosis-to-ablation time had the strongest association with the ablation outcomes which persisted in multivariable Cox analyzes (hazard ratio for recurrence per +1Log diagnosis-to-ablation time 1.27, 95% confidence interval 1.14–1.43; P<0.0001; hazard ratio fourth versus first quartile 2.44, 95% confidence interval 1.68–3.65; Pcategorical<0.0001). Conclusions In patients with PersAF undergoing ablation, the time interval between the first diagnosis of PersAF and the catheter ablation procedure had a strong association with the ablation outcomes, such as shorter diagnosis-to-ablation times were associated with better outcomes and in direct association with markers of atrial remodeling. PMID:26763227

  1. Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom.

    PubMed

    Da Silva, S L; Dias-Junior, C A; Baldasso, P A; Damico, D C S; Carvalho, B M A; Garanto, A; Acosta, G; Oliveira, E; Albericio, F; Soares, A M; Marangoni, S; Resende, R R

    2012-08-01

    Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand Canyon, United States of America. Knowledge regarding the composition of C. o. abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and characterized from the venoms of members of the Crotalinae family. The NP family comprises three members, ANP (atrial natriuretic peptide), BNP (b-type natriuretic peptide) and CNP (c-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. The aim of the present study was to characterize a novel natriuretic-like peptide (Coa_NP2), isolated from C. o. abyssus venom. The Coa_NP2 presents an average molecular mass of 3419.88Da (theoretical average molecular mass 3418.94Da, monoisotopic molecular mass 3416.66Da and theoretical PI 7.78) and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides. The peptide has 32 amino acids and its complete sequence is SYGISSGCFGLKLDRIGTMSGLGCWRLLQDSP. Coa_NP2 is a natriuretic peptide of the ANP/BNP-like family, since the carboxyterminal region of CNP has its own NP domain. We demonstrate, herein, that Coa_NP2 produces a dose-dependent decrease in mean arterial pressure in rats, followed by significant increases in concentrations of markers of nitric oxide formation measured in the plasma and vasorelaxation in a thoracic aortic ring bath. The structural and biological aspects confirm Coa_NP2 as a new natriuretic peptide, isolated from snake venom. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat

    PubMed Central

    Knight, Sarah; Snellen, Harold; Humphreys, Michael; Baylis, Chris

    2009-01-01

    Normal rat pregnancy is characterized by plasma volume expansion due to renal sodium retention and is associated with a blunted response to natriuretic stimuli, such as atrial natriuretic peptide (ANP). ANP signals via cGMP, and phosphodiesterases (PDE) inactivate cGMP and terminate the natriuretic response. We previously reported that increased medullary PDE-5 activity occurs in rat pregnancy, which may be the mechanism of the blunted natriuretic effect of ANP. Here, we used anesthetized 16-day pregnant and virgin rats to investigate whether intrarenal infusion of a selective PDE-5 inhibitor, sildenafil, would reverse the blunted response to ANP in pregnancy. We measured blood pressure, renal clearances using inulin and p-aminohippuric acid, and electrolyte excretion at baseline and during an ANP infusion. ANP caused a fall in mean arterial pressure in all groups, and sildenafil induced a further reduction. We observed an increase in sodium excretion with ANP in all rats, but this was blunted in the vehicle-infused pregnant rats. This could not be explained by differences in renal hemodynamics and was of tubular origin, as reflected by the reduced rise in fractional excretion of sodium with ANP in the pregnant rat given vehicle (45 ± 11 vs. 204 ± 49%; P < 0.05). However, intrarenal sildenafil increased the natriuretic response and the rise in fractional excretion of sodium to the virgin value (226 ± 23 vs. 245 ± 73%; not significant), whereas the blunting persisted in the contralateral kidney. This demonstrates that increased intrarenal PDE-5 mediates the blunted natriuretic response to ANP during pregnancy and may contribute to the physiological volume expansion. PMID:17003222

  3. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    SciTech Connect

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  4. Brain natriuretic peptide in acute ischemic stroke.

    PubMed

    Maruyama, Kenji; Shiga, Tsuyoshi; Iijima, Mutsumi; Moriya, Saori; Mizuno, Satoko; Toi, Sono; Arai, Kotaro; Ashihara, Kyomi; Abe, Kayoko; Uchiyama, Shinichiro

    2014-01-01

    Elevated serum brain natriuretic peptide (BNP) levels are associated with cardioembolic stroke mainly because of atrial fibrillation (AF). However, the mechanisms of increased serum BNP levels are hitherto unclear. We aimed to identify the factors associated with increased BNP levels in patients with acute ischemic stroke. We measured serum BNP levels in consecutive patients aged 18 years or older. Stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment criteria. Categorical variables included age, sex, smoking status, alcohol consumption status, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease (CAD), AF, antiplatelet therapy, and anticoagulant therapy. Continuous variables included hemoglobin, creatinine (Cr), β-thromboglobulin, platelet factor 4, thrombin-antithrombin complex, and d-dimer levels. We further determined the relationship between serum BNP and intima-media thickness, left ventricular ejection fraction, size of infarction, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale (mRS) score at discharge. Of the 231 patients (mean age, 71 ± 12 years) with acute ischemic stroke (AIS), 36% were women. Serum BNP levels significantly correlated with CAD, AF, Cr, mRS, and cardioembolism (CE) (Dunnett method, P = .004). BNP levels were significantly higher in patients with larger infarcts, higher mRS scores, and higher CHADS2 scores. The levels were higher in patients with larger infarcts, higher mRS scores at discharge, and higher CHADS2 scores among AF patients. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Natriuretic Hormones, Endogenous Ouabain, and Related Sodium Transport Inhibitors

    PubMed Central

    Hamlyn, John M.

    2014-01-01

    The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NHs). In addition to the atrial peptides (APs), the circulation contains unidentified physiologically relevant NHs. One NH is controlled by the central nervous system (CNS) and likely secreted by the pituitary. Its circulating activity is modulated by salt intake and the prevailing sodium concentration of the blood and intracerebroventricular fluid, and contributes to postprandial and dehydration natriuresis. The other NH, mobilized by atrial stretch, promotes natriuresis by increasing the production of intrarenal dopamine and/or nitric oxide (NO). Both NHs have short (<35 min) circulating half lives, depress renotubular sodium transport, and neither requires the renal nerves. The search for NHs led to endogenous cardiotonic steroids (CTS) including ouabain-, digoxin-, and bufadienolide-like materials. These CTS, given acutely in high nanomole to micromole amounts into the general or renal circulations, inhibit sodium pumps and are natriuretic. Among these CTS, only bufalin is cleared sufficiently rapidly to qualify for an NH-like role. Ouabain-like CTS are cleared slowly, and when given chronically in low daily nanomole amounts, promote sodium retention, augment arterial myogenic tone, reduce renal blood flow and glomerular filtration, suppress NO in the renal vasa recta, and increase sympathetic nerve activity and blood pressure. Moreover, lowering total body sodium raises circulating endogenous ouabain. Thus, ouabain-like CTS have physiological actions that, like aldosterone, support renal sodium retention and blood pressure. In conclusion, the mammalian circulation contains two non-AP NHs. Identification of the CNS NH should be a priority. PMID:25520702

  6. Molecular cloning of natriuretic peptide receptor A from bullfrog (Rana catesbeiana) brain and its functional expression.

    PubMed

    Sekiguchi, T; Miyamoto, K; Mizutani, T; Yamada, K; Yazawa, T; Yoshino, M; Minegishi, T; Takei, Y; Kangawa, K; Minamino, N; Saito, Y; Kojima, M

    2001-08-08

    A comparative study of natriuretic peptide receptor (NPR) was performed by cloning the NPR-A receptor subtype from the bullfrog (Rana catesbeiana) brain and analyzing its functional expression. Like other mammalian NPR-A receptors, the bullfrog NPR-A receptor consists of an extracellular ligand binding domain, a hydrophobic transmembrane domain, a kinase-like domain and a guanylate cyclase domain. Sequence comparison among the bullfrog and mammalian receptors revealed a relatively low ( approximately 45%) similarity in the extracellular domain compared to a very high similarity ( approximately 92%) in the cytoplasmic regulatory and catalytic domains. Expression of NPR-A mRNA was detected in various bullfrog tissues including the brain, heart, lung, kidney and liver; highest levels were observed in lung. Functional expression of the receptor in COS-7 cells revealed that frog atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) elicited cyclic guanosine 3'5'-monophosphate production by stimulating the receptor in a dose-dependent manner from 10(-10) M concentrations. Rat ANP was also effective in stimulating the frog receptor whereas rat BNP and porcine BNP were less responsive to the receptor. On the other hand, frog C-type natriuretic peptide (CNP) as well as porcine CNP stimulated the receptor only at high concentrations (10(-7) M). This clearly indicates that the bullfrog receptor is a counterpart of mammalian NPR-A, and is specific for ANP or BNP but not for CNP.

  7. Natriuretic Peptide Receptor A as a Novel Target for Prostate Cancer

    PubMed Central

    2011-01-01

    Background The receptor for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in prostate cancer remains unclear. Results NPRA expression was examined by western blotting, RT-PCR and immunohistochemistry. NPRA was downregulated by transfection of siRNA, shRNA and NPRA inhibitor (iNPRA). Antitumor efficacy of iNPRA was tested in mice using a TRAMP-C1 xenograft. Here, we demonstrated that NPRA is abundantly expressed on tumorigenic mouse and human prostate cells, but not in nontumorigenic prostate epithelial cells. NPRA expression showed positive correlation with clinical staging in a human PCa tissue microarray. Down-regulation of NPRA by siNPRA or iNPRA induced apoptosis in PCa cells. The mechanism of iNPRA-induced anti-PCa effects was linked to NPRA-induced expression of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine over-expressed in PCa and significantly reduced by siNPRA. Prostate tumor cells implanted in mice deficient in atrial natriuretic peptide receptor A (NPRA-KO) failed to grow, and treatment of TRAMP-C1 xenografts with iNPRA reduced tumor burden and MIF expression. Using the TRAMP spontaneous PCa model, we found that NPRA expression correlated with MIF expression during PCa progression. Conclusions Collectively, these results suggest that NPRA promotes PCa development in part by regulating MIF. Our findings also suggest that NPRA is a potential prognostic marker and a target for PCa therapy. PMID:21586128

  8. Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients.

    PubMed

    Haufe, Sven; Kaminski, Jana; Utz, Wolfgang; Haas, Verena; Mähler, Anja; Daniels, Martin A; Birkenfeld, Andreas L; Lichtinghagen, Ralf; Luft, Friedrich C; Schulz-Menger, Jeanette; Engeli, Stefan; Jordan, Jens

    2015-07-01

    Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients. Venous mid-regional pro-ANP concentration was assessed at rest and after incremental exhaustive exercise testing before and after weight reduction. We also measured natriuretic peptide receptor A and C mRNA expression in subcutaneous adipose tissue to gauge both ANP responsiveness and clearance mechanisms. The average weight reduction of 9.1 ± 3.8  kg was associated with reductions in visceral and subcutaneous abdominal fat mass, liver fat content, insulin resistance, and ambulatory blood pressure. However, mid-regional pro-ANP plasma concentrations were unchanged with weight loss (51 ± 24 vs. 53 ± 24  pmol/l). Exercise elicited similar acute mid-regional pro-ANP increases before and after weight loss. Adipose tissue natriuretic peptide receptor type A mRNA expression remained unchanged, whereas natriuretic peptide receptor type C mRNA decreased with weight loss. We conclude that physical exercise acutely increases ANP release in obese patients, whereas modest diet-induced weight loss primarily affects ANP clearance mechanisms. Interventions combining weight loss and regular physical exercise may be particularly efficacious in reversing obesity-associated relative natriuretic peptide deficiency.

  9. Atrial Fibrillation: Complications

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Complications Past Issues / Winter 2015 Table of Contents ... two major complications—stroke and heart failure. Atrial Fibrillation and Stroke Click to enlarge image This illustration ...

  10. Atrial Fibrillation: Treatment

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Treatment Past Issues / Winter 2015 Table of Contents Treatment for atrial fibrillation depends on how often you have symptoms, how ...

  11. Natriuretic peptides in water-deprived and in salt-loaded rats.

    PubMed

    Makino, Y; Minamino, N; Kakishita, E; Kangawa, K; Matsuo, H

    1996-01-01

    To elucidate the differences of physiological function of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), we measured tissue concentration and mRNA level in cardiac atrium, ventricle, and brain as well as plasma concentration of these three peptides in water-deprived (WD) and in salt-loaded (SI.) rats. WD rats were given no water for 5 days, whereas SL rats had free access to 2% saline for 14 days. Plasma ANP and BNP concentration of the WD group decreased to 21% and < 10%, and the concentration of the SL group to 36% and 47% of the control (CON) group. Atrial and ventricular BNP concentration of the WD group decreased to 36% and 23% of the CON group, and atrial BNP concentration of the SL group decreased to a lesser extent. BNP mRNA level in atrium and ventricle decreased in both the WD and SL groups, with the WD group showing larger decreases to 11% and 20% of the CON group. ANP mRNA level in atrium and ventricle of the WD group decreased to 40% and 61% of the CON group, but increased to 147% in ventricle of the SL group. In the brain, no significant change was observed in ANP and CNP concentration in both the WD and SL group. Under these conditions. BNP generally showed larger changes than ANP in both peptide concentration and mRNA level. Gene transcription and peptide production of ANP and BNP in atrium and in ventricle were not always found to be in concert, especially in the case of salt loading. Taken as a whole, our results demonstrate differences among the systems regulating biosynthesis and secretion of ANP and BNP in atrium and ventricle.

  12. Natriuretic Hormones in Brain Function

    PubMed Central

    Hodes, Anastasia; Lichtstein, David

    2014-01-01

    Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed. PMID:25506340

  13. Atrial Fibrillation.

    PubMed

    Zimetbaum, Peter

    2017-03-07

    This issue provides a clinical overview of atrial fibrillation, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  14. Giant right atrial thrombi treated with thrombolysis

    PubMed Central

    Ruiz-Bailén, Manuel; López-Caler, Carmen; Castillo-Rivera, Ana; Rucabado-Aguilar, Luis; Cuadra, José Ángel Ramos; Toral, Juan Lara; Cabezas, Cristobal Lozano; Guerrero, Juan Carlos Fernández

    2008-01-01

    The present report describes giant atrial thrombi that were treated with thrombolysis in a community hospital. Two patients with giant atrial thrombi whose treatment involved complications are presented. Both patients developed cardiogenic shock and were treated unsuccessfully with thrombolysis. Because thrombolysis of giant thrombi may be ineffective, patients in this situation may require surgery. PMID:18401474

  15. Giant right atrial thrombi treated with thrombolysis.

    PubMed

    Ruiz-Bailén, Manuel; López-Caler, Carmen; Castillo-Rivera, Ana; Rucabado-Aguilar, Luis; Ramos Cuadra, José Angel; Lara Toral, Juan; Lozano Cabezas, Cristobal; Fernández Guerrero, Juan Carlos

    2008-04-01

    The present report describes giant atrial thrombi that were treated with thrombolysis in a community hospital. Two patients with giant atrial thrombi whose treatment involved complications are presented. Both patients developed cardiogenic shock and were treated unsuccessfully with thrombolysis. Because thrombolysis of giant thrombi may be ineffective, patients in this situation may require surgery.

