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1

Pregnancy-Induced Hypertension  

MedlinePLUS

... Pregnancy-induced hypertension (PIH), also called toxemia or preeclampsia: This condition can cause serious problems for both ... delivery for my baby? Source NHBPEP Report on High Blood Pressure in Pregnancy: A Summary for Family Physicians by MA Zamorski, ...

2

PLATELET ESTIMATION : ITS PROGNOSTIC VALUE IN PREGNANCY INDUCED HYPERTENSION  

Microsoft Academic Search

Thrombocytopenia is an associated phenomenon of Pregnancy induced hypertension (PIH). But the accurate count of platelets either by manual, (direct or indirect methods) or by automated cell counters is not feasible for all patients at all hospitals. Therefore we have adopted the method of platelet estimation, not platelet count as an alternate procedure to estimate the degree of thrombocytopenia in

S. MOHAPATRA; B. B. PRADHAN; U. K. SATPATHY; ARATI MOHANTY; J. R. PATTNAIK

3

Pregnancy-induced hypertension and infant growth at 28 and 42 days postpartum  

Microsoft Academic Search

BACKGROUND: No previous studies have examined the effect of pregnancy-induced hypertension (PIH) on early infant growth. The objective was to study infant growth patterns of babies born to mothers with PIH at 28 and 42 days postpartum. METHODS: DESIGN: We conducted a population-based retrospective cohort study of 16,936 pregnancies delivered between January 1, 1989 through December 31, 1990 in Suzhou,

Emmanuelle Baulon; William D Fraser; Bruno Piedboeuf; Pierre Buekens; Xu Xiong

2005-01-01

4

The effects of smoking and hypertensive disorders on fetal growth  

Microsoft Academic Search

BACKGROUND: It is well known that smoking and pregnancy induced hypertension (PIH) are associated with decreased fetal growth. It has been reported that in preeclampsia the fetal growth deficit attributable to smoking is higher, which has been contradicted in other studies. We therefore evaluated the effects on fetal growth of early- and late onset PIH and chronic hypertension and how

Svein Rasmussen; Lorentz M Irgens

2006-01-01

5

Levels of erythrocyte malonyldialdehyde, vitamin E, reduced glutathione, G6PD activity & plasma urate in patients of pregnancy induced hypertension.  

PubMed

To assess the oxidative stress across the cell membrane in patients suffering from pregnancy induced hypertension, erythrocyte malonyldialdehyde, vitamin E, reduced glutathione, glucose-6-phosphate dehydrogenase activity and plasma urate levels were estimated in 25 non pregnant women, 40 normotensive pregnant women and 40 women with pregnancy induced hypertension (PIH). As compared to non pregnant women, there was a significant increase in the levels of erythrocyte malonyldialdehyde and plasma urate in normotensive pregnant women, which were further increased in women with PIH. Erythrocyte glutathione levels were raised in normotensive pregnant women as compared to non pregnant women. Its levels were decreased in patients of PIH as compared to normotensive pregnant women. Cellular bio-availability of vitamin E was depressed in both normotensive pregnancy as well as patients with pregnancy induced hypertension as compared to non pregnant women. PMID:7927548

Kabi, B C; Goel, N; Rao, Y N; Tripathy, R; Tempe, A; Thakur, A S

1994-07-01

6

Lower segment cesarean section in a patient with severe thrombocytopenia and pregnancy induced hypertension  

PubMed Central

Thrombocytopenia in pregnancy carries a major risk of feto-maternal morbidity and mortality. We present a case of hypocellular bone marrow with severe thrombocytopenia with pregnancy induced hypertension (PIH) for emergency lower segment cesarean section (LSCS). This disease is characterized by pancytopenia and hypocellular bone marrow with impaired morphology and maturation. Causes of death due to this disease include hemorrhage and infection secondary to thrombocytopenia and neutropenia especially following surgery. We report successful management of emergency LSCS with severe thrombocytopenia with severe PIH. PMID:24106368

Harde, Minal; Dave, Sona; Vasave, Rahul Ramji; Gujjar, Pinakin; Bhadade, Rakesh

2013-01-01

7

A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension  

PubMed Central

Objectives Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B12, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B12 and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH). Materials and Methods Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B12; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B12 + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation. Results Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–?) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-? levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group. Conclusion Key constituents of one carbon cycle (folic acid, vitamin B12 and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia. PMID:25405347

Kemse, Nisha G.; Kale, Anvita A.; Joshi, Sadhana R.

2014-01-01

8

[Case of postpartum intracerebral hemorrhage due to pregnancy induced hypertension].  

PubMed

A 32-year-old woman, gravida 0, para 0, was admitted to the obstetrics department of our hospital after a cesarean section at 35 weeks of gestation. The cesarean section was performed because pregnancy induced hypertension (PIH) had worsened. The next day, she suddenly became drowsy and developed right hemiparesis and anisocoria. Computed tomography of the brain showed intracerebral hemorrhage in the parietal lobe with uncal herniation. She underwent an urgent craniotomy and removal of the hematoma. Five days later, magnetic resonance angiography (MRA) of the brain showed vasospasm of the bilateral intracranial internal carotid arteries, middle cerebral arteries, and anterior cerebral arteries. Thirteen days later, cerebral angiography showed cessation of vasospasm and vascular abnormalities such as moyamoya disease, arteriovenous malformation and cerebral aneurysm were not observed. Twenty-one days later, MRA showed the absence of vasospasm in those arteries, but her right hemiparesis and sensory aphasia persisted. Twenty-six days later, she was transferred to another hospital for further rehabilitation. Neurosurgeons should be aware of the possibility of intracerebral hemorrhage caused by PIH. In this manuscript, we provide a case presentation and review of the literature. PMID:22128271

Matsuda, Ryosuke; Fujimoto, Takatoshi; Tamura, Kentaro; Motoyama, Yasushi; Park, Young-Su; Nakase, Hiroyuki

2011-12-01

9

Impact of Computer-Based Pregnancy-Induced Hypertension and Diabetes Decision Aids on Empowering Pregnant Women  

PubMed Central

Objectives We designed a computer-based decision aid (CDA) for use by pregnant women at home to investigate and participate in solving their pregnancy problems related to pregnancy-induced hypertension (PIH) and gestational diabetes (GD). The system cannot and is not intended to replace visits to physicians; rather it can help women focus on the most important symptoms and provides guidance on when to see a doctor. Methods The study is a randomized controlled trial, which is performed among Iranian pregnant women. For subjects, 420 healthy pregnant women have been recruited from two private and two public prenatal centers. The intervention group will receive the CDA for use at home, and the control group will receive care as usual. The CDA relies on knowledge extracted from the national guidelines on PIH and GD. Results The two primary outcomes for the study are self-efficacy and knowledge. Self-efficacy will be measured by the Stanford self-efficacy scale and knowledge will be evaluated by 15 binary (true/false) questions provided by the researchers. Secondary outcomes include type and frequency of doctor and/or medical center visits; blood pressure and blood sugar changes based on the national guidelines and according to pregnancy records, and anxiety will be assessed by the state component of the short Spielberger anxiety scale. Conclusions This paper describes the design of a CDA and a protocol for a randomized controlled trial to study the effects of the CDA on self-efficacy and knowledge of pregnant women pertaining to PIH and GD. Differences in the primary outcomes will be analyzed using 'intention-to-treat' principles.

Aslani, Azam; Tara, Fatemeh; Ghalighi, Lila; Pournik, Omid; Ensing, Sabine; Abu-Hanna, Ameen

2014-01-01

10

Alcohol-induced hypertension: Mechanism and prevention  

PubMed Central

Epidemiological, preclinical and clinical studies established the association between high alcohol consumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been proposed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angiotensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to increase in intracellular calcium levels, stimulation of the endothelium to release vasoconstrictors and loss of relaxation due to inflammation and oxidative injury of the endothelium leading to inhibition of endothelium-dependent nitric oxide production. Loss of relaxation due to inflammation and oxidative injury of the endothelium by angiotensin II leading to inhibition of endothelium-dependent nitric oxide production is the major contributors of the alcohol-induced hypertension. For the prevention of alcohol-induced hypertension is to reduce the amount of alcohol intake. Physical conditioning/exercise training is one of the most important strategies to prevent/treat chronic alcohol-induced hypertension on physiological basis. The efficacious pharmacologic treatment includes the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs) which have antioxidant activity and calcium channel blockers. The most effective prevention and treatment of alcohol-induced hypertension is physical exercise and the use of ACE inhibitors or ARBs in the clinic PMID:24891935

Husain, Kazim; Ansari, Rais A; Ferder, Leon

2014-01-01

11

Sildenafil attenuates placental ischemia-induced hypertension  

PubMed Central

Preeclampsia is a complication of pregnancy that is marked by hypertension, proteinuria, and maternal endothelial dysfunction. A central factor in the etiology of the disease is the development of placental hypoxia/ischemia, which releases pathogenic soluble factors. There is currently no effective treatment for preeclampsia, but the phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been suggested, as PDE-5 is enriched in the uterus, and its antagonism could improve uteroplacental function. Here, we report in the reduced uterine perfusion pressure (RUPP) rat model that administration of oral sildenafil is effective in attenuating placental ischemia-induced hypertension during gestation. RUPP animals have significantly elevated arterial pressure compared with control animals (132 ± 3 vs. 100 ± 2 mmHg; P < 0.05). Administration of oral sildenafil (45 mg·kg?1·day?1) had no effect on blood pressure in control rats but decreased pressure in RUPP rats (115 ± 1 mmHg; P < 0.05). RUPP induced changes in placental sFlt-1, and vascular endothelial growth factor (VEGF) was unaffected by sildenafil administration, as was the decrease in free plasma VEGF. RUPP animals had a significant increase in medullary PDE-5/?-actin ratio (1 ± 0.14 vs. 1.63 ± 0.18; P < 0.05) expression with a resulting reduction in renal medullary cGMP (1.5 ± 0.15 vs. 0.99 ± 0.1 pmol/?g protein, P < 0.05) compared with controls. Although sildenafil had no effect on renal medullary cGMP in control animals, it significantly increased cGMP in RUPP animals (1.3 ± 0.1 pmol/?g protein; P < 0.05). These data suggest that sildenafil might provide an effective therapeutic option for the management of hypertension during preeclampsia. PMID:23785075

George, Eric M.; Palei, Ana C.; Dent, Edward A.