  16. Changes of adrenomedullin and natriuretic peptides in patients with adrenal medullary hyperplasia prior to and following pharmacological therapy and adrenalectomy

    PubMed Central

    Zhou, Pang-Hu; Shi, Lei; Hu, Wei; Zhang, Xiao-Bin; Wang, Wei; Zhang, Li-Jun

    2016-01-01

    The aim of the present study was to investigate the pathophysiological functions of adrenomedullin (ADM), atrial and brain natriuretic peptides (ANP and BNP) in patients with adrenal medullary hyperplasia (AMH). Plasma ADM, ANP and BNP concentrations were measured in 20 patients with AMH, 35 patients with essential hypertension (EH), and 40 healthy control subjects. Following effective antihypertensive therapy, the values in AMH and EH patients were measured again and laparoscopic adrenalectomy was performed for AMH patients. At 2 weeks after surgery, the three peptides were measured again. The AMH patients had higher plasma concentrations of ADM, ANP and BNP compared with the EH and control subjects. There were significant differences in the values of ADM, ANP and BNP between adrenal vein and inferior vena cava and between AMH and contralateral adrenal vein. Plasma ADM concentration was correlated with serum epinephrine and norepinephrine and urine vanillylmandelic acid, in addition to systolic and diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and ANP and BNP values in the AMH group. Following antihypertensive treatment, ADM, ANP and BNP were significantly decreased in EH patients, but remained unchanged in AMH subjects. However, these concentrations significantly decreased following surgery. Therefore, the present results suggest that ADM, ANP and BNP may be involved in regulating adrenal medulla functions. PMID:27446289

  17. Atrial fibrillation

    PubMed Central

    Munger, Thomas M.; Wu, Li-Qun; Shen, Win K.

    2014-01-01

    Atrial fibrillation is the most common arrhythmia affecting patients today. Disease prevalence is increasing at an alarming rate worldwide, and is associated with often catastrophic and costly consequences, including heart failure, syncope, dementia, and stroke. Therapies including anticoagulants, anti-arrhythmic medications, devices, and non-pharmacologic procedures in the last 30 years have improved patients' functionality with the disease. Nonetheless, it remains imperative that further research into AF epidemiology, genetics, detection, and treatments continues to push forward rapidly as the worldwide population ages dramatically over the next 20 years. PMID:24474959

  18. Molecular Basis of Gene-Gene Interaction: Cyclic Cross-Regulation of Gene Expression and Post-GWAS Gene-Gene Interaction Involved in Atrial Fibrillation.

    PubMed

    Huang, Yufeng; Wang, Chuchu; Yao, Yufeng; Zuo, Xiaoyu; Chen, Shanshan; Xu, Chengqi; Zhang, Hongfu; Lu, Qiulun; Chang, Le; Wang, Fan; Wang, Pengxia; Zhang, Rongfeng; Hu, Zhenkun; Song, Qixue; Yang, Xiaowei; Li, Cong; Li, Sisi; Zhao, Yuanyuan; Yang, Qin; Yin, Dan; Wang, Xiaojing; Si, Wenxia; Li, Xiuchun; Xiong, Xin; Wang, Dan; Huang, Yuan; Luo, Chunyan; Li, Jia; Wang, Jingjing; Chen, Jing; Wang, Longfei; Wang, Li; Han, Meng; Ye, Jian; Chen, Feifei; Liu, Jingqiu; Liu, Ying; Wu, Gang; Yang, Bo; Cheng, Xiang; Liao, Yuhua; Wu, Yanxia; Ke, Tie; Chen, Qiuyun; Tu, Xin; Elston, Robert; Rao, Shaoqi; Yang, Yanzong; Xia, Yunlong; Wang, Qing K

    2015-08-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for <10% of heritability. Gene-gene interaction is assumed to account for a significant portion of missing heritability. Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1. Thus, we analyzed the interaction among these three AF loci. We demonstrated significant interaction between rs2106261 and rs2200733 in three independent populations and combined population with 2,020 cases/5,315 controls. Compared to non-risk genotype GGCC, two-locus risk genotype AATT showed the highest odds ratio in three independent populations and the combined population (OR=5.36 (95% CI 3.87-7.43), P=8.00×10-24). The OR of 5.36 for AATT was significantly higher than the combined OR of 3.31 for both GGTT and AACC, suggesting a synergistic interaction between rs2106261 and rs2200733. Relative excess risk due to interaction (RERI) analysis also revealed significant interaction between rs2106261 and rs2200733 when exposed two copies of risk alleles (RERI=2.87, P<1.00×10-4) or exposed to one additional copy of risk allele (RERI=1.29, P<1.00×10-4). The INTERSNP program identified significant genotypic interaction between rs2106261 and rs2200733 under an additive by additive model (OR=0.85, 95% CI: 0.74-0.97, P=0.02). Mechanistically, PITX2c negatively regulates expression of miR-1, which negatively regulates expression of ZFHX3, resulting in a positive regulation of ZFHX3 by PITX2c; ZFHX3 positively regulates expression of PITX2C, resulting in a cyclic loop of cross-regulation between ZFHX3 and PITX2c. Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. These results suggest that cyclic cross-regulation of gene expression is a molecular basis for gene

  19. Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function.

    PubMed Central

    Bonarjee, V. V.; Omland, T.; Nilsen, D. W.; Caidahl, K.; Sundsfjord, J. A.; Dickstein, K.

    1995-01-01

    OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection

  20. Ablation for Atrial Fibrillation

    PubMed Central

    2006-01-01

    Executive Summary Objective To review the effectiveness, safety, and costing of ablation methods to manage atrial fibrillation (AF). The ablation methods reviewed were catheter ablation and surgical ablation. Clinical Need Atrial fibrillation is characterized by an irregular, usually rapid, heart rate that limits the ability of the atria to pump blood effectively to the ventricles. Atrial fibrillation can be a primary diagnosis or it may be associated with other diseases, such as high blood pressure, abnormal heart muscle function, chronic lung diseases, and coronary heart disease. The most common symptom of AF is palpitations. Symptoms caused by decreased blood flow include dizziness, fatigue, and shortness of breath. Some patients with AF do not experience any symptoms. According to United States data, the incidence of AF increases with age, with a prevalence of 1 per 200 people aged between 50 and 60 years, and 1 per 10 people aged over 80 years. In 2004, the Institute for Clinical Evaluative Sciences (ICES) estimated that the rate of hospitalization for AF in Canada was 582.7 per 100,000 population. They also reported that of the patients discharged alive, 2.7% were readmitted within 1 year for stroke. One United States prevalence study of AF indicated that the overall prevalence of AF was 0.95%. When the results of this study were extrapolated to the population of Ontario, the prevalence of AF in Ontario is 98,758 for residents aged over 20 years. Currently, the first-line therapy for AF is medical therapy with antiarrhythmic drugs (AADs). There are several AADs available, because there is no one AAD that is effective for all patients. The AADs have critical adverse effects that can aggravate existing arrhythmias. The drug selection process frequently involves trial and error until the patient’s symptoms subside. The Technology Ablation has been frequently described as a “cure” for AF, compared with drug therapy, which controls AF but does not cure it

  1. Navx-guided Cryoablation of Atrial Tachycardia Inside the Left Atrial Appendage

    PubMed Central

    Pandozi, Claudio; Galeazzi, Marco; Lavalle, Carlo; Ficili, Sabina; Russo, Maurizio; Santini, Massimo

    2010-01-01

    Radiofrequency ablation procedures inside the left atrial appendage (LAA) are likely to involve dangerous complications because of a high thrombogenic effect. Cryoablation procedures are supposed to be safer. We describe two cases of successful cryoablation procedures. Two NavX-guided cryoablations of permanent focal atrial arrhythmias arising from the LAA were performed. Left atrial reconstruction and mapping allowed the zone of the earliest atrial potential to be recorded; the entire course of the ablation catheter was monitored. The arrhythmias were successfully ablated; no thrombotic complications were observed. PMID:21346824

  2. Late atypical atrial flutter after ablation of atrial fibrillation.

    PubMed

    Ferreira, Raquel; Primo, João; Adão, Luís; Gonzaga, Anabela; Gonçalves, Helena; Santos, Rui; Fonseca, Paulo; Santos, José; Gama, Vasco

    2016-10-01

    Cardiac surgery for structural heart disease (often involving the left atrium) and radiofrequency catheter ablation of atrial fibrillation have led to an increased incidence of regular atrial tachycardias, often presenting as atypical flutters. This type of flutter is particularly common after pulmonary vein isolation, especially after extensive atrial ablation including linear lesions and/or defragmentation. The authors describe the case of a 51-year-old man, with no relevant medical history, referred for a cardiology consultation in 2009 for paroxysmal atrial fibrillation. After failure of antiarrhythmic therapy, he underwent catheter ablation, with criteria of acute success. Three years later he again suffered palpitations and atypical atrial flutter was documented. The electrophysiology study confirmed the diagnosis of atypical left flutter and reappearance of electrical activity in the right inferior pulmonary vein. This vein was again ablated successfully and there has been no arrhythmia recurrence to date. In an era of frequent catheter ablation it is essential to understand the mechanism of this arrhythmia and to recognize such atypical flutters. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Sacubitril/valsartan: beyond natriuretic peptides.

    PubMed

    Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

    2017-07-08

    Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

  4. Relation of Natriuretic Peptide Concentrations to Central Sleep Apnea in Patients With Heart Failure

    PubMed Central

    Calvin, Andrew D.; Somers, Virend K.; van der Walt, Christelle; Scott, Christopher G.

    2011-01-01

    Background: Central sleep apnea (CSA) is frequent among patients with heart failure (HF) and associated with increased morbidity and mortality. Elevated cardiac filling pressures promote CSA and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. We hypothesized that circulating natriuretic peptide concentrations predict CSA. Methods: Consecutive patients with HF (n = 44) with left ventricular ejection fraction (LVEF) ≤ 35% underwent polysomnography for detection of CSA. CSA was defined as an apnea-hypopnea index ≥ 15 with ≥ 50% central apneic events. The relation of natriuretic peptide concentrations to CSA was evaluated by estimation of ORs and receiver operator characteristics (ROCs). Results: Twenty-seven subjects (61%) had CSA, with men more frequently affected than women (73% vs 27%; OR, 7.1; P = .01); given that only three women had CSA, further analysis was restricted to men. Subjects with CSA had higher mean ANP (4,336 pg/mL vs 2,510 pg/mL, P = .03) and BNP concentrations (746 pg/mL vs 379 pg/mL, P = .05). ANP and BNP concentrations were significantly related to CSA (OR, 3.7 per 3,000 pg/mL, P = .03 and OR, 1.5 per 200 pg/mL, P = .04, respectively), whereas age, LVEF, and New York Heart Association functional class were not. Concentrations of ANP and BNP were predictive of CSA as ROC demonstrated areas under the curve of 0.75 and 0.73, respectively. Conclusions: Risk of CSA is related to severity of HF. ANP and BNP concentrations performed similarly for detection of CSA; low concentrations appear associated with low risk for CSA in men. PMID:21636668

  5. Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

    SciTech Connect

    Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S.

    2011-06-01

    Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.

  6. Natriuretic peptides as regulatory mediators of secretory activity in the digestive system.

    PubMed

    Sabbatini, Maria Eugenia

    2009-04-10

    Atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are members of the natriuretic peptide family best known for their role in blood pressure regulation. However, in recent years all the natriuretic peptides and their receptors have been described in the gastrointestinal tract, digestive glands and central nervous system, as well as implicated in the regulation of digestive gland functions. The current review highlights the regulatory role of ANP and CNP in pancreatic and other digestive secretions. ANP and CNP stimulate basal as well as induced pancreatic secretion and modify bicarbonate and chloride secretions. Whereas ANP and CNP exert effects directly on pancreatic cells, CNP also acts through a vago-vagal reflex. At high doses both peptides attenuate pancreatic secretion induced by high doses of secretin through the PLC/PKC pathway. With regards to other digestive secretions, ANP and CNP decrease bile secretion in the rat. ANP does not induce salivation by itself but enhances stimulated salivary secretion and modifies salivary composition in rat parotid as well as submandibular glands. In rat pancreatic, hepatic, parotid and submandibular tissues, the NPR-C receptor mediates mostly peripheral responses whereas NPR-A and NPR-B receptors, which are coupled to guanylate cyclase, likely mediate the central response. In addition, ANP modulates gastric acid secretion via a vagal-dependent mechanism. In the intestine, ANP and CNP decrease water and sodium chloride absorption through an increase in cGMP levels. Overall, these findings indicate that ANP and CNP are members of the large group of regulatory peptides affecting digestive secretions.

  7. Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy.

    PubMed

    Pagel-Langenickel, Ines; Buttgereit, Jens; Bader, Michael; Langenickel, Thomas H

    2007-08-01

    Natriuretic peptides (NP) represent a family of structurally homologous but genetically distinct peptide hormones involved in regulation of fluid and electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR-B) signaling in regulation of cardiac growth by either a direct effect on cardiomyocytes or by modulation of other signaling pathways including the autonomic nervous system. The research links NPR-B for the first time to a cardiac phenotype in vivo and underlines the importance of the NP in the cardiovascular system. This manuscript will focus on the role of NPR-B and its ligand C-type natriuretic peptide in cardiovascular physiology and disease and will evaluate these new findings in the context of the known function of this receptor, with a perspective on how future research might further elucidate NPR-B function.

  8. Brain natriuretic peptide predicts mortality in the elderly.

    PubMed Central

    Wallén, T.; Landahl, S.; Hedner, T.; Nakao, K.; Saito, Y.

    1997-01-01

    OBJECTIVE: To study whether prospective measurements of circulating concentrations of brain natriuretic peptide (BNP) could predict mortality in the general elderly population. DESIGN AND SETTING: Circulating BNP was measured in a cohort of 85 year olds from the general population who were followed up prospectively for five years as part of a longitudinal population study, "70 year old people in Gothenburg, Sweden". PATIENTS: 541 subjects from the 85 year old population in Gothenburg. All subjects were investigated for the presence or absence of cardiovascular disorder such as congestive heart failure, ischaemic heart disease, hypertension, and atrial fibrillation. Venous plasma samples were obtained for BNP analysis. MAIN OUTCOME MEASURE: Overall mortality during the prospective follow up period. RESULTS: Circulating concentrations of BNP predicted five-year mortality in the total population (P < 0.001). In subjects with a known cardiovascular disorder, five-year mortality was correlated with increased BNP concentrations (P < 0.01). Increased BNP concentrations predicted five-year mortality in subjects without a defined cardiovascular disorder (P < 0.05). CONCLUSIONS: In an elderly population, measurements of BNP may add valuable prognostic information and may be used to predict mortality in the total population as well as in patients with known cardiovascular disorders. In subjects without any known cardiovascular disorder, BNP was a strong and independent predictor of total mortality. PMID:9093047

  9. What Is Atrial Fibrillation?

    MedlinePlus

    ANSWERS by heart Cardiovascular Conditions What Is Atrial Fibrillation? Your heart has a natural pacemaker, called the “ ... if the electric signals are normal. In atrial fibrillation (AFib), the heart’s two small upper chambers (atria) ...

  10. Atrial fibrillation or flutter

    MedlinePlus

    ... atrial fibrillation include: Alcohol use (especially binge drinking) Coronary artery disease Heart attack or heart bypass surgery Heart failure ... low. An ECG (a test that records the electrical activity of the heart) may show atrial fibrillation ...

  11. Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli.

    PubMed

    Woodard, Geoffrey E; Li, Xiaohong; Rosado, Juan A

    2004-09-01

    This study investigates the effect of water deprivation on the expression of atrial natiruretic peptide (ANP)(1-28) binding sites in rat kidney. Water deprivation increased the B(max) of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide (CNP)(1-22) without modifying their affinity, an effect that was prevented in the presence of C-atrial natriuretic factor (C-ANF), suggesting that natriuretic peptide receptor-C (NPR-C) binding sites might be enhanced. Our results indicate that ANP(1-28), CNP(1-22), and C-ANF inhibit cAMP synthesis directly stimulated by forskolin or by the physiological agonists histamine and 5-hydroxytryptamine. The inhibitory effect was found to be significantly greater in water-deprived rats than in controls. Our observations suggest that this effect must be attributed to the 67-kDa NPR-C-like protein, because the 67- and 77-kDa NPR-C-like proteins show high and low affinities for CNP(1-22), respectively, and the enhanced inhibitory effect of CNP on cAMP generation in water-deprived rats was detected at subnanomolar concentrations. In addition, using affinity cross-linking studies we have observed that water deprivation increases the expression of the 67-kDa NPR-C-like protein, and HS-142, which binds to NPR-A and the 77-kDa NPR-C-like but not the 67-kDa protein, reduced ligand internalization without affecting cAMP inhibition by ANP(1-28). Finally, we have found that ligand binding to the 67-kDa NPR-C-like protein is reduced by GTPgammaS, suggesting that this receptor is associated with a G protein in renal glomeruli. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis induced by water deprivation may influence glomerular function in the rat kidney.

  12. Elevated levels of natriuretic peptides in patients with pulmonary thromboembolism.

    PubMed

    Kiely, David G; Kennedy, Norman S; Pirzada, Omar; Batchelor, Sheila A; Struthers, Allan D; Lipworth, Brian J

    2005-10-01

    Pulmonary thromboembolism (PTE) occurs in a wide variety of clinical settings and presents a diagnostic challenge to clinicians, often requiring extensive imaging of the vascular bed. Management increasingly requires accurate risk stratification to rapidly identify those with massive and submassive PTE requiring different therapeutic strategies such as thrombolysis. Provision of a rapid blood test that improves diagnostic certainty and helps stratify risk could therefore bridge the gap between uncertainty and delivery of immediate early life-saving treatment. One hundred and fourteen consecutive patients with suspected PTE underwent prospective evaluation. Venous blood samples were obtained from an unselected group referred for ventilation-perfusion scintigraphy. B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and N-terminal pro-ANP (N-ANP) were measured by radioimmunoassay using commercially available kits. The scans were classified into three groups according to standard criteria (PIOPED); normal scan (N) (n=20), low/intermediate probability (L/I) of PTE (n=77) and high probability (H) of PTE (n=17). Comparisons were also made between patients with high probability scans who died (n=3) and those who survived (n=14). Values are quoted for the median and interquartile ranges. There were statistically significant differences between groups for levels of (a) BNP (P<0.001): N=6.7 pmol/l (5.6-11.9), L/I=12.5 pmol/l (6.7-28.2) and H=18.5 pmol/l (12.6-74.6); (b) ANP (P<0.005): N=12.6 pmol/l (7.1-16.0), L/I=19.51 pmol/l (12.5-28.2) and H=19.1 pmol/l (15.7-31.7) and (c) N-ANP (P<0.05): N=177 pmol/l (119-200), L/I=302 pmol/l (152-576) and H=322 pmol/l (223-563). Levels of BNP and ANP were significantly (P<0.05) higher in patients with high probability scans and a diagnosis of PTE who died (n=3) than in those who survived (n=14); BNP: 91.6 pmol/l (77.5-336.2) vs. 14.4 pmol/l (11.9-27.4) and ANP 32.5 pmol/l (21.7-105.5) vs. 17.6 pmol/l (15

  13. [Atrial fibrillation].

    PubMed

    Colín Lizalde, L J

    2001-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia. AF has now been exhaustively studied: more is known about its mechanism and research is moving towards new forms of treatment. For chronic AF, basically the control of ventricular rate and the brain protection are the main issues. It is well known that with the identification of high risk group for embolism, oral anticoagulation should be administered. Ventricular rate control can be achieved by using betablockers or calcium channel blockers, unless these are contraindicated for the elderly. Oral anticoagulation prevents the stroke. The main mechanism of AF is the re-entry of multiple wavelets, but now it is more frequently found on patients with focal AF. Therapies are employed to bring the patient to a sinusal rhythm as soon as possible with antiarryhthmics or electric cardioversion externally or internally. The internal procedure includes 1 to 15 J and the success rate is of 91% vs 67% in relation to the external one. The introduction of the catheter ablation has opened new frontiers for the treatment of AF, first as the ablate-and-pace technique and now trying to mimic the maze procedure or with the ablation of the focal tachycardia. The stimulation for prevention of AF under research, as well as the implantable dysfibrillation for selected patients. On going studies will show the possible benefit of this type of benefits.

  14. Brain natriuretic peptide: what the nurse needs to know.

    PubMed

    Nicholson, Christopher

    2017-05-17

    Rationale and key points Brain natriuretic peptide is a chemical secreted when the heart is under strain. It is sampled by a blood test. This article informs nurses about how brain natriuretic peptide can be used as a diagnostic and prognostic marker for patients with cardiac conditions. » A brain natriuretic peptide level within the normal range in a patient who is not receiving treatment, almost certainly rules out a significant cardiac condition. » An elevated brain natriuretic peptide level suggests an active cardiac condition and further investigations are indicated, usually an electrocardiogram and echocardiogram. » A highly elevated brain natriuretic peptide level is a marker for a more severe prognosis.

  15. Effect of natriuretic peptide family on the oxidized LDL-induced migration of human coronary artery smooth muscle cells.

    PubMed

    Kohno, M; Yokokawa, K; Yasunari, K; Kano, H; Minami, M; Ueda, M; Yoshikawa, J

    1997-10-01

    The migration of medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in atherosclerotic lesions. The present study examined the possible effect of a novel endothelium-derived relaxing peptide, C-type natriuretic peptide (CNP), on oxidized low-density lipoprotein (LDL)-induced migration of cultured human coronary artery SMCs by the Boyden's chamber method. The effect of CNP was compared with that of atrial and brain natriuretic peptides (ANP and BNP, respectively). Oxidized LDL stimulates SMC migration in a concentration-dependent manner between 20 and 200 micrograms/mL. This stimulation was chemotactic in nature but was not chemokinetic. By contrast, native LDL was without significant activity. CNP-22 clearly inhibited SMC migration stimulated with 200 micrograms/mL oxidized LDL in a concentration-dependent manner between 10(-9) and 10(-6) mol/L. ANP-(1-28) and BNP-32 also inhibited oxidized LDL-induced SMC migration at concentrations of 10(-7) and 10(-6) mol/L, but these effects were weaker than the effect of CNP-22. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. Oxidized LDL-induced migration was significantly inhibited by a stable analogue of cGMP, 8-bromo-cGMP, or an activator of the cytosolic guanylate cyclase, sodium nitroprusside. These natriuretic peptides did not suppress the cell adhesion either in the absence or presence of oxidized LDL. These data indicate that oxidized LDL stimulates migration of human coronary artery SMCs and that natriuretic peptides, especially CNP, inhibit this stimulated SMC migration, at least in part, through a cGMP-dependent process. Taken together with the finding that oxidized LDL is present in the intima, CNP may play a role as a local antimigration factor during the process of intimal thickening in hypercholesterolemia-induced coronary atherosclerosis.

  16. Natriuretic peptides modify Pseudomonas fluorescens cytotoxicity by regulating cyclic nucleotides and modifying LPS structure

    PubMed Central

    Veron, Wilfried; Orange, Nicole; Feuilloley, Marc GJ; Lesouhaitier, Olivier

    2008-01-01

    Background Nervous tissues express various communication molecules including natriuretic peptides, i.e. Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP). These molecules share structural similarities with cyclic antibacterial peptides. CNP and to a lesser extent BNP can modify the cytotoxicity of the opportunistic pathogen Pseudomonas aeruginosa. The psychrotrophic environmental species Pseudomonas fluorescens also binds to and kills neurons and glial cells, cell types that both produce natriuretic peptides. In the present study, we investigated the sensitivity of Pseudomonas fluorescens to natriuretic peptides and evaluated the distribution and variability of putative natriuretic peptide-dependent sensor systems in the Pseudomonas genus. Results Neither BNP nor CNP modified P. fluorescens MF37 growth or cultivability. However, pre-treatment of P. fluorescens MF37 with BNP or CNP provoked a decrease of the apoptotic effect of the bacterium on glial cells and an increase of its necrotic activity. By homology with eukaryotes, where natriuretic peptides act through receptors coupled to cyclases, we observed that cell-permeable stable analogues of cyclic AMP (dbcAMP) and cyclic GMP (8BcGMP) mimicked the effect of BNP and CNP on bacteria. Intra-bacterial concentrations of cAMP and cGMP were measured to study the involvement of bacterial cyclases in the regulation of P. fluorescens cytotoxicity by BNP or CNP. BNP provoked an increase (+49%) of the cAMP concentration in P. fluorescens, and CNP increased the intra-bacterial concentrations of cGMP (+136%). The effect of BNP and CNP on the virulence of P. fluorescens was independent of the potential of the bacteria to bind to glial cells. Conversely, LPS extracted from MF37 pre-treated with dbcAMP showed a higher necrotic activity than the LPS from untreated or 8BcGMP-pre-treated bacteria. Capillary electrophoresis analysis suggests that these different effects of the LPS may be due, at least in part, to

  17. Systemic, but not cardiomyocyte-specific, deletion of the natriuretic peptide receptor guanylyl cyclase A increases cardiomyocyte number in neonatal mice.

    PubMed

    Schipke, Julia; Roloff, Konstanze; Kuhn, Michaela; Mühlfeld, Christian

    2015-10-01

    Guanylyl cyclase A (GC-A), the receptor for atrial and B-type natriuretic peptides, is implicated in the regulation of blood pressure and cardiac growth. We used design-based stereological methods to examine the effect of GC-A inactivation on cardiomyocyte volume, number and subcellular composition in postnatal mice at day P2. In mice with global, systemic GC-A deletion, the cardiomyocyte number was significantly increased, demonstrating that hyperplasia is the main cause for the increase in ventricle weight in these early postnatal animals. In contrast, conditional, cardiomyocyte-restricted inactivation of GC-A had no significant effect on ventricle weight or cardiomyocyte number. The mean volume of cardiomyocytes and the myocyte-related volumes of the four major cell organelles (myofibrils, mitochondria, nuclei and sarcoplasm) were similar between genotypes. Taken together, systemic GC-A deficiency induces cardiac enlargement based on a higher number of normally composed and sized cardiomyocytes early after birth, whereas cardiomyocyte-specific GC-A abrogation is not sufficient to induce cardiac enlargement and has no effect on number, size and composition of cardiomyocytes. We conclude that postnatal cardiac hyperplasia in mice with global GC-A inactivation is provoked by systemic alterations, e.g., arterial hypertension. Direct GC-A-mediated effects in cardiomyocytes seem not to be involved in the regulation of myocyte proliferation at this early stage.

  18. How Is Atrial Fibrillation Treated?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Atrial Fibrillation Treated? Treatment for atrial fibrillation (AF) depends on ... much thyroid hormone). Who Needs Treatment for Atrial Fibrillation? People who have AF but don't have ...

  19. Molecular cloning of natriuretic peptides from the heart of reptiles: loss of ANP in diapsid reptiles and birds.

    PubMed

    Trajanovska, Sofie; Donald, John A

    2008-04-01

    Atrial natriuretic peptide (ANP) and B-type NP (BNP) are hormones involved in homeostatic control of body fluid and cardiovascular regulation. Both ANP and BNP have been cloned from the heart of mammals, amphibians, and teleost fishes, while an additional cardiac peptide, ventricular NP, has been found in selected species of teleost fish. However, in chicken, BNP is the primary cardiac peptide identified thus far. In contrast, the types of NP/s present in the reptilian heart are unknown, representing a considerable gap in our understanding of NP evolution. In the present study, we cloned and sequenced a BNP cDNA from the atria of representative species of reptile, including crocodile, lizard, snake, and tortoise. In addition, we cloned BNP from the pigeon atria. The reptilian and pigeon BNP cDNAs had ATTTA repeats in the 3' untranslated region, as observed in all vertebrate BNP mRNAs. A high sequence homology was evident when comparing reptile and pigeon preproBNP with the previously identified chicken preproBNP. In particular, the predicted mature BNP-29 was identical between crocodile, tortoise, and chicken, with pigeon having a single amino acid substitution; lizard and snake BNP had seven and nine substitutions, respectively. Furthermore, an ANP cDNA could only be cloned from the tortoise atria. Since ANP was not isolated from the heart of any non-chelonian reptile and appears to be absent in birds, we propose that the ANP gene has been lost after branching of the turtles in the amniote line. This data provides new avenues for research on NP function in reptiles.

  20. Deglutition induced atrial tachycardia and atrial fibrillation.

    PubMed

    Kanjwal, Yousuf; Imran, Naser; Grubb, Blair

    2007-12-01

    Deglutition induced supraventricular tachycardia is an uncommon condition postulated to be a vagally mediated phenomenon due to mechanical stimulation. Patients usually present with mild symptoms or may have severe debilitating symptoms. Treatment with Class I agents, beta blockers, calcium channel blockers, amiodarone and radiofrquency catheter ablation has shown to be successful in the majority of reported cases. We report the case of a 46-year-old healthy woman presenting with palpitations on swallowing that was documented to be transient atrial tachycardia with aberrant ventricular conduction as well as transient atrial fibrillation. She was successfully treated with propafenone with no induction of swallowing-induced tachycardia after treatment. This is also the first case to show swallowing-induced atrial tachycardia and atrial fibrillation in the same patient.

  1. Organized Atrial Tachycardias after Atrial Fibrillation Ablation

    PubMed Central

    Castrejón-Castrejón, Sergio; Ortega, Marta; Pérez-Silva, Armando; Doiny, David; Estrada, Alejandro; Filgueiras, David; López-Sendón, José L.; Merino, José L.

    2011-01-01

    The efficacy of catheter-based ablation techniques to treat atrial fibrillation is limited not only by recurrences of this arrhythmia but also, and not less importantly, by new-onset organized atrial tachycardias. The incidence of such tachycardias depends on the type and duration of the baseline atrial fibrillation and specially on the ablation technique which was used during the index procedure. It has been repeatedly reported that the more extensive the left atrial surface ablated, the higher the incidence of organized atrial tachycardias. The exact origin of the pathologic substrate of these trachycardias is not fully understood and may result from the interaction between preexistent regions with abnormal electrical properties and the new ones resultant from radiofrequency delivery. From a clinical point of view these atrial tachycardias tend to remit after a variable time but in some cases are responsible for significant symptoms. A precise knowledge of the most frequent types of these arrhythmias, of their mechanisms and components is necessary for a thorough electrophysiologic characterization if a new ablation procedure is required. PMID:21941669

  2. The use of pre-operative brain natriuretic peptides as a predictor of adverse outcomes after cardiac surgery: a systematic review and meta-analysis.