2013-01-01

12

Mechanisms of antiangiogenic-induced arterial hypertension.  

PubMed

Antiangiogenic therapy has emerged as an important concept in the treatment of solid tumors. Vascular endothelial growth factor (VEGF) represents an important therapeutic target, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. Arterial hypertension has been commonly reported in all clinical trials testing inhibitors of angiogenesis (especially inhibitors of VEGF/VEGFR-2 signalling), with incidence ranging from 11% to 43% in all studies. The mechanism of elevated blood pressure in patients treated with antiangiogenic agents is not fully understood, but it is probably multifactorial, involving endothelial dysfunction and capillary rarefaction. Recently, several studies have suggested that early blood pressure rise was associated with better antitumoral efficacy and improved prognosis, making this commonly observed effect a promising marker of efficacy. PMID:21479992

Mourad, Jean-Jacques; Levy, Bernard I

2011-08-01

13

Spaceflight-Induced Intracranial Hypertension: An Overview  

NASA Technical Reports Server (NTRS)

This slide presentation is an overview of the some of the known results of spaceflight induced intracranial hypertension. Historical information from Gemini 5, Apollo, and the space shuttle programs indicated that some vision impairment was reported and a comparison between these historical missions and present missions is included. Optic Disc Edema, Globe Flattening, Choroidal Folds, Hyperopic Shifts and Raised Intracranial Pressure has occurred in Astronauts During and After Long Duration Space Flight. Views illustrate the occurrence of Optic Disc Edema, Globe Flattening, and Choroidal Folds. There are views of the Arachnoid Granulations and Venous return, and the question of spinal or venous compliance issues is discussed. The question of increased blood flow and its relation to increased Cerebrospinal fluid (CSF) is raised. Most observed on-orbit papilledema does not progress, and this might be a function of plateau homeostasis for the higher level of intracranial pressure. There are seven cases of astronauts experiencing in flight and post flight symptoms, which are summarized and follow-up is reviewed along with a comparison of the treatment options. The question is "is there other involvement besides vision," and other Clinical implications are raised,

Traver, William J.

2011-01-01

14

Platelet-Activating Factor and Bacteremia-Induced Pulmonary Hypertension  

Microsoft Academic Search

Background. Acute lung injury is a common complication of gram-negative sepsis. Pulmonary hypertension and increased lung vascular permeability are central features of lung injury following experimental bacteremia. Platelet-activating factor is a prominent proinflammatory mediator during bacterial sepsis. Our previous studies have demonstrated that exogenous administration of platelet-activating factor (PAF) induces pulmonary edema without causing pulmonary hypertension. Interestingly, inhibition of PAF

Leonardo C Clavijo; Mary B Carter; Paul J Matheson; Lisa A Wills-Frank; Mark A Wilson; William B Wead; R. Neal Garrison

2000-01-01

15

Melatonin prevents neonatal dexamethasone induced programmed hypertension: Histone deacetylase inhibition.  

PubMed

Adulthood hypertension can be programmed by corticosteroid exposure in early life. Oxidative stress, epigenetic regulation by histone deacetylases (HDACs), and alterations of renin-angiotensin system (RAS) are involved in the developmental programming of hypertension. We examined whether melatonin prevented neonatal dexamethasone (DEX)-induced programmed hypertension and how melatonin prevented these processes. We also examined whether HDAC inhibition by trichostatin A (TSA, a HDAC inhibitor) had similar effects. Male offspring were assigned to 5 groups (n=6/group): control, DEX, melatonin, DEX+melatonin, and DEX+TSA. Male rat pups were injected i.p. with DEX on day 1 (0.5mg/kg BW), day 2 (0.3mg/kg BW), and day 3 (0.1mg/kg BW) after birth. Melatonin was administered in drinking water at the dose of 0.01% during the lactation period. The DEX+TSA group received DEX and 0.5mg/kg TSA subcutaneous injection once daily for 1 week. All rats were killed at 16 weeks of age. Neonatal DEX exposure induced hypertension in male offspring at 16 weeks of age, which melatonin prevented. Neonatal DEX exposure decreased gene expression related to apoptosis, nephrogenesis, RAS, and sodium transporters. Yet DEX treatment increased protein levels of HDAC-1, -2, and -3 in the kidney. Melatonin therapy preserved the decreases of gene expression and decreased HDACs. Similarly, HDAC inhibition prevented DEX-induced programmed hypertension. In conclusion, melatonin therapy exerts a long-term protection against neonatal DEX-induced programmed hypertension. Its beneficial effects include alterations of RAS components and inhibition of class I HDACs. Given that the similar protective effects of melatonin and TSA, melatonin might inhibit HDACs to epigenetic regulation of hypertension-related genes to prevent programmed hypertension. PMID:25090636

Wu, Ting-Hsin; Kuo, Hsuan-Chang; Lin, I-Chun; Chien, Shao-Ju; Huang, Li-Tung; Tain, You-Lin

2014-10-01

16

Noise induced hypertension and prehypertension in Pakistan.  

PubMed

The present study investigates the relationship of different sound levels with hypertension and prehypertension in Pakistani population. A cross sectional study was conducted to determine the prevalence of hypertension and prehypertension due to exposure of sound level ?80 dBA (A weighted sound pressure level), 81-94 dBA and ?95 dBA in November 11, 2005 to January 30, 2007. Sites were selected with stable sound ranges according to the above mentioned criteria. After selecting sampling sites, workers living in that area for at least 8 hours per day were categorized on the basis of blood pressure in groups called as normotensive, prehypertensive and hypertensive. Persons with diabetes, chronic bacterial or viral infections, alcohol addiction, kidney problems were excluded from the study. For getting homogenous groups, age range of 30-50 years was selected. Out of 566 samples, 90 excluded samples were consisted of 8% diabetic patients, 5% hepatitis C patients, 3% hepatitis B patients and 0% AIDS patients. Out of 476 participants, 389 samples were found with age 40±10 years. High noise increased the risks of hypertension (Odds ratio: 4.41; Confidence interval: 2,123-9,196) and prehypertension (Odds ratio: 3,809; Confidence Interval: 1,804-8,042) as compared to the normal sound level. However increased chances of hypertension (Odds ratio: 2,271; Confidence interval: 1,043-4,946) and prehypertension (Odds ratio: 3,028; Confidence Interval: 1,440-6,367) were observed on median noise exposure also. These findings suggest that sound level more than 81 dBA increases the chances for development of hypertension and prehypertension in Pakistani population. PMID:20846132

Nawaz, Syed Kashif; Hasnain, Shahida

2010-08-01

17

Hypertension  

MedlinePLUS

... can all be a culprit. Why Hypertension Is Dangerous Instead of asking "What is hypertension?" the better question may be, "Why is hypertension dangerous?" When you have high blood pressure, your heart ...

18

Excellent Tolerance to Cilnidipine in Hypertensives with Amlodipine - Induced Edema  

PubMed Central

Background: Ankle edema is a common adverse effect of amlodipine, an L-type calcium channel blocker (CCB). Cilnidipine is a newer L/N-type CCB, approved for treatment of essential hypertension. Aim: This study was designed to determine whether cilnidipine can produce resolution of amlodipine-induced edema while maintaining adequate control of hypertension. Materials and Methods: A prospective study was performed on 27 patients with essential hypertension with amlodipine-induced edema. Concomitant nephropathy, cardiac failure, hepatic cirrhosis, or other causes of edema, and secondary hypertension were excluded by appropriate tests. Amlodipine therapy was substituted in all the cases with an efficacy-equivalent dose of cilnidipine. Clinical assessment of ankle edema and measurement of bilateral ankle circumference, body weight, blood pressure, and pulse rate were performed at onset of the study and after 4 weeks of cilnidipine therapy. Results: At completion of the study, edema had resolved in all the patients. There was a significant decrease in bilateral ankle circumference and body weight (P < 0.001). There was no significant change in mean arterial blood pressure and pulse rate. Conclusions: Therapy with cilnidipine resulted in complete resolution of amlodipine-induced edema in all the cases without significant worsening of hypertension or tachycardia. Cilnidipine is an acceptable alternative antihypertensive for patients with amlodipine-induced edema. PMID:23378956

Shetty, Ranjan; Vivek, G; Naha, Kushal; Tumkur, Anil; Raj, Abhinav; Bairy, K L

2013-01-01

19

Role of neuroinflammation in hypertension-induced brain amyloid pathology.  

PubMed

Hypertension and sporadic Alzheimer's disease (AD) have been associated but clear pathophysiological links have not yet been demonstrated. Hypertension and AD share inflammation as a pathophysiological trait. Thus, we explored if modulating neuroinflammation could influence hypertension-induced ?-amyloid (A?) deposition. Possible interactions among hypertension, inflammation and A?-deposition were studied in hypertensive mice with transverse aortic coarctation (TAC). Given that brain A? deposits are detectable as early as 4 weeks after TAC, brain pathology was analyzed in 3-week TAC mice, before A? deposition, and at a later time (8-week TAC mice). Microglial activation and interleukin (IL)-1? upregulation were already found in 3-week TAC mice. At a later time, along with evident A? deposition, microglia was still activated. Finally, immune system stimulation (LPS) or inhibition (ibuprofen), strategies described to positively or negatively modulate neuroinflammation, differently affected A? deposition. We demonstrate that hypertension per se triggers neuroinflammation before A? deposition. The finding that only immune system activation, but not its inhibition, strongly reduced amyloid burden suggests that stimulating inflammation in the appropriate time window may represent a promising strategy to limit vascular-triggered AD-pathology. PMID:20961666

Carnevale, Daniela; Mascio, Giada; Ajmone-Cat, Maria Antonietta; D'Andrea, Ivana; Cifelli, Giuseppe; Madonna, Michele; Cocozza, Germana; Frati, Alessandro; Carullo, Pierluigi; Carnevale, Lorenzo; Alleva, Enrico; Branchi, Igor; Lembo, Giuseppe; Minghetti, Luisa

2012-01-01

20

Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension.  

PubMed

Pulmonary hypertension is characterised by a progressive increase in pulmonary arterial resistance due to endothelial and smooth muscle cell proliferation resulting in chronic obstruction of small pulmonary arteries. There is evidence that inflammatory mechanisms may contribute to the pathogenesis of human and experimental pulmonary hypertension. The aim of the study was to address the role of fractalkine (CX3CL1) in the inflammatory responses and pulmonary vascular remodelling of a monocrotaline-induced pulmonary hypertension model. The expression of CX3CL1 and its receptor CX3CR1 was studied in monocrotaline-induced pulmonary hypertension by means of immunohistochemistry and quantitative reverse-transcription PCR on laser-captured microdissected pulmonary arteries. It was demonstrated that CX3CL1 was expressed by inflammatory cells surrounding pulmonary arterial lesions and that smooth muscle cells from these vessels had increased CX3CR1 expression. It was then shown that cultured rat pulmonary artery smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but not migration of these cells. In conclusion, the current authors proposed that fractalkine may act as a growth factor for pulmonary artery smooth muscle cells. Chemokines may thus play a role in pulmonary artery remodelling. PMID:17182651

Perros, F; Dorfmüller, P; Souza, R; Durand-Gasselin, I; Godot, V; Capel, F; Adnot, S; Eddahibi, S; Mazmanian, M; Fadel, E; Hervé, P; Simonneau, G; Emilie, D; Humbert, M

2007-05-01

21

Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy  

Microsoft Academic Search

Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy.BackgroundType II diabetes in the Goto Kakizaki (GK) rats (derived from Wistar rats) is not associated with the development of obesity, hyperlipidemia, hypertension, or pronounced renal functional changes. The aim of this study was to investigate the effect of superimposed hypertension on renal function and morphology under conditions

Ulf Janssen; Stephen G. Riley; Athina Vassiliadou; Jürgen Floege; Aled O. Phillips

2003-01-01

22

Hypertension  

MedlinePLUS Videos and Cool Tools

... The cells of the body need oxygen and food to survive. Oxygen and nutrients are carried to ... develop high blood pressure. People who have a history of hypertension in the family or are African- ...

23

Phenylephrine-Induced Hypertension during Transient Middle Cerebral Artery Occlusion Alleviates Ischemic Brain Injury in Spontaneously Hypertensive Rats  

PubMed Central

Arterial hypertension is a major risk factor for ischemic stroke. However, the management of preexisting hypertension is still controversial in the treatment of acute stroke in hypertensive patients. The present study evaluates the influence of preserving hypertension during focal cerebral ischemia on stroke outcome in a rat model of chronic hypertension, the spontaneously hypertensive rats (SHR). Focal cerebral ischemia was induced by transient (1-hour) occlusion of the middle cerebral artery, during which mean arterial blood pressure was maintained at normotension (110-120 mmHg, group 1, n=6) or hypertension (160-170 mmHg, group 2, n=6) using phenylephrine. T2-, diffusion- and perfusion-weighted MRI were performed serially at five different time points: before and during ischemia, and at 1, 4 and 7 days after ischemia. Lesion volume and brain edema were estimated from apparent diffusion coefficient maps and T2-weighted images. Regional cerebral blood flow (rCBF) was measured within and outside the perfusion deficient lesion and in the corresponding regions of the contralesional hemisphere. Neurological deficits were evaluated after reperfusion. Infarct volume, edema, and neurological deficits were significantly reduced in group 2 versus group 1. In addition, higher values and rapid restoration of rCBF were observed in group 2, while rCBF in both hemispheres was significantly decreased in group 1. Maintaining preexisting hypertension alleviates ischemic brain injury in SHR by increasing collateral circulation to the ischemic region and allowing rapid restoration of rCBF. The data suggest that maintaining preexisting hypertension is a valuable approach to managing hypertensive patients suffering from acute ischemic stroke. PMID:22954904

Kang, Byeong-Teck; Leoni, Renata F.; Kim, Dong-Eog; Silva, Afonso C.

2012-01-01

24

Hypertension.  

PubMed

Hypertension is the most common modifiable risk factor for cardiovascular disease. Antihypertensive treatment substantially reduces the risk of heart failure, stroke, and myocardial infarction. Current guidelines recommend screening all adults for high blood pressure (BP). Lifestyle modifications to help control high BP include weight loss, exercise, moderation of alcohol intake, and a diet low in sodium and saturated fats and high in fruits and vegetables. Out-of-office BP monitoring should be used to confirm suspected white coat effect, especially in patients with apparent resistant hypertension. PMID:23402468

Winter, Katherine H; Tuttle, Laura A; Viera, Anthony J

2013-03-01

25

Prolonged attenuation of cold-induced hypertension by adenoviral delivery of renin antisense  

Microsoft Academic Search

Prolonged attenuation of cold-induced hypertension by adenoviral delivery of renin antisense.BackgroundRenin has been linked to the pathogenesis of some forms of hypertension, including cold-induced hypertension (CIH). Although several antihypertensive drugs that inhibit angiotensin-converting enzyme (ACE) and angiotensin II (Ang II) type 1 (AT1) receptors are available, they are short-lasting and have side effects. Inhibition of renin [the first and rate-limiting

XIUQING WANG; ZHONGJIE SUN; ROBERT CADE

2005-01-01

26

Hypertension  

Microsoft Academic Search

Hypertension is a forum for the presentation of scientific investigation of the highest quality in the broad field of cardiovascular regulation as it may affect high blood pressure research. The editors are interested in receiving original articles that deal with either basic or clinical research in the fields of biochemistry, cellular and molecular biology, immunology, physiology, pharmacology, and epidemiology. In

Allyn L. Mark; Francois M. Abboud; Gerald F. DiBona; Donald D. Heistad; Larry S. Tobacman; Victor J. Dzau; Carlos Ferrario; Eduardo Marban; Suzanne Oparil; Henry W. Overbeck; Stephen M. Schwartz; Karen Potvin Klein; Connie J. Nelson; John D. Baxter; Kathleen H. Berecek; Edward H. Blaine; Mordecai P. Blaustein; Barry M. Brenner; Michael J. Brody; Hans R. Brunner; Aram V. Chobanian; Robert J. Cody; Allen W. Cowley Jr.; Michael J. Dunn; Alvan R. Feinstein; D. Fink; S. Floras; Ronald H. Freeman; Edward D. Frohlich; Detlev Ganten; Haralambos P. Gavras; Celso E. Gomez-Sanchez; W. Gross; Oregon Willa Hsueh; Tadashi Inagami; I. Johnston; Stevo Julius; Norman M. Kaplan; Paul I. Korner; Theodore A. Kotchen; Eduardo M. Krieger; Brazil Kai Lau; Ronald M. Lauer; Jean-Francois Liard; Marshall D. Lindheimer; Friedrich C. Luft; Giuseppe Mancia; Harry S. Margolius; David A. McCarron; Oregon John; C. McGiff; Trefor O. Morgan; Michael J. Mulvany; Kazuo Murakami; Gary Nicholls; Michael J. Peach; Marc A. Pfeffer; V. Postnov; Morton P. Printz; John P. Rapp; John L. Reid; Donald J. Reis; J. Carlos Romero; E. Safar; A. Guillermo Scicli; T. Shepherd; Thomas Unger; Paul M. Vanhoutte; Stephen F. Vatner; Ronald G. Victor; B. Gunnar Wallin; Gordon H. Williams; Roger R. Williams; Vermont Margaret Foti; Mary Jane Jesse; Clyde E. Johnson; Ben G. Zimmerman

1992-01-01

27

Structure of Minimal Tetratricopeptide Repeat Domain Protein Tah1 Reveals Mechanism of Its Interaction with Pih1 and Hsp90*  

PubMed Central

Tah1 and Pih1 are novel Hsp90 interactors. Tah1 acts as a cofactor of Hsp90 to stabilize Pih1. In yeast, Hsp90, Tah1, and Pih1 were found to form a complex that is required for ribosomal RNA processing through their effect on box C/D small nucleolar ribonucleoprotein assembly. Tah1 is a minimal tetratricopeptide repeat protein of 111 amino acid residues that binds to the C terminus of the Hsp90 molecular chaperone, whereas Pih1 consists of 344 residues of unknown fold. The NMR structure of Tah1 has been solved, and this structure shows the presence of two tetratricopeptide repeat motifs followed by a C helix and an unstructured region. The binding of Tah1 to Hsp90 is mediated by the EEVD C-terminal residues of Hsp90, which bind to a positively charged channel formed by Tah1. Five highly conserved residues, which form a two-carboxylate clamp that tightly interacts with the ultimate Asp-0 residue of the bound peptide, are also present in Tah1. Tah1 was found to bind to the C terminus of Pih1 through the C helix and the unstructured region. The C terminus of Pih1 destabilizes the protein in vitro and in vivo, whereas the binding of Tah1 to Pih1 allows for the formation of a stable complex. Based on our data, a model for an Hsp90-Tah1-Pih1 ternary complex is proposed. PMID:22179618

Jimenez, Beatriz; Ugwu, Francisca; Zhao, Rongmin; Orti, Leticia; Makhnevych, Taras; Pineda-Lucena, Antonio; Houry, Walid A.