    PubMed

    Litton, Edward; Ho, Kwok M

    2012-03-01

    The objective of this systematic review was to assess whether pre-operative brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) are independent predictors of adverse outcomes after cardiac surgery. MEDLINE, Embase and the Cochrane Controlled Trials Register databases were searched. Eligible studies included observational or randomized control trials measuring natriuretic peptide concentrations before induction of anaesthesia for cardiac surgery. Two investigators independently extracted the data and assessed the validity of the included studies. The predictive ability of pre-operative BNP or NT pro-BNP on mortality, post-operative atrial fibrillation (AF) and intra-aortic balloon pump (IABP) requirement was meta-analysed. The association between BNP or NT pro-BNP and other outcomes was systematically summarized. A total of 4933 patients from 22 studies were considered in the systematic review. Ten studies with one or more outcomes of interest were included in the meta-analyses. The strength of association between pre-operative natriuretic peptide levels and adverse outcomes after surgery was variable, as was the size and quality of the included studies. The summary areas under the receiver operating characteristic curve for mortality, post-operative AF and post-operative IABP requirement were 0.61 (95% confidence interval [CI] 0.51-0.70), 0.61 (95% CI 0.58-0.64) and 0.81 (95% CI 0.73-0.89), respectively. With the limited data available, the associations between pre-operative natriuretic peptide levels and adverse outcomes after cardiac surgery were moderate. Future studies should assess whether pre-operative natriuretic peptides can provide additional independent predictive information to well-validated prognostic scores of cardiac surgery.

  3. Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

    PubMed

    Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

    2007-10-01

    In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

  4. Atrial fibrillation - discharge

    MedlinePlus

    Auricular fibrillation - discharge; A-fib - discharge; AF - discharge; Afib - discharge ... been in the hospital because you have atrial fibrillation . This condition occurs when your heart beats faster ...

  5. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability.

    PubMed

    Jacob, Matthias; Saller, Thomas; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Becker, Bernhard F

    2013-05-01

    Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations. This study investigates the impact and mechanism of action of physiological doses of ANP and related peptides on the vascular barrier. In isolated guinea pig hearts, prepared and perfused in a modified Langendorff mode with and without the intravascular presence of the colloid hydroxyethyl starch (HES), we measured functional changes in vascular permeability and glycocalyx shedding related to intracoronary infusion of physiological concentrations of A-, B- and C-type natriuretic peptide (ANP, BNP and CNP). Significant coronary venous washout of glycocalyx constituents (syndecan-1 and heparan sulfate) was observed. As tested for ANP, this effect was positively related to the intracoronary concentration. Intravascular shedding of the glycocalyx was morphologically confirmed by electron microscopy. Also, functional vascular barrier competence decreased, as indicated by significant increases in transudate formation and HES extravasation. Ortho-phenanthroline, a non-specific inhibitor of matrix metalloproteases, was able to reduce ANP-induced glycocalyx shedding. These findings suggest participation of natriuretic peptides in pathophysiological processes like heart failure, inflammation or sepsis. Inhibition of metalloproteases might serve as a basis for future therapeutical options.

  6. Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

    PubMed Central

    Pandey, Kailash N.

    2015-01-01

    The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed. PMID:26151885

  7. Plant natriuretic peptides: systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts.

    PubMed

    Gehring, Chris; Irving, Helen

    2013-06-01

    Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3',5'-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apoptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs.

  8. B and C types natriuretic peptides modify norepinephrine uptake and release in the rat adrenal medulla.

    PubMed

    Vatta, M S; Presas, M F; Bianciotti, L G; Rodriguez-Fermepin, M; Ambros, R; Fernandez, B E

    1997-01-01

    We have previously reported that atrial natriuretic factor (ANF) modulates adrenomedullar norepinephrine (NE) metabolism. On this basis, the aim of the present work was to study the effects of B and C types natriuretic peptides (BNP and CNP) on the uptake, intracellular distribution and release of 3H-NE. Experiments were carried out in rat adrenal medulla slices incubated "in vitro." Results showed that 100 nM of both, CNP and BNP, enhanced total and neuronal NE uptake. Both peptides (100 nM) caused a rapid increase in NE uptake during the first minute, which was sustained for 60 min. NE intracellular distribution was only modified by CNP (100 nM), which increased the granular fraction and decreased the cytosolic pool. On the other hand, spontaneous as well as evoked (KCl) NE release, was decreased by BNP and CNP (50 and 100 nM for spontaneous release and 1, 10, 50 and 100 nM for evoked output). The present results suggest that BNP and CNP may regulate catecholamine secretion and modulate adrenomedullary biological actions mediated by catecholamines, such as blood arterial pressure, smooth muscle tone, and metabolic activities.

  9. The Functional Genomics of Guanylyl Cyclase/Natriuretic Peptide Receptor-A: Perspectives and Paradigms

    PubMed Central

    Pandey, Kailash N.

    2011-01-01

    Cardiac hormones atrial and brain natriuretic peptides (ANP and BNP) activate guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) and produce the second messenger cGMP. The GC-A/NPRA is a member of the growing family of GC receptors. The recent biochemical, molecular, and genomic studies of GC-A/NPRA have provided important insights into the regulation and functional activity of this receptor protein with a particular emphasis on cardiac and renal protective roles in hypertension and cardiovascular disease states. The progress in this field of research has significantly strengthened and advanced our knowledge about the critical roles of Npr1 gene (coding for GC-A/NPRA) in control of fluid volume, blood pressure, cardiac remodeling, and other physiological functions and pathological states. Overall, this review attempts to provide insight and to delineate the current concepts in the field of functional genomics and signaling of GC-A/NPRA in hypertension and cardiovascular disease states at the molecular level. PMID:21375691

  10. Associates of an Elevated Natriuretic Peptide Level in Stable Heart Failure Patients: Implications for Targeted Management

    PubMed Central

    Dawkins, Ian; Murphy, Niamh; Collier, Patrick; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris J.

    2013-01-01

    Background. Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. Methods. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e′) was measured. Results. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e′, creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e′ and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Conclusion. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population. PMID:24453873

  11. Weight Loss, Saline Loading, and the Natriuretic Peptide System

    PubMed Central

    Arora, Pankaj; Reingold, Jason; Baggish, Aaron; Guanaga, Derek P.; Wu, Connie; Ghorbani, Anahita; Song, Yanna; Chen‐Tournaux, Annabel; Khan, Abigail May; Tainsh, Laurel T.; Buys, Emmanuel S.; Williams, Jonathan S.; Heublein, Denise M.; Burnett, John C.; Semigran, Marc J.; Bloch, Kenneth D.; Scherrer‐Crosbie, Marielle; Newton‐Cheh, Christopher; Kaplan, Lee M.; Wang, Thomas J.

    2015-01-01

    Background In epidemiologic studies, obesity has been associated with reduced natriuretic peptide (NP) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading. Methods and Results We enrolled 15 obese individuals (mean BMI 45±5.4 kg/m2) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large‐volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre‐operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6‐month visit, N‐terminal pro‐atrial NP (Nt‐proANP) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre‐operative visit (P<0.001). The rise in Nt‐pro‐ANP induced by the saline infusion (≈50%) was similar both before and after surgery (saline, P<0.001; interaction, P=0.2). Similar results were obtained for BNP and Nt‐proBNP; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure (P=0.004) and heart rate (P<0.001), and an increase in mitral annular diastolic velocity (P=0.02). Conclusion In obese individuals, weight loss is associated with a substantial increase in the “setpoint” of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss. PMID:25595796

  12. Brain natriuretic peptide predicts functional outcome in ischemic stroke

    PubMed Central

    Rost, Natalia S; Biffi, Alessandro; Cloonan, Lisa; Chorba, John; Kelly, Peter; Greer, David; Ellinor, Patrick; Furie, Karen L

    2011-01-01

    Background Elevated serum levels of brain natriuretic peptide (BNP) have been associated with cardioembolic (CE) stroke and increased post-stroke mortality. We sought to determine whether BNP levels were associated with functional outcome after ischemic stroke. Methods We measured BNP in consecutive patients aged ≥18 years admitted to our Stroke Unit between 2002–2005. BNP quintiles were used for analysis. Stroke subtypes were assigned using TOAST criteria. Outcomes were measured as 6-month modified Rankin Scale score (“good outcome” = 0–2 vs. “poor”) as well as mortality. Multivariate logistic regression was used to assess association between the quintiles of BNP and outcomes. Predictive performance of BNP as compared to clinical model alone was assessed by comparing ROC curves. Results Of 569 ischemic stroke patients, 46% were female; mean age was 67.9 ± 15 years. In age- and gender-adjusted analysis, elevated BNP was associated with lower ejection fraction (p<0.0001) and left atrial dilatation (p<0.001). In multivariate analysis, elevated BNP decreased the odds of good functional outcome (OR 0.64, 95%CI 0.41–0.98) and increased the odds of death (OR 1.75, 95%CI 1.36–2.24) in these patients. Addition of BNP to multivariate models increased their predictive performance for functional outcome (p=0.013) and mortality (p<0.03) after CE stroke. Conclusions Serum BNP levels are strongly associated with CE stroke and functional outcome at 6 months after ischemic stroke. Inclusion of BNP improved prediction of mortality in patients with CE stroke. PMID:22116811

  13. Morphological and morphometric study of atrial specific granules and other secretory components in dogs experimentally infected with Trypanosoma cruzi.

    PubMed Central

    Caliari, M. V.; Lana, M.; Leite, V. H.; Tafuri, W. L.

    1995-01-01

    Changes in blood volume can induce morphometric and morphological alterations in the secretory complex of the myoendocrine cells due to the stretching of atrial walls. These alterations were studied by electron microscopy, using dogs infected intraperitonially with Trypanosoma cruzi and necropsied during the acute phase of the infection when congestive heart failure was present. Several changes were observed in the myoendocrine cells of the heart: hypertrophy and hyperplasia of rough endoplasmic reticulum and Golgi complex, increase in telenuclear secretory complex, increase in fusion of type B atrial specific granules (ASG), decrease of the total number of ASG, enlargement of the maximum diameter of type A ASG and a relative increase in the number of type B ASG. These alterations suggest a larger secretory activity of the atrial myoendocrine cells with a larger secretion of atrial natriuretic peptide (ANP). Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7547444

  14. Angiotensin II down-regulates natriuretic peptide receptor-A expression and guanylyl cyclase activity in H9c2 (2-1) cardiac myoblast cells: Role of ROS and NF-κB.

    PubMed

    Gopi, Venkatachalam; Subramanian, Vimala; Manivasagam, Senthamizharasi; Vellaichamy, Elangovan

    2015-11-01

    Atrial natriuretic peptide (ANP)/natriuretic peptide receptor-A (NPR-A) system is suggested as an endogenous anti-hypertrophic protective mechanism of the heart. We have shown previously that Angiotensin II (ANG II), an effector molecule of renin-angiotensin-aldosterone system, down-regulates NPR-A expression and its activity in vivo rat heart. However, the underlying mechanism by which ANG II down-regulates NPR-A expression in the heart is not well understood. Hence, the present investigation was aimed to determine whether ANG II-stimulated reactive oxygen species (ROS) and NF-κB are involved in the down-regulation of NPR-A activity in H9c2 (2-1) cardiac myoblast cells. The H9c2 (2-1) cardiac myoblast cells were exposed to ANG II (10(-7) M for 20 h) with/or without blocker treatment (losartan-10 µM, N-acetyl cysteine (NAC)-10 mM and pyrrolidine dithiocarbamate (PDTC)-100 µM). On exposure, ANG II induced a significant decrease (P < 0.001) in the expression of Npr1 (coding for NPR-A) gene and NPR-A receptor-dependent guanylyl cyclase (GC) activity. The level of expression of proto-oncogenes (c-fos, c-myc, and c-jun) and natriuretic peptides (ANP and BNP) was increased in ANG II-treated cells when compared with control cells. Interestingly, ANG II-dependent repression of Npr1 gene expression and guanylyl cyclase (GC) activity was completely restored on treatment with losartan, while only a partial reversal was observed in NAC- and PDTC-co-treated cells. In conclusion, the results of this study suggest that ROS-mediated NF-κB activation mechanism is critically involved in the ANG II-mediated down-regulation of NPR-A expression and its GC activity.

  15. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients.

    PubMed

    Zoccali, C; Mallamaci, F; Benedetto, F A; Tripepi, G; Parlongo, S; Cataliotti, A; Cutrupi, S; Giacone, G; Bellanuova, I; Cottini, E; Malatino, L S

    2001-07-01

    This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.

  16. Atrial Tachycardias Following Atrial Fibrillation Ablation

    PubMed Central

    Sághy, László; Tutuianu, Cristina; Szilágyi, Judith

    2015-01-01

    One of the most important proarrhythmic complications after left atrial (LA) ablation is regular atrial tachycardia (AT) or flutter. Those tachycardias that occur after atrial fibrillation (AF) ablation can cause even more severe symptoms than those from the original arrhythmia prior to the index ablation procedure since they are often incessant and associated with rapid ventricular response. Depending on the method and extent of LA ablation and on the electrophysiological properties of underlying LA substrate, the reported incidence of late ATs is variable. To establish the exact mechanism of these tachycardias can be difficult and controversial but correlates with the ablation technique and in the vast majority of cases the mechanism is reentry related to gaps in prior ablation lines. When tachycardias occur, conservative therapy usually is not effective, radiofrequency ablation procedure is mostly successful, but can be challenging, and requires a complex approach. PMID:25308808

  17. Total plasma proANP increases with atrial dilatation in horses.

    PubMed

    Van Der Vekens, N; Hunter, I; Timm, A; Decloedt, A; De Clercq, D; Deprez, P; Goetze, J P; van Loon, G

    2015-12-19

    Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (P<0.001) higher in horses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; P<0.001) or horses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

  18. C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling.

    PubMed

    Rose, R A; Hatano, N; Ohya, S; Imaizumi, Y; Giles, W R

    2007-04-01

    In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts.

  19. Electrophysiological Mechanisms of Atrial Flutter

    PubMed Central

    Tai, Ching- Tai; Chen, Shin-Ann

    2006-01-01

    Atrial flutter (AFL) is a common arrhythmia in clinical practice. Several experimental models such as tricuspid regurgitation model, tricuspid ring model, sterile pericarditis model and atrial crush injury model have provided important information about reentrant circuit and can test the effect of antiarrhythmic drugs. Human atrial flutter has typical and atypical forms. Typical atrial flutter rotates around tricuspid annulus and uses the crista terminalis and sometimes sinus venosa as the boundary. The IVC-tricuspid isthmus is a slow conduction zone and the target of radiofrequency ablation. Atypical atrial flutter may arise from the right or left atrium. Right atrial flutter includes upper loop reentry, free wall reentry and figure of eight reentry. Left atrial flutter includes mitral annular atrial flutter, pulmonary vein-related atrial flutter and left septal atrial flutter. Radiofrequency ablation of the isthmus between the boundaries can eliminate these arrhythmias. PMID:16943903

  20. B-type natriuretic peptide (BNP) and proBNP: role of emerging markers to guide therapy and determine prognosis in cardiovascular disorders.

    PubMed

    Godkar, Darshan; Bachu, Kalyan; Dave, Bijal; Niranjan, Selva; Khanna, Ashok

    2008-01-01

    Over the last decade, one group of neurohormonal markers, including atrial natriuretic peptide (ANP), N-terminal pro-ANP, B-type natriuretic peptide (BNP), and N-terminal proBNP, has generated much interest in the evaluation and management of heart failure and acute coronary syndrome. There has been so much literature on the subject, especially concerning BNP and proBNP, that it leaves us confused at times about what the literature has to say about these markers. In this article, we have made an honest attempt to examine all the available literature in relation to the impact of BNP and proBNP on cardiovascular disease and present it to the reader in an assimilated fashion.

  1. Role of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis of patients with chronic atrial fibrillation and rheumatic mitral valve disease.