2012-01-01

28

Cirrhosis ameliorates monocrotaline-induced pulmonary hypertension in rats.  

PubMed

Common bile duct ligation (CBDL) induces biliary cirrhosis and pulmonary vasodilatation. We tested whether CBDL ameliorates monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Five groups of rats were studied: controls; rats dosed with MCT (60 mg.kg(-1) subcutaneously); CBDL; rats dosed with MCT followed by CBDL on day 7; and rats dosed with MCT followed by CBDL (day 7) and L-NAME therapy between days 24 and 28. 28-day survival was 26% in the MCT group and 72% in the MCT+CBDL group. Pulmonary vascular resistance measured on days 21 and 28 increased in the MCT and MCT+CBDL+L-NAME groups, but returned to normal in the MCT+CBDL group on day 28. Pulmonary artery (PA) medial hypertrophy persisted in MCT+CBDL rats. PA inflammation increased in MCT+CBDL rats, with accumulation of both intra- and perivascular macrophages. Exhaled nitric oxide (NO) levels decreased in the MCT group and increased in the MCT+CBDL group, which showed upregulation of inducible NO synthase and normal endothelial NO synthase. Blood endothelin (ET)-1 increased in CBDL, MCT, and MCT+CBDL rats. Levels of ET(B) receptors increased and ET(A) receptors decreased in the MCT+CBDL group, whereas the opposite changes occurred in the MCT group. Biliary cirrhosis induces pulmonary vasodilation that ameliorates MCT-induced PH and improves survival. Upregulation of inducible NO synthase and ET(B) receptor and downregulation of ET(A) receptor may be involved. PMID:19324959

Le Pavec, J; Perros, F; Eddahibi, S; Decante, B; Dorfmuller, P; Sitbon, O; Lebrec, D; Humbert, M; Mazmanian, M; Herve, P

2009-09-01

29

Hemin treatment abrogates monocrotaline-induced pulmonary hypertension.  

PubMed

Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 micromol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-alpha and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation. PMID:18991742

Shimzu, K; Takahashi, T; Iwasaki, T; Shimizu, H; Inoue, K; Morimatsu, H; Omori, E; Matsumi, M; Akagi, R; Morita, K

2008-11-01

30

Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension.  

PubMed

Hypertension in the elderly substantially contributes to cerebromicrovascular damage and promotes the development of vascular cognitive impairment. Despite the importance of the myogenic mechanism in cerebromicrovascular protection, it is not well understood how aging affects the functional adaptation of cerebral arteries to high blood pressure. Hypertension was induced in young (3 months) and aged (24 months) C57/BL6 mice by chronic infusion of angiotensin II (AngII). In young hypertensive mice, the range of cerebral blood flow autoregulation was extended to higher pressure values, and the pressure-induced tone of middle cerebral artery (MCA) was increased. In aged hypertensive mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In young mice, the mechanism of adaptation to hypertension involved upregulation of the 20-HETE (20-hydroxy-5,8,11,14-eicosatetraenoic acid)/transient receptor potential cation channel, subfamily C (TRPC6) pathway and this mechanism was impaired in aged hypertensive mice. Downstream consequences of cerebrovascular autoregulatory dysfunction in aged AngII-induced hypertensive mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal dependent cognitive function. Collectively, aging impairs autoregulatory protection in the brain of mice with AngII-induced hypertension, potentially exacerbating cerebromicrovascular injury and neuroinflammation. PMID:23942363

Toth, Peter; Tucsek, Zsuzsanna; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Tarantini, Stefano; Deak, Ferenc; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-11-01

31

Reversal of impaired calcium homeostasis in the rat diaphragm subjected to Monocrotaline–induced pulmonary hypertension  

Microsoft Academic Search

Monocrotaline (MCT) pneumotoxicity is known to alter the structure of pulmonary vascular wall and impairs endothelial cell function resulting in pulmonary hypertension. Its effect on the diaphragm muscle has not yet been elucidated. This study examines the effect of MCT pneumotoxicity on calcium transport in the rat diaphragm. Pulmonary hypertension induced by MCT pneumotoxicity caused a significant increase (P<0.001) in

N. A. Kanj; M. G. Nasser; W. A. Medawar; A. U. Al Tayeh; M. Y. Khoury; C. F. Nassar

1999-01-01

32

Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex  

PubMed Central

Summary The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs), RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N) in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 phosphopeptide complex reveals a highly specific phosphopeptide recognition mechanism in which Lys57 and 64 in PIH1D1, along with a conserved DpSDD phosphopeptide motif within TEL2, are essential and sufficient for binding. Proteomic analysis of PIH1D1 interactors identified R2TP complex substrates that are recruited by the PIH-N domain in a sequence-specific and phosphorylation-dependent manner suggestive of a common mechanism of substrate recognition. We propose that protein complexes assembled by the R2TP complex are defined by phosphorylation of a specific motif and recognition by the PIH1D1 subunit. PMID:24656813

Ho?ejší, Zuzana; Stach, Lasse; Flower, Thomas G.; Joshi, Dhira; Flynn, Helen; Skehel, J. Mark; O’Reilly, Nicola J.; Ogrodowicz, Roksana W.; Smerdon, Stephen J.; Boulton, Simon J.

2014-01-01

33

Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension  

Microsoft Academic Search

Pulmonary hypertension is characterised by a progressive increase in pulmonary arterial resistance due to endothelial and smooth muscle cell proliferation resulting in chronic obstruction of small pulmonary arteries. There is evidence that inflammatory mechanisms may contribute to the pathogenesis of human and experimental pulmonary hypertension. The aim of the study was to address the role of fractalkine (CX3CL1) in the

F. Perros; P. Dorfmuller; R. Souza; I. Durand-Gasselin; V. Godot; F. Capel; S. Adnot; S. Eddahibi; M. Mazmanian; E. Fadel; P. Herve; G. Simonneau; D. Emilie; M. Humbert

2007-01-01

34

Neural-Renal Interactions in the Hypertension Induced by Papillary Necrosis: Role of Dietary Salt Intake  

Microsoft Academic Search

The effects of high salt intake (1.0% NaCl in the drinking water) on rats made hypertensive by 2-bromoethylamine hydrobromide (BEA) treatment (200 mg\\/kg, i.p.) were examined. BEA-induced medullary necrosis resulted in a mild hypertension (146 ± 5 mm Hg) that was exacerbated by 4 weeks of high salt intake (163 ± 6 mmHg). BEA-treated rats had significant salt-induced increases in

David R. Wallace

1990-01-01

35

Oral taurine supplementation prevents fructose-induced hypertension in rats.  

PubMed

Taurine is known to have antihypertensive and lipid-lowering effects in some experimental models and patients. On the other hand, intracellular free calcium and magnesium play important roles in regulating the tonus of blood vessels and insulin sensitivity. We examined the effect of oral taurine supplementation on blood pressure, serum metabolic parameters, and platelet cytosolic free calcium ([Ca(2+)](i)) and magnesium ([Mg(2+)](i)) concentration in fructose-fed Sprague-Dawley rats. Systolic blood pressure and platelet [Ca(2+)](i) were significantly higher in rats fed a 60% fructose diet. Oral taurine supplementation (1% in drinking water) completely prevented the elevation of blood pressure and an increase in platelet [Ca(2+)](i), but exacerbated hyperinsulinemia, hypertriglyceridemia, and a decrease in platelet [Mg(2+)](i). In conclusion, taurine may ameliorate fructose-induced hypertension in rats by preventing an increase in intracellular free calcium concentration. The blood pressure-lowering effect of taurine appeared to be independent from its effect on glucose and lipid metabolism in this model. PMID:15168061

Harada, Hisashi; Tsujino, Takeshi; Watari, Yasuhiro; Nonaka, Hidemi; Emoto, Noriaki; Yokoyama, Mitsuhiro

2004-05-01

36

Pravastatin attenuates hypertension, oxidative stress and angiogenic imbalance in rat model of placental ischemia-induced hypertension  

PubMed Central

Preeclampsia is a pregnancy-specific condition characterized by an imbalance of circulating angiogenic factors and new-onset hypertension. Although current treatment options are limited, recent studies suggest pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin would restore angiogenic balance and reduce mean arterial pressure (MAP) in rats with reduced utero-placental perfusion pressure (RUPP)-induced hypertension. Pravastatin was administered i.p. (1 mg/kg/day) in RUPP (RUPP+P) and normal pregnant rats (NP+P) from day 14-19 of pregnancy. On day 19, MAP was measured via catheter, conceptus data was recorded and tissues collected. MAP was increased (p<0.05) in RUPP compared to NP dams and pravastatin ameliorated this difference. Pravastatin attenuated decreased fetal weight and plasma VEGF and the RUPP-induced increased sFlt-1 when compared to NP dams. Pravastatin treatment did not improve angiogenic potential in RUPP serum and decreased (P<0.05) endothelial tube formation in NP rats. RUPP rats presented with indices of oxidative stress such as increased placental catalase activity and plasma TBARS along with decreased plasma total antioxidant capacity compared to NP controls and pravastatin attenuated these effects. MAP, fetal weight, plasma VEGF, and plasma sFlt-1 were unchanged in NP+P compared to NP controls. The present data indicate that treatment with pravastatin attenuates oxidative stress and lowers MAP in placental ischemia-induced hypertension, but may have negative effects on circulating angiogenic potential during pregnancy. Further studies are needed to determine if there are long-term deleterious effects on maternal or fetal health following pravastatin treatment during pregnancy-induced hypertension or preeclampsia. PMID:23460290

Bauer, Ashley J; Banek, Christopher T; Needham, Karen; Gillham, Haley; Capoccia, Susan; Regal, Jean F; Gilbert, Jeffrey S

2013-01-01

37

Captopril-induced changes in effective renal plasma flow in hypertensive renal transplant recipients.  