    PubMed

    Zhang, Daoliang; Liu, Xu; Chen, Xiaoqing; Gu, Jun; Li, Feng; Zhang, Wei; Zheng, Yue

    2014-01-01

    Atrial remodeling is involved in atrial fibrillation (AF), and atrial fibrosis is an important marker of atrial remodeling. On the basis of our previous animal studies of the mitogen-activated protein kinases (MAPKs)/transforming growth factor β1 (TGF-β1)/tumor necrosis factor pathway in atrial fibrosis, we undertook investigation of this signaling pathway in atrial fibrosis of patients with chronic AF (CAF) and rheumatic mitral valve disease. Fifty-six rheumatic mitral valve disease patients were divided into CAF (course of AF >12 months) and sinus rhythm (SR) groups. Left atrial appendage tissue was collected during heart surgery, and pathological examination was done to evaluate atrial fibrosis. Protein and mRNA expression of TGF-β1, TRAF6 and connective tissue growth factor (CTGF) and protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1) were measured. Histological examination revealed that the severity of atrial fibrosis in CAF patients was significantly higher, mRNA and protein expression of TGF-β1, TRAF6 and CTGF in CAF were significantly increased, and the protein expression of phosphorylated MAPKs and TAK1 was significantly increased in CAF compared to SR patients. The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis of CAF patients, and TRAF6 may become a new target for the treatment of atrial fibrosis.

  2. Left Atrial Appendage Exclusion for Atrial Fibrillation

    PubMed Central

    Syed, Faisal F.; DeSimone, Christopher V.; Friedman, Paul A.; Asirvatham, Samuel J.

    2015-01-01

    SYNOPSIS Percutaneous left atrial appendage (LAA) closure is increasingly being used as a treatment strategy to prevent stroke in patients with atrial fibrillation (AF) who have contraindications to anticoagulants. A number of approaches and devices have been developed in the last few years, each with their own unique set of advantages and disadvantages. We review the published studies on surgical and percutaneous approaches to LAA closure; focusing on stroke mechanisms in AF, LAA structure and function relevant to stroke prevention, practical differences in procedural approach, and clinical considerations surrounding management. PMID:25443240

  3. Case report and literature review: surgical treatment of a right atrial metastatic melanoma from a previously resected "advanced" primary site with regional lymph nodes involvement.

    PubMed

    Parissis, Haralabos; Al-Alao, Bassel Suffian; Young, Vincent K

    2012-10-01

    Although melanoma of the right atrium is a rare cardiac tumor, melanoma in general has a high propensity to involve the heart. Unfortunately, however, when the tumor is involving the heart, widespread metastasis ensues and hence surgery becomes a questionable option. We report a case of a young female who presented with an advanced skin primary melanoma and regional lymph node involvement and a metastasis into the right atrium. Postoperatively tumor dissemination was controlled with adjuvant chemotherapy. A vigorous attempt aiming at tumor clearance followed by adjuvant multimodality therapy along with a tumor surveillance program may improve survival even in advanced cases.

  4. Natriuretic peptides in cetaceans: identification, molecular characterization and changes in plasma concentration after landing.

    PubMed

    Naka, Tadaomi; Katsumata, Etsuko; Sasaki, Kazuki; Minamino, Naoto; Yoshioka, Motoi; Takei, Yoshio

    2007-06-01

    Dolphins are aquatic animals free from gravity, and this may have imposed significant changes in their cardiovascular status and its hormonal regulation compared with terrestrial animals. This study molecularly characterized two major cardiovascular hormones, atrial and B-type natriuretic peptides (ANP and BNP) and measured their changes in dolphin plasma concentrations in relation to the cardiovascular status of the animal. We initially identified ANP and BNP in three species of dolphins (Lagenorhynchus obliquidens, Phocoenoides dalli and Tursiops truncatus). ANP precursors are highly conserved in most mammals, but dolphin BNP precursors were more variable. In molecular phylogenetic analyses, dolphin ANP and BNP precursors grouped with those of artiodactyls, particularly to the camel peptides. The chromatographic characterization of tissue and plasma molecular forms using specific radioimmunoassays showed that the predominant ANP and BNP in the atrium are prohormone and mature peptide, respectively, whereas mature ANP and BNP are circulating in the dolphin blood. A mass spectrometric analysis showed that atrial BNP consists of 26 amino acids, rather than the 32-amino-acid form detected in other mammals. Finally, changes in plasma ANP and BNP concentrations were examined in captive bottlenose dolphins (Tursiops truncatus) after their pool was drained. Plasma ANP and BNP concentrations did not change after landing, unlike terrestrial mammals. Plasma angiotensin II and cortisol concentrations did not change either, showing minor stress after landing. Since landed dolphins show a different cardiovascular status on land than terrestrial mammals, plasma ANP and BNP concentrations seem to reflect the cardiovascular status characteristic of dolphins.

  5. Transforming growth factor β1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A - role of δEF1.

    PubMed

    Sen, Anagha; Kumar, Prerna; Garg, Renu; Lindsey, Sarah H; Katakam, Prasad V G; Bloodworth, Meaghan; Pandey, Kailash N

    2016-05-01

    The objective of this study was to determine the role of transforming growth factor β1 (TGF-β1) in transcriptional regulation and function of the guanylyl cyclase A/natriuretic peptide receptor A gene (Npr1) and whether cross-talk exists between these two hormonal systems in target cells. After treatment of primary cultured rat thoracic aortic vascular smooth muscle cells and mouse mesangial cells with TGF-β1, the Npr1 promoter construct containing a δ-crystallin enhancer binding factor 1 (δEF1) site showed 85% reduction in luciferase activity in a time- and dose-dependent manner. TGF-β1 also significantly attenuated luciferase activity of the Npr1 promoter by 62%, and decreased atrial natriuretic peptide-mediated relaxation of mouse denuded aortic rings ex vivo. Treatment of cells with TGF-β1 increased the protein levels of δEF1 by 2.4-2.8-fold, and also significantly enhanced the phosphorylation of Smad 2/3, but markedly reduced Npr1 mRNA and receptor protein levels. Over-expression of δEF1 showed a reduction in Npr1 promoter activity by 75%, while deletion or site-directed mutagenesis of δEF1 sites in the Npr1 promoter eliminated the TGF-β1-mediated repression of Npr1 transcription. TGF-β1 significantly increased the expression of α-smooth muscle actin and collagen type I α2 in rat thoracic aortic vascular smooth muscle cells, which was markedly attenuated by atrial natriuretic peptide in cells over-expressing natriuretic peptide receptor A. Together, the present results suggest that an antagonistic cascade exists between the TGF-β1/Smad/δEF1 pathways and Npr1 expression and receptor signaling that is relevant to renal and vascular remodeling, and may be critical in the regulation of blood pressure and cardiovascular homeostasis. © 2016 Federation of European Biochemical Societies.

  6. Natriuretic peptide-guided management in heart failure.

    PubMed

    Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

    2016-08-01

    Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

  7. Surgery for Atrial Fibrillation.

    PubMed

    Lawrance, Christopher P; Henn, Matthew C; Damiano, Ralph J

    2016-04-01

    Atrial fibrillation is the most common cardiac arrhythmia, and its treatment options include drug therapy or catheter-based or surgical interventions. The surgical treatment of atrial fibrillation has undergone multiple evolutions over the last several decades. The Cox-Maze procedure went on to become the gold standard for the surgical treatment of atrial fibrillation and is currently in its fourth iteration (Cox-Maze IV). This article reviews the indications and preoperative planning for performing a Cox-Maze IV procedure. This article also reviews the literature describing the surgical results for both approaches including comparisons of the Cox-Maze IV to the previous cut-and-sew method.

  8. Surgery for atrial fibrillation.

    PubMed

    Lawrance, Christopher P; Henn, Matthew C; Damiano, Ralph J

    2014-11-01

    Atrial fibrillation is the most common cardiac arrhythmia, and its treatment options include drug therapy or catheter-based or surgical interventions. The surgical treatment of atrial fibrillation has undergone multiple evolutions over the last several decades. The Cox-Maze procedure went on to become the gold standard for the surgical treatment of atrial fibrillation and is currently in its fourth iteration (Cox-Maze IV). This article reviews the indications and preoperative planning for performing a Cox-Maze IV procedure. This article also reviews the literature describing the surgical results for both approaches including comparisons of the Cox-Maze IV to the previous cut-and-sew method.

  9. Natriuretic peptide type C induces sperm attraction for fertilization in mouse

    PubMed Central

    Kong, Nana; Xu, Xiaoting; Zhang, Yu; Wang, Yakun; Hao, Xiaoqiong; Zhao, Yu; Qiao, Jie; Xia, Guoliang; Zhang, Meijia

    2017-01-01

    Mammalian spermatozoa undergo selective movement along the isthmus of the oviduct to the ampulla during ovulation, which is a prerequisite for fertilization. The factor(s) that involves in selective spermatozoa movement is still unknown. In this study, we found that the oviductal epithelium in mouse ampulla expressed high levels of natriuretic peptide type C (NPPC) in the presence of ovulated oocyte-cumulus complexes (OCCs). Spermatozoa expressed NPPC receptor natriuretic peptide receptor 2 (NPR2, a guanylyl cyclase) on the midpiece of flagellum. NPPC increased intracellular levels of cGMP and Ca2+ of spermatozoa, and induced sperm accumulation in the capillary by attraction. Importantly, spermatozoa from Npr2 mutant mice were not attracted by NPPC, preventing fertilization in vivo. Oocyte-derived paracrine factors promoted the expression of Nppc mRNA in the ampulla. Therefore, NPPC secreted by oviductal ampulla attracts spermatozoa towards oocytes, which is essential for fertilization. PMID:28054671

  10. Left Atrial Ablation for Atrial Fibrillation

    PubMed Central

    Sternik, Leonid; Schaff, Hartzel V.; Luria, David; Glikson, Michael; Kogan, Alexander; Malachy, Ateret; First, Maya; Raanani, Ehud

    2011-01-01

    The maze procedure is the gold standard for the ablation of atrial fibrillation, and the “box lesion” around the pulmonary veins is the most important part of this procedure. We have created this lesion with a bipolar radiofrequency ablator, abandoning the usual use of this device (to achieve bilateral epicardial isolation of the pulmonary veins). From March 2004 through the end of May 2010, we performed surgical ablation of atrial fibrillation in 240 patients. Of this number, 205 underwent operation by a hybrid maze technique and the remaining 35 (our study cohort) underwent the creation of a box lesion around the pulmonary veins by means of a bipolar radiofrequency device. Ablation lines were created by connecting the left atriotomy to the amputated left atrial appendage, with 2 ablation lines made with a bipolar radiofrequency device above and below the pulmonary veins. Lesions were made along the transverse and oblique sinuses by epicardial and endocardial application of a bipolar device. The left atrial isthmus was ablated by bipolar radiofrequency and cryoprobe. No complications were associated with the box lesion: 90% and 89% of patients were in sinus rhythm at 3 and 6 months of follow-up, respectively. By creating a box lesion around the pulmonary veins, we expect to improve transmurality by means of epicardial and endocardial ablation of 1 rather than 2 layers of atrial wall, as in epicardial pulmonary vein isolation. Isolation of the entire posterior wall of the left atrium is better electrophysiologically and renders dissection around the pulmonary veins unnecessary. PMID:21494518

  11. Influence of regular physical activity and caloric restriction on β-adrenergic and natriuretic peptide receptor expression in retroperitoneal adipose tissue of OLETF rats.

    PubMed

    Jenkins, Nathan T; Padilla, Jaume; Rector, R Scott; Laughlin, M Harold

    2013-11-01

    The mechanisms underlying exercise-induced increases in adipose tissue blood flow and lipolysis involve both β-adrenergic receptor (βAR)- and natriuretic peptide receptor (NPR)-dependent processes. We hypothesized that daily wheel running (RUN) would increase the expression of NPR1, NPR2, βAR2 and βAR3 in retroperitoneal (RP) and epididymal (EPI) adipose tissues of obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Four-week-old OLETF rats were assigned to sedentary (SED, n = 6), calorie-restricted (CR, n = 8; fed 70% of SED) or RUN groups (n = 8). Rats were killed at 40 weeks of age. By design, body weight and adiposity were similar between RUN and CR animals, but each was lower than SED (P < 0.01). Compared with SED, RP depots of RUN rats exhibited 1.7- to 3.2-fold greater NPR1, NPR2, βAR2 and βAR3 mRNA levels (all P < 0.05). There were no differences between CR and SED in the expression of these genes in RP adipose tissues, and there were no differences in gene expression among groups in EPI adipose tissues. At the protein level, βAR2 and βAR3 were elevated in RUN and CR groups relative to the SED group in RP adipose tissues. In order to gain insight into the mechanisms underlying the activity-induced increases in NPR and βAR mRNAs, RP adipose tissue explants from Wistar rats were treated with atrial natriuretic peptide (ANP), adrenaline and/or S-nitroso-N-acetyl-dl-penicillamine (SNAP; a nitric oxide donor) in organ culture experiments. SNAP synergistically enhanced adrenaline- and ANP-stimulated increases in NPR2 and βAR2 mRNA levels. Our data suggest that physical activity-induced increases in nitric oxide interact with adrenaline and ANP to trigger the induction of NPR and βAR mRNAs in the RP adipose tissue depot of the OLETF rat.

  12. Atrial fibrillation and gastroesophageal reflux disease: From the cardiologist perspective.

    PubMed

    Floria, Mariana; Drug, Vasile Liviu

    2015-03-14

    We have read with interest the paper by Roman C. and colleagues discussing the relationship between gastroesophageal reflux disease and atrial fibrillation. The review is presenting the available evidence for the common pathogenic mechanisms. However, from a cardiologist perspective, some available data were not highlighted in the review, cardiovascular involvement in gastroesophageal reflux is less assessed. Hypertension, obesity or diabetes mellitus are substrate for left atrial remodeling that initiate and sustained atrial fibrillation development. One of the pathophysiologic mechanisms in atrial fibrillation is the presence of a trigger. Gastroesophageal reflux could be only a trigger for this arrhythmia. We believe that atrial fibrillation should be considered as possible extraesophageal syndrome in the gastroesophageal reflux classification.

  13. Atrial Fibrillation in Children

    MedlinePlus

    ... attribute childhood AF to congenital heart abnormalities or post-surgical complications. Learn more about children and arrhythmia. This content was last reviewed July 2016. Atrial Fibrillation • Introduction • What is ...

  14. Atrial Fibrillation Medications

    MedlinePlus

    ... think you are pregnant If you notice red, dark brown or black urine or stools If you ... Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • Understand your Risk for AFib Children • Symptoms of ...

  15. Atrial Fibrillation - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/atrialfibrillation.html Other topics A-Z Expand Section ...

  16. Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?

    PubMed

    Sidorova, Tatiana N; Mace, Lisa C; Wells, K Sam; Yermalitskaya, Liudmila V; Su, Pei-Fang; Shyr, Yu; Atkinson, James B; Fogo, Agnes B; Prinsen, Joseph K; Byrne, John G; Petracek, Michael R; Greelish, James P; Hoff, Steven J; Ball, Stephen K; Glabe, Charles G; Brown, Nancy J; Barnett, Joey V; Murray, Katherine T

    2014-12-02

    Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated. Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for PAOs using a conformation-specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium-specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement/repair (n=24). Immunostaining detected intracellular PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Hypertension Is Associated With Preamyloid Oligomers in Human Atrium: A Missing Link in Atrial Pathophysiology?

    PubMed Central

    Sidorova, Tatiana N.; Mace, Lisa C.; Wells, K. Sam; Yermalitskaya, Liudmila V.; Su, Pei‐Fang; Shyr, Yu; Atkinson, James B.; Fogo, Agnes B.; Prinsen, Joseph K.; Byrne, John G.; Petracek, Michael R.; Greelish, James P.; Hoff, Steven J.; Ball, Stephen K.; Glabe, Charles G.; Brown, Nancy J.; Barnett, Joey V.; Murray, Katherine T.

    2014-01-01

    Background Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ‐specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated. Methods and Results Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for PAOs using a conformation‐specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium‐specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement/repair (n=24). Immunostaining detected intracellular PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. Conclusion PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension. PMID:25468655

  18. Atrial fibrillation (acute onset)

    PubMed Central

    2014-01-01

    Introduction Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil. PMID:25430048

  19. Can Atrial Fibrillation Be Prevented?

    MedlinePlus

    ... from the NHLBI on Twitter. How Can Atrial Fibrillation Be Prevented? Following a healthy lifestyle and taking ... for heart disease may help you prevent atrial fibrillation (AF). These steps include: Following a heart healthy ...

  20. Biomarkers in atrial fibrillation: a clinical review.

    PubMed

    Hijazi, Ziad; Oldgren, Jonas; Siegbahn, Agneta; Granger, Christopher B; Wallentin, Lars

    2013-05-01

    Assessment of atrial fibrillation (AF)-associated stroke risk is at present mainly based on clinical risk scores such as CHADS2 and CHA2DS2-VASc, although these scores provide only modest discrimination of risk for individual patients. Biomarkers derived from the blood may help refine risk assessment in AF for stroke outcomes and for mortality. Recent studies of biomarkers in AF have shown that they can substantially improve risk stratification. Cardiac biomarkers, such as troponin and natriuretic peptides, significantly improve risk stratification in addition to current clinical risk stratification models. Similar findings have recently been described for markers of renal function, coagulation, and inflammation in AF populations based on large randomized prospective clinical trials or large community-based cohorts. These new findings may enable development of novel tools to improve clinical risk assessment in AF. Biomarkers in AF may also improve the understanding of the pathophysiology of AF further as well as potentially elucidate novel treatment targets. This review will highlight novel associations of biomarkers and outcomes in AF as well as recent progress in the use of biomarkers for risk stratification.

  1. Methods for the development and assessment of atrial fibrillation and heart failure dog models

    PubMed Central

    Urban, Jon F; Gerhart, Renee L; Krzeszak, Jason R; Leet, Corey R; Lentz, Linnea R; McClay, Carolyn B

    2011-01-01

    Objective To report Medtronic experiences with the development of animal models for atrial fibrillation (AF) and chronic heart failure (CHF) using high-rate pacing for AF and microemboli for CHF. Methods For the AF model, an atrial lead was attached to a Medtronic Synergy™ neurostimulator, which was programmed to stimulate at 50 Hz in an on-off duty cycle. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and N-terminal pro brain natriuretic peptide (NT-proBNP) were assayed at select time points. For CHF model, a serial injection of 90 µm polystyrene microspheres at 62,400 beads/mL (Polybead, Polysciences, Inc.) was performed to induce global ischemia, either with weekly monitoring and embolization schedule (group 1, n = 25) or with biweekly monitoring and emboliation schedule (group 2, n = 36 ). Echocardiograms were used along with ventriculograms and magnetic resonance imaging scans weekly to assess cardiac function and ANP, BNP and NT-proBNP were monitored. Results For the AF model, the days to sustained AF for four animals following surgery were 7, 25, 21 and 19, respectively; For the CHF model, the days to meet CHF endpoints were 116 in group 1 and 89 in group 2. For both AF and CHF models, NT-proBNP correlated well with the development of disease states. Conclusion Our experience for the development and assessment of AF and CHF dog models may help researchers who are in search for animal model for assessing the safety and efficacy of a device-based therapy. PMID:22783299

  2. Recent advances in the molecular pathophysiology of atrial fibrillation

    PubMed Central

    Wakili, Reza; Voigt, Niels; Kääb, Stefan; Dobrev, Dobromir; Nattel, Stanley

    2011-01-01

    Atrial fibrillation (AF) is an extremely common cardiac rhythm disorder that causes substantial morbidity and contributes to mortality. The mechanisms underlying AF are complex, involving both increased spontaneous ectopic firing of atrial cells and impulse reentry through atrial tissue. Over the past ten years, there has been enormous progress in understanding the underlying molecular pathobiology. This article reviews the basic mechanisms and molecular processes causing AF. We discuss the ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia. We conclude with a discussion of the potential therapeutic implications that might arise from an improved mechanistic understanding. PMID:21804195

  3. Continuous intra- and postoperative thoracic epidural analgesia attenuates brain natriuretic peptide release after major abdominal surgery.

    PubMed

    Suttner, Stefan; Lang, Katrin; Piper, Swen N; Schultz, Harald; Röhm, Kerstin D; Boldt, Joachim

    2005-09-01

    We investigated whether blocking afferent nociceptive inputs by continuous intra- and postoperative thoracic epidural analgesia (TEA) would decrease plasma concentrations of brain natriuretic peptide (BNP) in patients who were at risk for, or had, coronary artery disease. Twenty-eight patients undergoing major abdominal surgery received either general anesthesia supplemented with a continuous thoracic epidural infusion of 1.25 mg/mL bupivacaine and 1 microg/mL sufentanil (n = 14; TEA) or general anesthesia followed by IV patient-controlled analgesia (n = 14; IV PCA). Visual analog scale pain scores, hemodynamics, plasma catecholamines, cardiac troponin T, atrial natriuretic peptide (ANP), and BNP were serially measured preoperatively, 90 min after skin incision, at arrival in the intensive care unit, and in the morning of the first, second, and third postoperative day. Dynamic visual analog scale scores were significantly less in the TEA group. TEA reduced the postoperative heart rate without affecting other hemodynamic variables. Plasma epinephrine increased perioperatively in both groups but was significantly lower in the TEA group. Baseline ANP and BNP concentrations were similar between groups (TEA 3.4 +/- 1.8 and 27.0 +/- 12.3 pg/mL; IV PCA 3.1 +/- 2.0 and 25.9 +/- 13.0 pg/mL, respectively). ANP and BNP increased perioperatively in both groups, with significantly lower postoperative BNP levels in TEA patients (TEA 92.1 +/- 31.9 pg/mL; IV PCA 161.2 +/- 44.7 pg/mL). No such difference was observed in plasma ANP concentrations. Plasma cardiac troponin T concentrations were within normal limits in both groups at all times. We conclude that continuous perioperative TEA using local anesthetics and opioids attenuated the release of BNP in patients undergoing major abdominal surgery who were at risk for, or had, coronary artery disease.

  4. Atrial selectivity of antiarrhythmic drugs

    PubMed Central

    Ravens, Ursula; Poulet, Claire; Wettwer, Erich; Knaut, Michael

    2013-01-01

    New antiarrhythmic drugs for treatment of atrial fibrillation should ideally be atrial selective in order to avoid pro-arrhythmic effects in the ventricles. Currently recognized atrial selective targets include atrial Nav1.5 channels, Kv1.5 channels and constitutively active Kir3.1/3.4 channels, each of which confers atrial selectivity by different mechanisms. Na+ channel blockers with potential- and frequency-dependent action preferentially suppress atrial fibrillation because of the high excitation rate and less negative atrial resting potential, which promote drug binding in atria. Kv1.5 channels are truly atrial selective because they do not conduct repolarizing current IKur in ventricles. Constitutively active IK,ACh is predominantly observed in remodelled atria from patients in permanent atrial fibrillation (AF). A lot of effort has been invested to detect compounds which will selectively block Kir3.1/Kir3.4 in their remodelled constitutively active form. Novel drugs which have been and are being developed aim at atrial-selective targets. Vernakalant and ranolazine which mainly block atrial Na+ channels are clinically effective. Newly designed selective IKur blockers and IK,ACh blockers are effective in animal models; however, clinical benefit in converting AF into sinus rhythm (SR) or reducing AF burden remains to be demonstrated. In conclusion, atrial-selective antiarrhythmic agents have a lot of potential, but a long way to go. PMID:23732646

  5. Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

    PubMed

    Oliveira, Marcela Silva; Carmona, Fabio; Vicente, Walter V A; Manso, Paulo H; Mata, Karina M; Celes, Mara Rúbia; Campos, Erica C; Ramos, Simone G

    2017-04-01

    Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β1, β2-adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β1 and β2 receptors and

  6. Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease.

    PubMed

    Wang, Rui; Yi, Xin; Li, Xiaoyan; Jiang, Xuejun

    2015-01-01

    Fibroblast growth factor-21 (FGF-21) has been discovered as a strong hormone, plays an important role in lipid metabolism, glucose metabolism, associated with several diseases such as obesity, metabolic syndrome, diabetes mellitus, and cardiovascular events; however, no evidence is available concerning the relationship of FGF-21 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). Twenty-four rheumatic heart disease patients were divided into two groups, 12 cases with AF and 12 cases with sinus rhythm (SR). Clinical characteristics and blood samples were collected before surgery; right atrial appendage samples were taken in the surgery of valve replacement. HE staining was performed to determine cross-sectional area of atrial myocytes; Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to evaluate the degree of cardiac fibrosis; the level of FGF-21 was evaluated via enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and real-time polymerase chain reaction (PCR). Compared with SR group, cross-sectional area of atrial myocytes and collagen volume fraction were significantly increased in the atrial tissue of AF group. The distribution of FGF-21 in the AF group was remarkably higher than SR group. In addition, plasma and mRNA levels of FGF-21 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. Using linear correlation analysis, the expression level of FGF-21 was found to be positively related to the degree of atrial fibrosis. FGF-21 might involve in the development and maintenance of atrial fibrosis in atrial fibrillation with rheumatic heart disease, and FGF-21 could be used as a novel biomarker to evaluate myocardial fibrosis in the future.

  7. [Differences in atrial remodelling between right and left atria in patients with chronic atrial fibrillation].

    PubMed

    Tamargo Menéndez, Juan

    2011-01-01

    Atrial fibrillation starts in the left atrium and from there the activity invades the atrial tissues and causes an inhomogeneous shortening the duration of atrial action potential duration and refractoriness. The purpose of this study was to compare the voltage-dependent potassium currents in human cells isolated from the right and left atria and to determine whether electrical remodeling produced by chronic atrial fibrillation (CAF) differentially affects voltage-dependent potassium currents involved in atrial repolarization in each atrium as compared to sinus rhythm (SR). The currents were recorded using the whole-cell configuration of the patch-clamp technique. We found that in atrial cardiomyocytes of patients both in SR and in CAF there are three types of cells according to their main voltage-dependent repolarizing potassium current: the Ca(2+)-independent 4-aminopyridine sensitive component of the transient outward current (I(to1)) and the ultrarapid (I(Kur)), rapid (I(Kr)) and slow (I(Ks)) components of the delayed rectifier current. CAF differentially modified the proportion of these 3 types of cells on each atrium: CAF reduced the I(to1) more markedly in the left than in the right atria, while I(Kur) was more markedly reduced in the right than in the left atria. Interestingly, in both atria, CAF markedly increased the I(Ks). This increase was enhanced by isoproterenol and suppressed by atenolol. These changes produce a non-uniform shortening of atrial repolarization that facilitates the reentry of the cardiac impulse and the perpetuation of the arrhythmia.

  8. Endurance sport practice as a risk factor for atrial fibrillation and atrial flutter.

    PubMed

    Mont, Lluís; Elosua, Roberto; Brugada, Josep

    2009-01-01

    Although the benefits of regular exercise in controlling cardiovascular risk factors have been extensively proven, little is known about the long-term cardiovascular effects of regular and extreme endurance sport practice, such as jogging, cycling, rowing, swimming, etc. Recent data from a small series suggest a relationship between regular, long-term endurance sport practice and atrial fibrillation (AF) and flutter. Reported case control studies included less than 300 athletes, with mean age between 40 and 50. Most series recruited only male patients, or more than 70% males, who had been involved in intense training for many years. Endurance sport practice increases between 2 and 10 times the probability of suffering AF, after adjusting for other risk factors. The possible mechanisms explaining the association remain speculative. Atrial ectopic beats, inflammatory changes, and atrial size have been suggested. Some of the published studies found that atrial size was larger in athletes than in controls, and this was a predictor for AF. It has also been shown that the left atrium may be enlarged in as many as 20% of competitive athletes. Other proposed mechanisms are increased vagal tone and bradycardia, affecting the atrial refractory period; however, this may facilitate rather than cause the arrhythmia. In summary, recent data suggest an association between endurance sport practice and atrial fibrillation and flutter. The underlying mechanism explaining this association is unclear, although structural atrial changes (dilatation and fibrosis) are probably present. Larger longitudinal studies and mechanistic studies are needed to further characterize the association to clarify whether a threshold limit for the intensity and duration of physical activity may prevent AF, without limiting the cardiovascular benefits of exercise.

  9. Rivaroxaban in atrial fibrillation

    PubMed Central

    Giorgi, Mariano A; Miguel, Lucas San

    2012-01-01

    Warfarin is the traditional therapeutic option available to manage thromboembolic risk in atrial fibrillation. The hemorrhagic risk with warfarin depends mainly on the international normalized ratio (INR). Data from randomized controlled trials show that patients have a therapeutic INR (2.00–3.00) only 61%–68% of the time while taking warfarin, and this target is sometimes hard to establish. Many compounds have been developed in order to optimize the profile of oral anticoagulants. We focus on one of them, rivaroxaban, comparing it with novel alternatives, ie, dabigatran and apixaban. The indication for rivaroxaban in nonvalvular atrial fibrillation was evaluated in ROCKET-AF (Rivaroxaban-once daily, Oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation). In this trial, rivaroxaban was associated with a 12% reduction in the incidence of the primary endpoint compared with warfarin (hazard ratio 0.88; 95% confidence interval [CI] 0.74–1.03; P < 0.001 for noninferiority and P = 0.12 for superiority). However, patients remained in the therapeutic range for INR only 55% of the time, which is less than that in RE-LY (the Randomized Evaluation of Long-Term Anticoagulation Therapy, 64%) and in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, 66%). This shorter time spent in the therapeutic range has been one of the main criticisms of the ROCKET-AF trial, but could actually reflect what happens in real life. In addition, rivaroxaban exhibits good pharmacokinetic and pharmacoeconomic properties. Novel anticoagulants are a viable and commercially available alternative to vitamin K antagonists nowadays for the prevention of thromboembolic complications in atrial fibrillation. Rivaroxaban is an attractive alternative, but the true picture of this novel compound in atrial fibrillation will only become available with more widespread

  10. Right atrial spleen.

    PubMed Central

    Kuijer, P; Dion, R; van Merrienboer, F

    1985-01-01

    A large cardiac tumour occupying most of the right atrium and the right ventricle and causing inflow obstruction to the right heart was confirmed by cross sectional echocardiography in a 41 year old man. After surgical resection histological examination showed that the atrial tumour had the characteristics of splenic tissue. Possible mechanisms for the development of such a tumour include an origin analogous to that of an accessory spleen or the implantation and subsequent growth of lymphoid tissue in a pre-existing superior vena caval or high right atrial angioma. Images PMID:4041304

  11. Clathrin-dependent internalization, signaling, and metabolic processing of guanylyl cyclase/natriuretic peptide receptor-A.