PubMed

The role of converting enzyme inhibitor enhanced radionuclide investigations in post-transplant hypertension is not clearly defined. Presence of renal failure, chronic rejection and use of cyclosporin A complicates the results. Captopril-induced changes in effective renal plasma flow (ERPF) were studied in 10 patients with severe post-transplant hypertension and no evidence of rejection. Angiographic correlation was available in all. Six patients had a significant increase in ERPF after captopril, and all had a negative angiogram. One patient on CsA with a negative angiogram had no change in ERPF. Three patients had a fall in ERPF, and all 3 had transplant renal artery stenosis. Captopril-induced changes in ERPF can differentiate patients with native-kidney-induced hypertension from those with hypertension secondary to transplant renal artery stenosis in patients without evidence of rejection. PMID:8884105

Sud, K; Oomen, R; Jacob, C K; Shastry, J C

1996-08-01

38

Apelin-induced hemorheological alterations in DOCA-salt hypertensive rats.  

PubMed

Apelin is a hypotensive peptide. Red blood cell (RBC) deformability and aggregation were previously demonstrated to be altered in various hypertension (HT) models. In the present study, we investigated possible alterations in RBC deformability and aggregation in response to apelin in DOCA-salt hypertensive rats. Rats were randomly divided into 4 groups: Control (C), Hypertension (HT), Apelin, and Apelin + Hypertension (Apelin + HT). HT was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly for 4 weeks, whereas apelin was administered (200 ?g/kg i.p.) for 17 days. RBC deformability and aggregation were determined using an ektacytometer. Blood pressure was monitored using a tail cuff system. Systolic blood pressure was decreased in the Apelin and Apelin + HT groups and increased in the HT group. RBC deformability was not significantly altered in the HT group. Apelin administration induced a statistically significant increase in RBC deformability in control animals, whereas erythrocytic deformability in the Apelin + HT group was decreased compared to the Apelin group. RBC aggregation of hypertensive animals was reduced compared to controls. Apelin administration induced increased RBC aggregation in hypertensive rats. Our results showed favorable effects of apelin on RBC deformability in control animals, but not in hypertensive rats. PMID:23302598

Kursunluoglu-Akcilar, Raziye; Kilic-Toprak, Emine; Kilic-Erkek, Ozgen; Turgut, Sebahat; Bor-Kucukatay, Melek

2014-01-01

39

Mechanics of Atherosclerosis, Hypertension Induced Growth, and Arterial Remodeling  

E-print Network

stress, in response to hemodynamic loads. Using an aortic coarctation model of hypertension, we found structural arterial responses differ in the aorta, coronary and cerebral arteries. Effects of elevated pressure manifest first in the central arteries...

Hayenga, Heather Naomi

2012-07-16

40

A novel adipocytokine, omentin, inhibits monocrotaline-induced pulmonary arterial hypertension in rats.  

PubMed

Omentin is a novel adipocytokine mainly expressed in visceral rather than subcutaneous adipose tissue. Several epidemiological studies demonstrated the negative relationship between blood omentin level and occurrence of obesity, type 2 diabetes and hypertension. Increases of inflammatory responses, contractile reactivity and structural remodeling of vascular wall contribute to hypertension development. Our in vitro studies previously demonstrated that omentin inhibited those hypertension-related pathological processes. In addition, our in vivo study demonstrated that intravenously injected omentin acutely inhibited agonists-induced increases of blood pressure in rats. However, the chronic effects of omentin on hypertension development are not determined. In the present study, we tested the hypothesis that chronic omentin treatment may inhibit pulmonary arterial (PA) hypertension (PAH). PAH was induced by a single intraperitoneal injection of monocrotaline (MCT: 60 mg/kg) to rats. Omentin (18 ?g/kg/day) was intraperitoneally treated for 14 days. Chronic omentin treatment inhibited MCT-induced increases in PA pressure. Omentin inhibited MCT-induced right ventricular hypertrophy as well as increase of lung to body weight ratio. Histologically, omentin inhibited MCT-induced PA hyperplasia. Further, omentin inhibited the impairment of both endothelium-dependent and -independent relaxations mediated by acetylcholine and sodium nitroprusside, respectively. In conclusion, we for the first time demonstrate that chronic omentin treatment inhibits MCT-induced PAH in rats via inhibiting vascular structural remodeling and abnormal contractile reactivity. PMID:25152392

Kazama, Kyosuke; Okada, Muneyoshi; Yamawaki, Hideyuki

2014-09-12

41

Role of the sympathetic nervous system during the development of obesity-induced hypertension in rabbits  

Microsoft Academic Search

We have previously reported that weight gain induced by high-fat diet (HFD) leads to an increase in mean arterial pressure (MAP, +14%) and heart rate (HR, +31%) in the adult rabbit. In the present study, we tested the hypothesis that an increased activity of the sympathetic nervous system may contribute to the development of obesity-induced hypertension. A combination of ?-

Vladan Antic; Francesca Kiener-Belforti; Aldo Tempini; Bruce N. Van Vliet; Jean-Pierre Montani

2000-01-01

42

Maternal Obesity and Energy Intake as Risk Factors of Pregnancy-induced Hypertension among Iranian Women  

PubMed Central

ABSTRACT Pregnancy-induced hypertension is causing striking maternal, foetal and neonatal mortality and morbidity in the world. A case-control study was conducted on 113 women with gestational hypertension and 150 healthy pregnant women at Shahid Akbarabadi Hospital of obstetrics and gynaecology in south of Tehran. Women who were obese (OR 4.44; 95% CI 1.84-10.72) before pregnancy were more likely to develop gestational hypertension. Proportion of having excessive gestational weight gain was positively and significantly associated with development of gestational hypertension (OR 2.70; 95% CI 1.19-6.13). Furthermore, findings revealed that women who were in the highest quartile of mid-arm-circumference had a 3-fold increased risk of gestational hypertension compared to women in the lowest quartile (OR 8.93; 95% CI 2.16-36.93). We found that having been in the highest quartile of energy intake positively correlated with increased risk of gestational hypertension (OR 9.66; 95% CI 3.30-28.21). The results suggest pre-pregnancy obesity, excessive gestational weight gain, and increased intake of energy as potential risk factors of developing gestational hypertension.

Kazemian, Elham; Dorosty-Motlagh, Ahmad Reza; Eshraghian, Mohammad Reza; Bagheri, Minoo

2014-01-01

43

CaMK4 Gene Deletion Induces Hypertension  

PubMed Central

Background The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which suggests a role for this kinase in the regulation of vascular tone. Methods and Results To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4?/? mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. (J Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.) PMID:23130158

Santulli, Gaetano; Cipolletta, Ersilia; Sorriento, Daniela; Del Giudice, Carmine; Anastasio, Antonio; Monaco, Sara; Maione, Angela Serena; Condorelli, Gianluigi; Puca, Annibale; Trimarco, Bruno; Illario, Maddalena; Iaccarino, Guido

2012-01-01

44

The role of the sympathetic nervous system in oestrogen-induced hypertension in rats.  

PubMed Central

Albino rats of either sex received chronic ethinyl oestradiol (EO) treatment (1.5 mg kg-1 daily, i.m.) for 3 weeks. Untreated control rats received arachis oil vehicle alone. Chronic EO treatment resulted in elevation of blood pressure in both sexes. Female rats exhibited significantly greater elevation in blood pressure than males. In chronic EO-treated rats pressor responses to low doses (0.5 micrograms kg-1) of noradrenaline were significantly increased, while those to angiotensin II, acetylcholine and isoprenaline were unaltered. Chronic EO treatment also sensitized the vascular bed of the rats' hindquarters to noradrenaline. EO-induced hypertension was associated with significant increase in dopamine-beta-hydroxylase activity of adrenal glands. Complete bilateral adrenalectomy or chemical sympathectomy prevented the development of EO-induced hypertension. It is suggested that chronic treatment of rats with EO induces and maintains hypertension. The peripheral sympathetic system plays an important role in this phenomenon. PMID:3814904

Bhatt, J. D.; Gulati, O. D.

1986-01-01

45

Rosuvastatin, sildenafil and their combination in monocrotaline-induced pulmonary hypertension in rat.  