    PubMed

    Somanna, Naveen K; Mani, Indra; Tripathi, Satyabha; Pandey, Kailash N

    2017-09-12

    Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using (125)I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells. Treatment of recombinant HEK-293 cells with ANP time-dependently accelerated the internalization of receptor from the cell surface to the cell interior. However, the internalization of ligand-receptor complexes of NPRA was drastically decreased by the specific inhibitors of clathrin- and dynamin-dependent receptor internalization, almost 85% by monodansylcadaverine, 80% by chlorpromazine, and 90% by mutant dynamin, which are specific blockers of endocytic vesicle formation. Visualizing the internalization of NPRA and enhanced GFP-tagged NPRA in HEK-293 cells by confocal microscopy demonstrated the formation of endocytic vesicles after 5 min of ANP treatment; this effect was blocked by the inhibitors of clathrin and by mutant dynamin construct. Our results suggest that NPRA undergoes internalization via clathrin-mediated endocytosis as part of its normal itinerary, including trafficking, signaling, and metabolic degradation.

  12. Subcellular trafficking of guanylyl cyclase/natriuretic peptide receptor-A with concurrent generation of intracellular cGMP.

    PubMed

    Mani, Indra; Garg, Renu; Tripathi, Satyabha; Pandey, Kailash N

    2015-09-15

    Atrial natriuretic peptide (ANP) activates guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), which lowers blood pressure and blood volume. The objective of the present study was to visualize internalization and trafficking of enhanced GFP (eGFP)-tagged NPRA (eGFP-NPRA) in human embryonic kidney-293 (HEK-293) cells, using immunofluorescence (IF) and co-immunoprecipitation (co-IP) of eGFP-NPRA. Treatment of cells with ANP initiated rapid internalization and co-localization of the receptor with early endosome antigen-1 (EEA-1), which was highest at 5 min and gradually decreased within 30 min. Similarly, co-localization of the receptor was observed with lysosome-associated membrane protein-1 (LAMP-1); however, after treatment with lysosomotropic agents, intracellular accumulation of the receptor gradually increased within 30 min. Co-IP assays confirmed that the localization of internalized receptors occurred with subcellular organelles during the endocytosis of NPRA. Rab 11, which was used as a recycling endosome (Re) marker, indicated that ∼20% of receptors recycled back to the plasma membrane. ANP-treated cells showed a marked increase in the IF of cGMP, whereas receptor was still trafficking into the intracellular compartments. Thus, after ligand binding, NPRA is rapidly internalized and trafficked from the cell surface into endosomes, Res and lysosomes, with concurrent generation of intracellular cGMP. © 2015 Authors.

  13. P Wave Morphology in Guiding the Ablation Strategy of Focal Atrial Tachycardias and Atrial Flutter

    PubMed Central

    Lee, Justin M. S; Fynn, Simon P

    2015-01-01

    Focal atrial tachycardias arise preferentially from specific locations within the atria. Careful analysis of the P wave can provide useful information about the chamber and likely site of origin within that chamber. Macro-reentrant atrial flutter also tends to occur over a limited number of potential circuits. In this case, the ECG usually gives a guide to the chamber of origin, but unless it shows a specific morphology it is less useful in delineating the circuit involved. Nonetheless, prior knowledge of the likely chamber of origin helps to plan the ablation strategy. PMID:25308814

  14. Association of Atrial Fibrillation with Morphological and Electrophysiological Changes of the Atrial Myocardium.

    PubMed

    Matějková, Adéla; Šteiner, Ivo

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. For long time it was considered as pure functional disorder, but in recent years, there were identified atrial locations, which are involved in the initiation and maintenance of this arrhythmia. These structural changes, so called remodelation, start at electric level and later they affect contractility and morphology. In this study we attempted to find a possible relation between morphological (scarring, amyloidosis, left atrial (LA) enlargement) and electrophysiological (ECG features) changes in patients with AF. We examined grossly and histologically 100 hearts of necropsy patients - 54 with a history of AF and 46 without AF. Premortem ECGs were evaluated. The patients with AF had significantly heavier heart, larger LA, more severely scarred myocardium of the LA and atrial septum, and more severe amyloidosis in both atria. Severity of amyloidosis was higher in LAs vs. right atria (RAs). Distribution of both fibrosis and amyloidosis was irregular. The most affected area was in the LA anterior wall. Patients with a history of AF and with most severe amyloidosis have more often abnormally long P waves. Finding of long P wave may contribute to diagnosis of a hitherto undisclosed atrial fibrillation.

  15. The role of natriuretic peptides in inflammation and immunity.

    PubMed

    Casserly, Brian P; Sears, Edmund H; Gartman, Eric J

    2010-06-01

    The natriuretic peptides (NPs) are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of effects throughout the body. There is growing realization that NP actions go far beyond volume and blood pressure homeostasis. Their pleiotropic effects include a significant role in regulating the immune system. Localization of NP receptors in various immune organs as well as in modulation of inflammation in vascular disease supports this hypothesis. Immune cells, including macrophages, dendritic cells, and T lymphocytes, express receptors for NPs. NPs are also involved in polarizing the immune response to allergens. NPs play an important role in shaping the early immune response to environmental antigens and appear to play a critical role in the interaction between cells of the innate and adaptive immune systems. The recent explosion of basic and clinical research has resulted in improved understanding of their molecular structure. This has facilitated development of chimeric forms of NPs as well as more convenient routes of administration. Thus, the NPs and their receptors could be exploited to develop therapeutics for the inflammatory and immune responses in wide range of diseases. Also discussed are several patents regarding NPs in the present review.

  16. Diuretic and natriuretic activity of two mistletoe species in rats

    PubMed Central

    Jadhav, Namita; Patil, C. R.; Chaudhari, K. B.; Wagh, J. P.; Surana, S. J.; Jadhav, R. B.

    2010-01-01

    In different cultural groups, the hemiparasitic plants of the families Loranthaceae and Viscaceae (mistletoes) are frequently used in the treatment of hypertension and/or as diuretic agents. However, it remains unclear as to what commonality makes them diuretic agents or a remedy for hypertension. In this article, the diuretic activity of methanol extracts of Viscum articulatum (VA) Burm. f. and Helicanthus elastica (HE) (Ders.) Dans. in rats is reported. The extracts were administered orally at doses of 100, 200 and 400 mg/kg to rats that had been fasted and deprived of water for 18 hours. Investigations were carried out for diuretic, saluretic and natriuretic effects. The polyphenolic and triterpenoid contents were determined quantitatively using chemical assays and high performance liquid chromatography (HPLC) analysis, respectively. The extracts of VA and HE demonstrated significant and dose-dependent diuretic activity in rats. It was found that while VA mimics the furosemide pattern, HE demonstrated a dose-dependent increase in diuresis, along with an increase in potassium-sparing effects. Phytochemical analysis revealed that polyphenolics and triterpenoids, such as oleanolic acid and lupeol, are the major phytochemicals involved. It was also found that in different combinations, these phytochemicals differed in the way they influenced the electrolyte excretion. A higher content of polyphenolics in association with lower triterpenoid content was found to favor potassium-sparing effects. PMID:21808540

  17. Atrial and ventricular tachyarrhythmias in military personnel.

    PubMed

    Posselt, Bonnie N; Cox, A T; D'Arcy, J; Rooms, M; Saba, M

    2015-09-01

    Although rare, sudden cardiac death does occur in British military personnel. In the majority of cases, the cause is considered to be a malignant ventricular tachyarrhythmia, which can be precipitated by a number of underlying pathologies. Conversely, a tachyarrhythmia may have a more benign and treatable cause, yet the initial clinical symptoms may be similar, making differentiation difficult. This is an overview of the mechanisms underlying the initiation and propagation of arrhythmias and the various pathological conditions that predispose to arrhythmia genesis, classified according to which parts of the heart are involved: atrial tachyarrhythmias, atrial and ventricular, as well as those affecting the ventricles alone. It encompasses atrial tachycardia, atrial flutter, supraventricular tachycardias and ventricular tachycardias, including the more commonly encountered inherited primary electrical diseases, also known as the channelopathies. The clinical features, investigation and management strategies are outlined. The occupational impact-in serving military personnel and potential recruits-is described, with explanations relating to the different conditions and their specific implication on continued military service.

  18. Exploiting periodicity to extract the atrial activity in atrial arrhythmias

    NASA Astrophysics Data System (ADS)

    Llinares, Raul; Igual, Jorge

    2011-12-01

    Atrial fibrillation disorders are one of the main arrhythmias of the elderly. The atrial and ventricular activities are decoupled during an atrial fibrillation episode, and very rapid and irregular waves replace the usual atrial P-wave in a normal sinus rhythm electrocardiogram (ECG). The estimation of these wavelets is a must for clinical analysis. We propose a new approach to this problem focused on the quasiperiodicity of these wavelets. Atrial activity is characterized by a main atrial rhythm in the interval 3-12 Hz. It enables us to establish the problem as the separation of the original sources from the instantaneous linear combination of them recorded in the ECG or the extraction of only the atrial component exploiting the quasiperiodic feature of the atrial signal. This methodology implies the previous estimation of such main atrial period. We present two algorithms that separate and extract the atrial rhythm starting from a prior estimation of the main atrial frequency. The first one is an algebraic method based on the maximization of a cost function that measures the periodicity. The other one is an adaptive algorithm that exploits the decorrelation of the atrial and other signals diagonalizing the correlation matrices at multiple lags of the period of atrial activity. The algorithms are applied successfully to synthetic and real data. In simulated ECGs, the average correlation index obtained was 0.811 and 0.847, respectively. In real ECGs, the accuracy of the results was validated using spectral and temporal parameters. The average peak frequency and spectral concentration obtained were 5.550 and 5.554 Hz and 56.3 and 54.4%, respectively, and the kurtosis was 0.266 and 0.695. For validation purposes, we compared the proposed algorithms with established methods, obtaining better results for simulated and real registers.

  19. Chronic treatment with trimetazidine reduces the upregulation of atrial natriuretic peptide in heart failure

    USDA-ARS?s Scientific Manuscript database

    Trimetazidine (TMZ) is effective for the treatment of ischemic cardiomyopathy; however, little is known about the effect of TMZ in established injury-induced heart failure. When rats with established infarct-induced heart failure were treated for 12 weeks with TMZ there was no effect on left ventric...

  20. Atrial natriuretic peptide in the rat brain and plasma during clinical death and after resuscitation.

    PubMed

    Kapuściński, A

    1994-01-01

    By means of the radioimmunologic method changes of ANP content in the rat brain and plasma have been evaluated during 5-min clinical death and up to 2 hr after resuscitation. Ischemia did not produce significant rise of ANP immunoreactivity in the brain, however, in the early postresuscitation period its reversible increase was noted with the peak value at 15th min. The content of peptide in plasma significantly increased at the end of clinical death and 5 min after resuscitation. The obtained results can support the notion of quantitative relationship between concentration of ANP and cGMP content in the brain in vivo.

  1. Distribution and elimination of intravenously administered atrial natriuretic hormone(ANH) to normal and nephrectomized rats

    SciTech Connect

    Devine, E.; Artman, L.; Budzik, G.; Bush, E.; Holleman, W.

    1986-05-01

    The 24 amino acid peptide, ANH(5-28), was N-terminally labeled with I-125 Bolton-Hunter reagent, iodo-N-succinimidyl 3-(4-hydroxyphenyl)propionate. The I-125 peptide plus 1..mu..g/kg of the I-127 Bolton-Hunter peptide was injected into normal and nephrectomized anesthetized (Nembutal) rats. Blood samples were drawn into a cocktail developed to inhibit plasma induced degradation. Radiolabeled peptides were analyzed by HPLC. A biphasic curve of I-125 ANH(5-28) elimination was obtained, the first phase (t 1/2 = 15 sec) representing in vivo distribution and the second phase (t 1/2 = 7-10 min) a measurement of elimination. This biphasic elimination curve was similar in normal and nephrectomized rats. The apparent volumes of distribution were 15-20 ml for the first phase and > 300 ml for the second phase. In order to examine the tissue distribution of the peptide, animals were sacrificed at 2 minutes and the I-125 tissue contents were quantitated. The majority of the label was located in the liver (50%), kidneys (21%) and the lung (5%). The degradative peptides appearing in the plasma and urine of normal rats were identical. No intact radiolabeled ANH(5-28) was found in the urine. In conclusion, iodinated Bolton-Hunter labeled ANH(5-28) is rapidly removed from the circulation by the liver and to a lesser extent by the kidney, but the rate of elimination is not decreased by nephrectomy.

  2. Surgery for Atrial Fibrillation

    PubMed Central

    Lawrance, Christopher P.; Henn, Matthew C.; Damiano, Ralph J.

    2015-01-01

    Synopsis Atrial fibrillation is the most common cardiac arrhythmia and its treatment options include drug therapy or, catheter-based or surgical interventions. The surgical treatment of atrial fibrillation has undergone multiple evolutions over the last several decades. The Cox-Maze procedure which was developed by James Cox in 1987 is a procedure where multiple surgical incisions are created along the atria to interrupt the electrical pathways thought to allow atrial fibrillation to persist. This procedure went on to become the gold standard for the surgical treatment of atrial fibrillation and is currently in its 4th iteration called the Cox-Maze IV. The Cox-Maze IV replaced the previous “cut-and-sew” method with a combination of cryoablation and bipolar RF ablation. The adaption of ablation technologies allowed the Cox-Maze IV procedure to be performed through a less invasive right minithoracotomy instead of a traditional sternotomy approach. The aim of this article is to review the indications and preoperative planning for performing a Cox-Maze IV procedure. A description of the operative techniques for both a sternotomy and right mini-thoracotomy approach will be discussed in addition to specific postoperative considerations. Finally, this article will review the literature describing the surgical results for both approaches including comparisons of the Cox-Maze IV to the previous “cut-and-sew” method. PMID:25443237

  3. Augmented potassium current is a shared phenotype for two genetic defects associated with familial atrial fibrillation

    PubMed Central

    Abraham, Robert L; Yang, Tao; Blair, Marcia; Roden, Dan M; Darbar, Dawood

    2009-01-01

    Background Mutations in multiple genes have been implicated in familial atrial fibrillation (AF), but the underlying mechanisms, and thus implications for therapy, remain ill-defined. Methods and Results Among 231 participants in the Vanderbilt AF Registry, we found a mutation in KCNQ1 (encoding the α-subunit of slow delayed rectifier potassium current [IKs]) and separately a mutation in natriuretic peptide precursor A (NPPA) gene (encoding atrial natriuretic peptide, ANP), both segregating with early-onset lone AF in different kindreds. The functional effects of these mutations yielded strikingly similar IKs “gain of function.” In Chinese Hamster Ovary (CHO) cells, coexpression of mutant KCNQ1 with its ancillary subunit KCNE1 generated ~3-fold larger currents that activated much faster than wild-type (WT)-IKs. Application of the WT NPPA peptide fragment produced similar changes in WT-IKs, and these were exaggerated with the mutant NPPA S64R peptide fragment. Anantin, a competitive ANP receptor antagonist, completely inhibited the changes in IKs gating observed with NPPA-S64R. Computational simulations identified accelerated transitions into open states as the mechanism for variant IKs gating. Incorporating these IKs changes into computed human atrial action potentials (AP) resulted in 37% shortening (120 vs. 192 ms at 300 ms cycle length), reflecting loss of the phase II dome which is dependent on L-type calcium channel current. Conclusions We found striking functional similarities due to mutations in KCNQ1 and NPPA genes which led to IKs “gain of function”, atrial AP shortening, and consequent altered calcium current as a common mechanism between diverse familial AF syndromes. PMID:19646991

  4. Does the relationship between natriuretic hormones and diastolic function differ by race?

    PubMed

    Kapuku, Gaston K; Davis, Harry C; Thomas, Patrick; Januzzi, James; Harshfield, Gregory A

    2012-08-01

    Heart failure develops earlier and is more prevalent in blacks than whites because of their higher incidence of hypertension and diabetes and likely subsequent diastolic dysfunction. Natriuretic peptides (NP) prevent cardiac malfunction through pressure, natriuresis action. However, whether race affects the relationships of NP action with cardiac function is unknown. To assess this, 55 (21 whites and 27 males) normotensive adults underwent a 2-hour protocol of 40 minutes rest, video game stressor and recovery. Mitral inflow and myocardial velocities (tissue Doppler) were recorded every 20 minutes. Blood pressure and heart rate were obtained at 10-minute intervals. Blood samples for pro-atrial NP and pro-brain NP (pro-BNP) were collected every 40 minutes. There were differences in the association between (1) the changes from rest to stress for E/A ratio and double product (whites, r = -0.42; blacks, r = 0. 10; P = 0.034 for difference between correlations); (2) stress E(m) and pro-atrial NP (whites, r = 0.59; blacks, r = -0.25; P = 0.025); (3) rest E(m) and BNP (whites, r = 0.83; blacks r = -0.17; P = 000); (4) rest E(m)/A(m) and pro-BNP (whites, r = 0.70; blacks, r = -0.42; P = 0.003); (5) rest E/E(m) and pro-BNP (whites, r = -0.61; blacks, r = 0.31; P = 0.015) and (6) stress E and pro-BNP (whites, r = 0.56; blacks, r = -0.18; P = 0.043). The higher correlations between levels of NP and diastolic function indices both at rest and stress suggest that NP protective action is more pronounced in whites than in blacks.

  5. Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature.

    PubMed

    Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L Maximilian; Gregoric, Igor D

    2016-06-01

    We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions.

  6. Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature

    PubMed Central

    Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L. Maximilian

    2016-01-01

    We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240

  7. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    PubMed Central

    Abdelalim, Essam M.; Bellier, Jean-Pierre; Tooyama, Ikuo

    2016-01-01

    Brain natriuretic peptide (BNP) exerts its functions through NP receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn (DH) of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and dorsal root ganglion (DRG). BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the DH of the spinal cord and in the neurons of the intermediate column (IC) and ventral horn (VH). Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I–II) labeled with calcitonin gene-related peptide (CGRP), suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase (ChAT) in the motor neurons of the VH. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NP receptor-A (NPR-A) and/or NP receptor-B (NPR-B) at the spinal cord level. PMID:27994541

  8. Rationale and therapeutic opportunities for natriuretic peptide system augmentation in heart failure.

    PubMed

    McKie, Paul M; Burnett, John C

    2015-02-01

    The natriuretic peptide system (NPS) is intimately involved in cardiorenal homeostasis in health, and dysregulation of the NPS plays an important role in the pathophysiology of heart failure (HF). Indeed, the diuretic, vasorelaxation, beneficial remodeling, and potent neurohumoral inhibition of the NPS support the therapeutic development of chronic augmentation of the NPS in symptomatic HF. Further, chronic augmentation of the protective NPS and in early stages of HF may ultimately prevent the progression of HF and reduced subsequent morbidity and mortality. In the current manuscript, we review the rationale for as well as previous and current efforts aimed at chronic therapeutic augmentation of the NPS in HF.

  9. Association of left atrial endothelin-1 with atrial rhythm, size, and fibrosis in patients with structural heart disease.

    PubMed

    Mayyas, Fadia; Niebauer, Mark; Zurick, Andrew; Barnard, John; Gillinov, A Marc; Chung, Mina K; Van Wagoner, David R

    2010-08-01

    Atrial fibrillation (AF) promotes atrial remodeling and can develop secondary to heart failure or mitral valve disease. Cardiac endothelin-1 (ET-1) expression responds to wall stress and can promote myocyte hypertrophy and interstitial fibrosis. We tested the hypothesis that atrial ET-1 is elevated in AF and is associated with AF persistence. Left atrial appendage tissue was studied from coronary artery bypass graft, valve repair, and/or Maze procedure in patients in sinus rhythm with no history of AF (SR, n=21), with history of AF but in SR at surgery (AF/SR, n=23), and in AF at surgery (AF/AF, n=32). The correlation of LA size with atrial protein and mRNA expression of ET-1 and ET-1 receptors (ETAR and ETBR) was evaluated. LA appendage ET-1 content was higher in AF/AF than in SR, but receptor levels were similar. Immunostaining revealed that ET-1 and its receptors were present both in atrial myocytes and in fibroblasts. ET-1 content was positively correlated with LA size, heart failure, AF persistence, and severity of mitral regurgitation. Multivariate analysis confirmed associations of ET-1 with AF, hypertension, and LA size. LA size was associated with ET-1 and MR severity. ET-1 mRNA levels were correlated with genes involved in cardiac dilatation, hypertrophy, and fibrosis. Elevated atrial ET-1 content is associated with increased LA size, AF rhythm, hypertension, and heart failure. ET-1 is associated with atrial dilatation, fibrosis, and hypertrophy and probably contributes to AF persistence. Interventions that reduce atrial ET-1 expression and/or block its receptors may slow AF progression.

  10. TGF-beta1 expression and atrial myocardium fibrosis increase in atrial fibrillation secondary to rheumatic heart disease.

    PubMed

    Xiao, Hua; Lei, Han; Qin, Shu; Ma, Kanghua; Wang, Xi

    2010-03-01

    Atrial fibrosis was considered a structural basis for the development and sustaining of atrial fibrillation (AF). Transforming growth factor-beta1 (TGF-beta1) was one of the main factors for accelerating collagen production. The contribution of TGF-beta1 in the pathogenesis of AF needs further investigation. The altered expression and distribution of TGF-beta1 will be associated with the changes in atrial fibrosis in different types of AF patients with rheumatic heart disease (RHD). Right atrial specimens obtained from 38 RHD patients undergoing mitral valve replacement surgery were divided into 3 groups: the sinus rhythm group (n = 8), the paroxysmal AF group (pAF; n = 10), and the chronic AF group (cAF; AF lasting >/= 6 mo; n = 20). The degree of atrial fibrosis, collagen content, serum levels, messenger RNA (mRNA), and protein expression of TGF-beta1 were detected. The collagen content, serum level, TGF-beta1 mRNA, and protein expression of the atrial tissue increased gradually in sinus rhythm, for both pAF and cAF groups, respectively. A positive correlation between TGF-beta1 and the degree of atrial fibrosis was also demonstrated (P < 0.05). The TGF-beta1 expression in atrial tissue increased gradually in proportion to the degree of atrial fibrosis in AF and was associated with the type of AF, which suggests that TGF-beta1 is possibly involved in the pathogenesis of AF in RHD patients. Copyright (c) 2010 Wiley Periodicals, Inc.

  11. Cardiopulmonary involvement in Puumala hantavirus infection.

    PubMed

    Rasmuson, Johan; Lindqvist, Per; Sörensen, Karen; Hedström, Magnus; Blomberg, Anders; Ahlm, Clas

    2013-10-28

    Hantavirus infections cause potentially life-threatening disease in humans world-wide. Infections with American hantaviruses may lead to hantavirus pulmonary syndrome characterised by severe cardiopulmonary distress with high mortality. Pulmonary involvement in European Puumala hantavirus (PUUV) infection has been reported, whereas knowledge of potential cardiac manifestations is limited. We aimed to comprehensively investigate cardiopulmonary involvement in patients with PUUV-infection. Twenty-seven hospitalised patients with PUUV-infection were examined with lung function tests, chest high-resolution CT (HRCT), echocardiography including speckle tracking strain rate analysis, ECG and measurements of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and troponin T. Patients were re-evaluated after 3 months. Twenty-five age and sex-matched volunteers acted as controls for echocardiography data. Two-thirds of the patients experienced respiratory symptoms as dry cough or dyspnoea. Gas diffusing capacity was impaired in most patients, significantly improving at follow-up but still subnormal in 38%. HRCT showed thoracic effusions or pulmonary oedema in 46% of the patients. Compared to controls, the main echocardiographic findings in patients during the acute phase were significantly higher pulmonary vascular resistance, higher systolic pulmonary artery pressure, lower left ventricular ejection fraction and impaired left atrial myocardial motion. Pathological ECG, atrial fibrillation or T-wave changes, was demonstrated in 26% of patients. NT-ProBNP concentrations were markedly increased and were inversely associated with gas diffusing capacity but positively correlated to pulmonary vascular resistance. Furthermore, patients experiencing impaired general condition at follow-up had significantly lower gas diffusing capacity and higher pulmonary vascular resistance, compared to those feeling fully recovered. In a majority of patients with PUUV

  12. Posterior left atrial wall hematoma mimicking cystic intracavitary atrial mass.

    PubMed

    Bahnacy, Yasser; Suresh, Cheriyil; Dawoud, Hamed; Zubaid, Mohammad

    2010-10-01

    Atrial myxoma is the most common benign primary tumor of the heart most commonly in the left atrium (LA). Cystic or cavitated intracardiac masses are rare. We report the case of a 43-year-old male patient admitted with chest infection, hemoptysis, and severe respiratory distress, who had to be ventilated. Chest computed tomography showed bilateral lung consolidation with large mass occupying the region of the LA. Transthoracic echocardiography and transesophageal echocardiography showed a large intracavitary left atrial cystic mobile mass. Open-heart surgical exploration did not show any mass inside the LA. A posterior left atrial wall hematoma was found and evacuated. Biopsies confirmed the presence of blood clots. Posterior left atrial wall hematoma may appear as left atrial intracavitary cystic mass and should be included in the differential diagnosis of cystic left atrial mass.

  13. Genetics Home Reference: familial atrial fibrillation

    MedlinePlus

    ... Home Health Conditions familial atrial fibrillation familial atrial fibrillation Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Familial atrial fibrillation is an inherited condition that disrupts the heart's ...

  14. α-Adrenoceptor blockade modifies neurally induced atrial arrhythmias

    PubMed Central

    Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L.; Armour, John Andrew

    2008-01-01

    Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by α-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (α1-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (α2-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined α-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by α1,2-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal α-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that α-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system. PMID:18716036

  15. Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation.

    PubMed

    Hijazi, Ziad; Oldgren, Jonas; Siegbahn, Agneta; Wallentin, Lars

    2017-01-01

    Atrial fibrillation is the most common sustained arrhythmia and an important contributor to cardiovascular morbidity and mortality. Several strategies have been proposed for prediction of outcomes and individualization of treatments to better balance the benefits of stroke prevention and risks of bleeding during anticoagulation. The availability of analytically more specific and sensitive methods to measure circulating biomarkers of cellular and organ stress and dysfunction has led to testing of their utility in several cardiovascular conditions. In patients with atrial fibrillation, biomarkers of myocardial injury (troponin) and cardiovascular stress and dysfunction (natriuretic peptides, growth differentiation factor 15), myocardial fibrosis (galectin-3), renal dysfunction (creatinine, cystatin C), inflammation (C-reactive protein, cytokines) and coagulation activity (d-dimer) have been found associated with underlying pathophysiology, clinical outcomes and effects of treatment. Measurements of these markers might therefore expand the understanding of the pathophysiology, improve risk assessment and optimize treatment in individual patients with atrial fibrillation. Biomarkers for risk stratification have potential roles as tools for evaluation of patients with atrial fibrillation and for selection of the best treatment strategies to prevent stroke, major bleeding, and mortality. © 2016 American Association for Clinical Chemistry.

  16. Impact of electrical cardioversion for atrial fibrillation on left atrial appendage function and spontaneous echo contrast: characterization by simultaneous transesophageal echocardiography.

    PubMed

    Grimm, R A; Stewart, W J; Maloney, J D; Cohen, G I; Pearce, G L; Salcedo, E E; Klein, A L

    1993-11-01

    This study assessed the function of the left atrial appendage in the pericardioversion period to gain insights into mechanisms involved in thromboembolism after cardioversion of atrial fibrillation. Systemic embolization associated with electrical cardioversion of atrial fibrillation is thought to originate from the left atrium or left atrial appendage, or both. However, the mechanism involved is poorly understood. We studied left atrial appendage function with transesophageal echocardiography in 20 patients with atrial fibrillation before and after successful electrical cardioversion. We measured left atrial appendage emptying and filling velocities by pulsed wave Doppler echocardiography, characterized Doppler emptying patterns, measured atrial appendage areas and assessed the presence or absence of spontaneous echo contrast or thrombus. Organized left atrial appendage function returned in 16 (80%) of 20 patients immediately after cardioversion. Atrial appendage emptying velocities before cardioversion were greater in patients without (0.39 +/- 0.02 m/s) than in those with (0.25 +/- 0.12 m/s) spontaneous echo contrast (p = 0.045). Furthermore, emptying velocities before cardioversion were significantly greater than late diastolic emptying velocities after cardioversion (0.31 +/- 0.15 vs. 0.14 +/- 0.12 m/s, p = 0.0001), as well as in both the group with (0.25 +/- 0.12 vs. 0.13 +/- 0.13 m/s, p = 0.001) and the group without (0.39 +/- 0.02 vs. 0.15 +/- 0.12 m/s, p = 0.01) spontaneous echo contrast. In addition, left atrial and atrial appendage spontaneous echo contrast developed in 4 of 20 patients and increased in intensity in 3 of 20 patients in the immediate postcardioversion period. Organized left atrial appendage function returns in most patients immediately after cardioversion of atrial fibrillation. However, its function is impaired compared with that before cardioversion. Furthermore, spontaneous echo contrast increased in 7 (35%) of 20 patients after

  17. [The effect of atrial pacing on left ventricular diastolic function and BNP levels in patients with DDD pacemaker].

    PubMed

    Apali, Zeynep; Bayata, Serdar; Yeşil, Murat; Arikan, Erdinç; Postaci, Nursen

    2010-08-01

    We aimed to investigate the effect of atrial pacing on left ventricular diastolic function and brain natriuretic peptide (BNP) levels in patients with DDD pacemaker. Thirty patients with complete atrio-ventricular (AV) block and DDD pacemaker were included. All patients had normal left ventricular systolic function. Echocardiographic diastolic function parameters (transmitral and tissue Doppler velocities during early (E and E') and late (A and A') filling) and NT-pro-BNP levels were evaluated prospectively during atrial sensing and pacing periods. Echocardiographic data were compared with paired sample t test and NT-pro-BNP levels were compared with Wilcoxon test. Echocardiographic E/A, E'/A', E/E' ratios were calculated as 0.72+/-0.34, 0.61+/-0.21 and 8.76+/-2.58 during atrial sensing period. Same parameters were found as 0.71+/-0.23, 0.64+/-0.16 and 8.93+/-3.16 respectively during atrial pacing period. Echocardiographic left ventricular diastolic function parameters were not significantly different during atrial pacing and atrial sensing periods. Median plasma NT-pro-BNP levels were measured as 142 pg/ml (min-max 47-563 pg/ml) and 147 pg/ml (min-max 33-1035 pg/ml) during atrial sensing and pacing periods respectively. These levels were not significantly different (p=0.86). The result of this study has shown that, atrial pacing has not any additional detrimental effect on left ventricular diastolic function parameters in paced patients with normal left ventricular systolic function.

  18. A new atrial septostomy technique.

    PubMed

    Park, S C; Zuberbuhler, J R; Neches, W H; Lenox, C C; Zoltun, R A

    1975-01-01

    Balloon atrial septostomy is usually ineffective if the atrial septum is