PubMed

Abstract There is considerable interest in the pleiotropic effects of statins and their potential role in the treatment of pulmonary hypertension. Previous experimental findings indicate that a combination of lipophilic statins with phosphodiesterase type-5 inhibitor, sildenafil, can offer preventive effects on rat monocrotaline-induced pulmonary hypertension. The present study is aimed to assess whether therapeutic regimen provides any benefits. Seven days after pulmonary hypertension induction, hydrophilic rosuvastatin and sildenafil were given for 14 days to male Wistar outbred rats. Right ventricular pressure, right ventricle mass and three biomarkers were evaluated after 21 days: brain natriuretic peptide, high-density lipoprotein cholesterol and vascular endothelial growth factor. The present study demonstrates that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure. The results of biochemical measurements may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development. PMID:25296680

Jasi?ska-Stroschein, Magdalena; Owczarek, Jacek; Weso?owska, Anna; Orszulak-Michalak, Daria

2014-09-01

46

Exercise training attenuates placental ischemia induced hypertension and angiogenic imbalance in the rat  

PubMed Central

An imbalance between pro-angiogenic (vascular endothelial growth factor, VEGF) and anti-angiogenic (soluble fms-like tyrosine kinase-1, sFlt-1) factors plays an important role in hypertension associated with reduced utero-placental perfusion (RUPP). Exercise has been shown to stimulate pro-angiogenic factors such as VEGF in both the pregnant and non-pregnant state, thus we hypothesized exercise training would attenuate both angiogenic imbalance and hypertension due to RUPP. Four groups of animals were studied: RUPP and normal pregnant (NP) controls and NP and RUPP + exercise training (NP or RUPP+EX). Exercise training attenuated RUPP-induced: hypertension (P<0.05); increased sFlt-1(P<0.05); decreased VEGF (P<0.05), and elevated sFlt-1:VEGF ratio. The positive effects of exercise on angiogenic balance in the RUPP rats were confirmed by restoration (P<0.05) of the RUPP-induced decrease in endothelial tube formation in HUVECs treated with serum from each of the experimental groups. Placental prolyl hydroxylase-1 (PHD1) was increased (P<0.05) in RUPP+Ex rats. Decreased trolox equivalent antioxidant capacity in the placenta, amniotic fluid and kidney of the RUPP rats was reversed by exercise. RUPP induced increase in renal TBARS was attenuated by exercise. The present data show exercise training before and during pregnancy attenuates placental ischemia-induced hypertension, angiogenic imbalance and oxidative stress in the RUPP rat and reveals that increased PHD1 is associated with decreased sFlt-1 thus revealing several potential pathways for exercise training to mitigate the effects of placental ischemia-induced hypertension. Lastly, the present study demonstrates exercise training may be a useful approach to attenuate the development of placental ischemia-induced hypertension during pregnancy. PMID:23090773

Gilbert, Jeffrey S; Banek, Christopher T; Bauer, Ashley J; Gingery, Anne; Needham, Karen

2013-01-01

47

TJ0711, a novel vasodilatory ?-blocker, protects SHR rats against hypertension induced renal injury  

PubMed Central

Previous studies suggested that ?-blockers with adjunctive ?1-blocking activities warrant renoprotective function other than the therapeutic effect on hypertension. The current report is designed to dissect the role of TJ0711, a novel ?-blocker with a 1:1 ratio for the ?1/?1 blocking activities, in renoprotection in SHR rats. It was noted that TJ0711 possesses similar potency for control of blood pressure as that of Carvedilol. However, TJ0711 is much more potent in terms of protecting SHR rats against hypertension induced renal injury. Specifically, SHR rats treated with 20mg/kg/day of TJ0711 manifested significantly lower levels for urine albumin and total protein. In line with these result, TJ0711 treated rats displayed much less severe pathological changes in the kidneys. Mechanistic studies revealed that TJ0711 improves kidney perfusion during the course of hypertensive insult by enhancing eNOS expression through suppressing inflammatory cytokine secretion. TJ0711 also attenuates Vasohibin-1 expression to prevent HIF-1? from signal-induced degradation, and by which it promotes HO-1 expression to protect SHR rats against oxidative stress induced by hypertension in the kidneys. Together, our data suggest that TJ0711 possesses higher potency for renoprotection while manifesting the similar effect on hypertension therapy as Carvedilol. PMID:23634239

Yang, Juan; Ning, Yong; Qiu, Jun; He, Jin-Seng; Li, Wei; Ma, Zu-Fu; Shao, Ju-Fang; LI, Yue-Qiang; Zeng, Rui; Zhang, Meng; Cheng, Jia; Chen, Su-Fang; Xu, Gang; Wang, Cong-Yi; Yao, Ying

2013-01-01

48

Vascular Endothelial Growth Factor Inhibitor-Induced Hypertension: Basics for Primary Care Providers  

PubMed Central

Frequently, primary care providers continue to manage the overall medical care of cancer patients. With newer and often more potent antitumor agents, patients may present to their local physicians with drug-induced toxicities such as hypertension induced by vascular endothelial growth factor (VEGF) inhibitors. It is imperative that these healthcare providers are aware of basic aspects of this drug class, as its use has increased significantly in the last several years. Uncontrolled or malignant hypertension due to these agents should be recognized readily and treated early to prevent more severe outcomes. This overview provides a brief background on the role of VEGF and angiogenesis in tumor metabolism as well as theories of the mechanism of VEGF inhibitors and hypertension. Helpful clinical practice aspects including the types of inhibitors used in the United States and their pharmacologic characteristics will be discussed. Also, diagnosis and treatment of hypertension induced by vascular endothelial growth factors are reviewed. A summary of key aspects of this drug class and hypertension is included. PMID:21629798

Escalante, Carmen P.; Zalpour, Ali

2011-01-01

49

Evidence against a role for inducible nitric oxide synthase in the hyperdynamic circulation of portal-hypertensive rats  

Microsoft Academic Search

Background\\/Aims Excessive nitric oxide biosynthesis caused by expression of inducible NO synthase has been implicated in the hyperdynamic circulation of portal hypertension. The aim of the study was to investigate whether inducible NO synthase is expressed in portal hypertension and accounts for the hyperdynamic circulation. Methods In study 1, NO synthase activities were measured by the conversion of l-arginine to

Mercedes Fernández; Juan Carlos García-Pagán; Maria Casadevall; Cristina Bernadich; Carlos Piera; Brendan J. R. Whittle; Josep M. Piqué; Jaume Bosch; Juan Rodés

1995-01-01

50

Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application.  

PubMed

We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility, which causes pulmonary gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n = 7), the priming solution was preheated (42-46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35-44 mm?Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiologic range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for cancer treatment. PMID:23820278

Ballard-Croft, Cherry; Wang, Dongfang; Jones, Cameron; Wang, Jingkun; Pollock, Robert; Jubak, Bob; Topaz, Stephen; Zwischenberger, Joseph B

2013-01-01

51

INTERLEUKIN 17 PROMOTES ANGIOTENSIN II-INDUCED HYPERTENSION AND VASCULAR DYSFUNCTION  

PubMed Central

We have previously shown that T cells are required for the full development of angiotensin II-induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. Th17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL17). We found that angiotensin II infusion increased IL17 production from T cells and IL17 protein in the aortic media. To determine the effect of IL17 on blood pressure and vascular function, we studied IL17?/? mice. The initial hypertensive response to angiotensin II infusion was similar in IL17?/? and C57BL/6J mice. However, hypertension was not sustained in IL17?/? mice, reaching levels 30 mmHg lower than in wild type mice by 4 weeks of angiotensin II infusion. Vessels from IL17?/? mice displayed preserved vascular function, decreased superoxide production, and reduced aortic T cell infiltration in response to angiotensin II. Gene array analysis on cultured human aortic smooth muscle cells revealed that IL17, in conjunction with tumor necrosis factor ?, modulated expression of over 30 genes, including a number of inflammatory cytokines/chemokines. Examination of IL17 in diabetic humans showed that serum levels of this cytokine were significantly increased in those with hypertension compared to normotensive subjects. We conclude that IL17 is critical for the maintenance of angiotensin II-induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease. PMID:20038749

Madhur, Meena S.; Lob, Heinrich E.; McCann, Louise A.; Iwakura, Yoichiro; Blinder, Yelena; Guzik, Tomasz J.; Harrison, David G.

2010-01-01

52

The effect of topical diltiazem on ocular hypertension induced by water loading in rabbits  

Microsoft Academic Search

The aim of this work was to assess the effect of topical diltiazem on the ocular hypertension induced by water loading in rabbits. The effect of three different concentrations of diltiazem on the intraocular pressure rise produced by oral administration of tap water (60 ml\\/kg) was tested in groups of nine or ten rabbits each. When applied at the lowest

Juan Santafé; Mar??a Jesús Mart??nez de Ibarreta; José Segarra; José Melena

1999-01-01

53

Overfeeding-Induced Obesity in Spontaneously Hypertensive Rats: An Animal Model of the Human Metabolic Syndrome  

Microsoft Academic Search

Background\\/Aims: The metabolic syndrome (MS) has become an epidemiological problem in Western countries. We developed a diet-induced obese rat model that mimics all the symptoms of MS in humans, but whose insulin resistance, hyperphagia and hyperleptinemia are caused by nutrition rather than genetic modifications. Methods: Spontaneously hypertensive rats (SHR) were allowed for 12 weeks to choose between a cafeteria diet

Anja Miesel; Helge Müller; Margot Thermann; Marc Heidbreder; Peter Dominiak; Walter Raasch

2010-01-01

54

The Role of NADPH Oxidase in Chronic Intermittent Hypoxia-Induced Pulmonary Hypertension in Mice  

PubMed Central

Obstructive sleep apnea, characterized by intermittent periods of hypoxemia, is an independent risk factor for the development of pulmonary hypertension. However, the exact mechanisms of this disorder remain to be defined. Enhanced NADPH oxidase expression and superoxide (O2?·) generation in the pulmonary vasculature play a critical role in hypoxia-induced pulmonary hypertension. Therefore, the current study explores the hypothesis that chronic intermittent hypoxia (CIH) causes pulmonary hypertension, in part, by increasing NADPH oxidase–derived reactive oxygen species (ROS) that contribute to pulmonary vascular remodeling and hypertension. To test this hypothesis, male C57Bl/6 mice and gp91phox knockout mice were exposed to CIH for 8 hours per day, 5 days per week for 8 weeks. CIH mice were placed in a chamber where the oxygen concentration was cycled between 21% and 10% O2 45 times per hour. Exposure to CIH for 8 weeks increased right ventricular systolic pressure (RVSP), right ventricle (RV):left ventricle (LV) + septum (S) weight ratio, an index of RV hypertrophy, and thickness of the right ventricular anterior wall as measured by echocardiography. CIH exposure also caused pulmonary vascular remodeling as demonstrated by increased muscularization of the distal pulmonary vasculature. CIH-induced pulmonary hypertension was associated with increased lung levels of the NADPH oxidase subunits, Nox4 and p22phox, as well as increased activity of platelet-derived growth factor receptor ? and its associated downstream effector, Akt kinase. These CIH-induced derangements were attenuated in similarly treated gp91phox knockout mice. These findings demonstrate that NADPH oxidase–derived ROS contribute to the development of pulmonary vascular remodeling and hypertension caused by CIH. PMID:18952568

Nisbet, Rachel E.; Graves, Anitra S.; Kleinhenz, Dean J.; Rupnow, Heidi L.; Reed, Alana L.; Fan, Tai-Hwang M.; Mitchell, Patrick O.; Sutliff, Roy L.; Hart, C. Michael

2009-01-01

55

Antioxidant Effects of Bovine Lactoferrin on Dexamethasone-Induced Hypertension in Rat  

PubMed Central

Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30??g/kg/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300?mg/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF. PMID:24587916

Safaeian, Leila; Zabolian, Hadi

2014-01-01

56

Use of labetalol and methyldopa in pregnancy-induced hypertension.  

PubMed Central

1 Nineteen pregnant patients whose mean arterial pressure (MAP) was persistently greater than or equal to 103.3 mmHg were given labetalol or methyldopa. 2 Singificant falls (P less than 0.001) in BP only occurred in the group treated with labetalol, and daily BP control was better in this group. 3 Two severely hypertensive patients were successfully treated with intravenous labetalol. 4 There was a higher incidence of spontaneous labour in the labetalol group and a significant difference (P less than 0.05) in the Bishop score of the cervix between the two groups. 5 There were no apparent detrimental effects on the foetus antenatally, during labour or post partum. 6 Slight breathlessness in one patient treated with labetalol was the only side-effect observed but drowsiness, headache and postural hypotension were reported in patients receiving methyldopa. PMID:526404

Lamming, G D; Symonds, E B

1979-01-01

57

Fine Structural Alterations of Bovine Peripheral Pulmonary Arteries in Hypoxia-Induced Hypertension  

PubMed Central

Cellular alterations of the distal bovine pulmonary arteries in hypoxia-induced pulmonary hypertension were studied. These lesions were related to pulmonary hemodynamic changes and contrasted to the cellular response observed in hyperkinetic pulmonary and systemic hypertension as well as other forms of vascular injury. Medial thickening and mild adventitial proliferation with an absence of intimal proliferative lesions related to a progressive increase in mean pulmonary arterial pressure and pulmonary vascular resistance were observed. Smooth muscle and endothelial cells exhibited distinct degenerative alterations in response to the maintained hypertensive state resulting from the lowered alveolar oxygen tension. ImagesFig 5Fig 6Fig 7Fig 14Fig 15Fig 16Fig 8Fig 9Fig 10Fig 17Fig 18Fig 19Fig 20Fig 21Fig 1Fig 2Fig 3Fig 4Fig 11Fig 12Fig 13 PMID:4357176

Jaenke, Roger S.; Alexander, Archibald F.

1973-01-01

58

76 FR 76432 - Notice of Proposed Information for Public Comment for: Capture Energy Efficiency Measures for PIH  

Federal Register 2010, 2011, 2012, 2013

The proposed information collection requirement described below will be submitted to the Office of Management and Budget (OMB) for review, as required by the Paperwork Reduction Act. The Department is soliciting public comments on the subject proposal. HUD is creating the Capture Energy Efficiency Measures for PIH (CEEMP) data system to track the amount and types of Energy Conservation Measures......

2011-12-07

59

Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH).  

PubMed

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adrenals, and systemic endocrine parameters were studied in ISIAH of different ages and compared to normotensive Wistar albino Glaxo (WAG) rats. Native organs were obtained for Western and PCR analysis. Perfusion-fixed organs were prepared for histopathology and quantitative histochemistry. Plasma renin and adrenal hormones were measured. Renal morphology was unaltered in ISIAH. The hypothalamic-pituitary-adrenocortical (HPA) axis was constitutively upregulated with enlarged adrenal cortices and enhanced plasma corticosterone levels. Plasma renin activity was not different between groups, whereas aldosterone levels were in part reduced. Juxtaglomerular NO synthase type 1, cyclooxygenase type 2, and renin expression were significantly reduced, whereas tubular gene products related to sodium transport (bumetanide-sensitive Na, K, 2Cl cotransporter type 2; thiazide-sensitive Na, Cl cotransporter; epithelial Na channel-alpha; 11beta-hydroxysteroid dehydrogenase type 2) were increased. These data suggest enhanced volume conservation by the kidney. Our data define ISIAH as an attractive model for the renal components determining salt and water homeostasis in hypertension. The specific condition of a basally stimulated HPA axis is highlighted, including the option to study effects superimposed by emotional stress. PMID:16341522

Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning; Maslova, Larissa; Ivanova, Ludmila; Jensen, Boye; Markel, Arkady L; Bachmann, Sebastian

2006-06-01

60

Nifedipine-induced histological changes in the parotid glands of hypertensive rats.  

PubMed

Nifedipine is a widely used anti-anginal and anti-hypertensive agent. It is associated with significant gingival changes attributed more to collagen hyperplasia than to enhancement of protein synthesis. We investigated the influence of nifedipine on morphological changes in the parotid glands of rats in a model of hypertension. Twenty-eight male Wistar rats (8-10 weeks; 200±15 g) were divided into four groups (A-D). Hypertension was induced by surgical means in groups C and D. Animals in groups B and D were treated with nifedipine (0.85 mg/kg) via a gastroesophageal catheter the day after surgery (experimental day-1) for 2 weeks. A significant difference was observed between the control group and nifedipine group and between the control group and hypertension group with regard to the weight of the parotid gland and its surface area. Histological findings demonstrated changes in the parotid glands of hypertensive animals with mild vessel dilatation and infiltration of inflammatory cells. These histological findings seemed to be due more to changes in venous function than to alterations in gland architecture. PMID:24918367

Seferos, Nikos; Daskala, Ioanna; Kotsiou, Antonia; Tsamouri, Madeleine; Tesseromatis, Christine

2014-01-01

61

The time course of salt-induced hypertension, and why it matters.  

PubMed

The epidemiology of salt-induced hypertension has been explored in detail in animal studies, in some cases involving exposures to excess dietary salt for much of the animal's lifespan. The results of these studies demonstrate the presence of two distinct time courses of the blood pressure response to a high salt intake: an acute (rapid) blood pressure response occurring over days to weeks, and a slow and progressive blood pressure response that develops over extremely long periods of time, amounting to a significant fraction of the lifespan in normal individuals. The acute form of salt sensitivity is well known in humans, having often been demonstrated as a fall in blood pressure during the period of salt restriction. The slow and progressive form of salt sensitivity has been demonstrated directly in rats and chimpanzees and is also evident in analyses of human cross-population data as a salt dependency of age-associated changes of blood pressure. This slow and progressive component of salt-induced hypertension may be attributable, at least in part, to a progressive rise in the acute salt sensitivity of blood pressure during sustained exposure to high salt. However, a progressively irreversible or 'self sustaining' component of salt-induced hypertension has also been demonstrated in rat studies. This irreversible component has not been completely characterized, but its presence raises the possibility that blood pressure responses to salt restriction may not fully reveal the contribution of salt to blood pressure or the epidemiology of hypertension. These various components of salt sensitivity (acute vs slow, reversible vs irreversible) should be considered in any comprehensive explanation of the effects of salt on blood pressure and especially in experimental studies of the genetic and physiological mechanisms underlying salt-induced hypertension. PMID:19079278

Van Vliet, B N; Montani, J-P

2008-12-01

62

Fetal pulmonary hypertension prolongs the endothelin-1 induced increase in pulmonary artery smooth muscle cell cytosolic calcium concentration  

Microsoft Academic Search

Introduction: At birth, pulmonary artery (PA) blood flow increases 8–10 fold and PA pressure falls by 50% within 24 hours. The mechanisms responsible for postnatal adaptation of the pulmonary circulation remain incompletely understood. High serum endothelin-1 (ET-1) levels are found in infants with persistent pulmonary hypertension of the newborn. We hypothesized that chronic intrauterine pulmonary hypertension (PHT) potentiates agonist induced

B. C. Linden; F. O. Anderson; E. R. Resnik; J. M. Herron; D. N. Cornfield

2003-01-01

63

Complement activation is critical for placental ischemia-induced hypertension in the rat.  

PubMed

Preeclampsia is a major obstetric problem defined by new-onset hypertension and proteinuria associated with compromised placental perfusion. Although activation of the complement system is increased in preeclampsia compared to normal pregnancy, it remains unclear whether excess complement activation is a cause or consequence of placental ischemia. Therefore, we hypothesized that complement activation is critical for placental ischemia-induced hypertension. We employed the reduced utero-placental perfusion pressure (RUPP) model of placental ischemia in the rat to induce hypertension in the third trimester and evaluated the effect of inhibiting complement activation with a soluble recombinant form of an endogenous complement regulator, human complement receptor 1 (sCR1; CDX-1135). On day 14 of a 21-day gestation, rats received either RUPP or Sham surgery and 15 mg/kg/day sCR1 or saline intravenously on days 14-18. Circulating complement component 3 decreased and complement activation product C3a increased in RUPP vs. Sham (p<0.05), indicating complement activation had occurred. Mean arterial pressure (MAP) measured on day 19 increased in RUPP vs. Sham rats (109.8±2.8 mmHg vs. 93.6±1.6 mmHg). Treatment with sCR1 significantly reduced elevated MAP in RUPP rats (98.4±3.6 mmHg, p<0.05) and reduced C3a production. Vascular endothelial growth factor (VEGF) decreased in RUPP compared to Sham rats, and the decrease in VEGF was not affected by sCR1 treatment. Thus, these studies have identified a mechanistic link between complement activation and the pregnancy complication of hypertension apart from free plasma VEGF and have identified complement inhibition as a potential treatment strategy for placental ischemia-induced hypertension in preeclampsia. PMID:23685261

Lillegard, Kathryn E; Johnson, Alex C; Lojovich, Sarah J; Bauer, Ashley J; Marsh, Henry C; Gilbert, Jeffrey S; Regal, Jean F

2013-11-01

64

Effect of gender in centrally induced angiotensin II hypertension in dogs.  

PubMed

This study was designed to investigate the relation between gender, an endogenous inhibitor of the Na+-K+ pump, and volume-dependent hypertension induced by stimulation of the brain renin-angiotensin system and increased salt intake. Angiotensin II (20 ng/min i.c.v.) was infused for 4 weeks in five dogs of each sex with saline as the drinking fluid. In male dogs, angiotensin II induced parallel pressor (30%) and dipsogenic responses (70%), whereas no hypertension and no increase in fluid intake were observed in females. In contrast, the activity of the Na+-K+ pump as assessed by 86Rb uptake was independent of gender. Our data provide novel evidence that gender plays a determining role in the physiological properties of centrally administered angiotensin II. PMID:2298467

Doursout, M F; Chelly, J E; Wouters, P; Lawrence, C; Liang, Y Y; Buckley, J P

1990-02-01

65

Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension.  

PubMed

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status, and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus of the hypothalamus, is driven by mitochondrial reactive oxygen species and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the paraventricular nucleus. This was associated with 46% decrease in bone marrow (BM)-derived EPCs and 250% increase in BM ICs, resulting in 5-fold decrease of EPC/IC ratio in the BM. Treatment with mitochondrial-targeted antioxidant, a scavenger of mitochondrial O(2)(-·), intracerebroventricularly but not subcutaneously attenuated angiotensin II-induced hypertension, decreased activation of microglia in the paraventricular nucleus, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with green fluorescent protein-tagged pseudorabies virus. Administration of green fluorescent protein-tagged pseudorabies virus into the BM resulted in predominant labeling of paraventricular nucleus neurons within 3 days, with some fluorescence in the nucleus tractus solitarius, the rostral ventrolateral medulla, and subfornical organ. Taken together, these data demonstrate that inhibition of mitochondrial reactive oxygen species attenuates angiotensin II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in vascular reparative and ICs may perpetuate vascular pathophysiology in this model of hypertension. PMID:23045460

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B; Mocco, J; Raizada, Mohan K

2012-11-01

66

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy  

PubMed Central

Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time RT-PCR. Monophasic action potential duration (MAPD) was recorded in isolated Langendorff-perfused hearts. MAPD restitution was measured, and arrhythmias were induced by burst stimulation. Twenty-two to twenty-six days after treatment, MCT animals had RV hypertension, hypertrophy, and decreased ejection fractions compared with CON. A greater proportion of MCT hearts developed sustained ventricular tachycardias/fibrillation (0.83 MCT vs. 0.14 CON). MAPD was prolonged in RV and less so in the LV of MCT hearts. There were decreased levels of mRNA for K+ channels. Restitution curves of MCT RV were steeper than CON RV or either LV. Dispersion of MAPD was greater in MCT hearts and was dependent on stimulation frequency. Computer simulations based on ion channel gene expression closely predicted experimental changes in MAPD and restitution. We have identified a proarrhythmic substrate in the hearts of MCT-treated rats. We conclude that steeper RV electrical restitution and rate-dependant RV-LV action potential duration dispersion may be contributing mechanisms and be implicated in the generation of arrhythmias associated with in RV hypertension and hypertrophy. PMID:21398591

Benoist, David; Stones, Rachel; Drinkhill, Mark; Bernus, Olivier

2011-01-01

67

Endogenous Angiotensin II Enhances Phenylephrine-Induced Tone in Hypertensive Rats  

Microsoft Academic Search

Subthreshold concentrations of angiotensin II (Ang II) potentiate agonist-induced tone in a variety of blood vessels. We measured in vivo the mesenteric artery diameter and blood flow in 12-week-old normotensive Wistar-Kyoto (WKY) rats (n=20) and spontaneously hypertensive rats (SHR, n=20); systemic blood pressure was monitored contin- uously. Phenylephrine (10 junol\\/L) superfused on the exteri- orized mesentery reduced arterial diameter from

Hong Ying Qiu; Daniel Henrion; Bernard I. Levy

68

Prostatic Relaxation Induced by Loperamide Is Reduced in Spontaneously Hypertensive Rats  

PubMed Central

This paper shows a new finding about the decrease of relaxative response to loperamide in prostate of spontaneously hypertensive rats (SHR) as compare to normal rats (WKY). Authors demonstrated the reduction of ATP-sensitive potassium channels is resposible for this change using immunoblotting analysis and the decrease of action induced by diazoxide. This view is not mentioned before and is the first one reporting this result. PMID:22645476

Lee, Liang-Ming; Lu, Chih-Cheng; Chung, Hsien-Hui; Cheng, Juei-Tang

2012-01-01

69

Hydrogen Sulfide Attenuates Carbon Tetrachloride-Induced Hepatotoxicity, Liver Cirrhosis and Portal Hypertension in Rats  

PubMed Central

Background Hydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension. Methods and Findings Sodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were applied to the rats to investigate the effects of H2S on CCl4-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H2S, hepatic H2S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl4 significantly reduced serum levels of H2S, hepatic H2S production and CSE expression. NaHS attenuated CCl4-induced acute hepatotoxicity by supplementing exogenous H2S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and ?-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters. Conclusions Exogenous H2S attenuates CCl4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H2S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension. PMID:22022478

Tan, Gang; Pan, Shangha; Li, Jie; Dong, Xuesong; Kang, Kai; Zhao, Mingyan; Jiang, Xian; Kanwar, Jagat R.; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

2011-01-01

70

Angiotensin II-Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice  

Microsoft Academic Search

Background—Angiotensin II may contribute to the development and progression of atherosclerotic lesions because of its growth and proinflammatory effects. We sought to determine whether angiotensin II-induced hypertension would augment and accelerate the development of atherosclerotic lesions in apoE-deficient mice. Methods and Results—Angiotensin II (0.7 mg z kg21 z d21 SC) was administered to apoE-deficient mice via osmotic minipumps. The animals

Daiana Weiss; John J. Kools; W. Robert Taylor

2010-01-01

71

Temporary losartan or captopril in young SHR induces malignant hypertension despite initial normotension  

Microsoft Academic Search

Temporary losartan or captopril in young SHR induces malignant hypertension despite initial normotension.BackgroundExposure of normotensive rats to angiotensin-converting enzyme (ACE) inhibitors in early life causes hypertrophy of intrarenal arteries. Similar defects have been found in knockout mice lacking angiotensinogen, ACE, or angiotensin II type 1 (AT1) receptors. On the other hand, transient inhibition of the renin-angiotensin system from 2 weeks

SIMONA RACASAN; BRUNI HAHNEL; Dionne M. van der Giezen; Erwin L. Blezer; ROEL GOLDSCHMEDING; BRANKO BRAAM; WILHEM KRIZ; Hein A. Koomans; Jaap A. Joles

2004-01-01

72

Simvastatin Inhibits Cigarette Smoking-induced Emphysema and Pulmonary Hypertension in Rat Lungs  

Microsoft Academic Search

Rationale: In cigarette smoking-induced chronic obstructive pulmo- nary disease, structural and functional derangements are character- ized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase in- hibitors that have been used as lipid-lowering agents. These drugs also have additional pharmacologic properties, including anti- inflammation, scavenging reactive oxygen species, restoring endo- thelial function, and antithrombogenesis, all of which can counter-

Ji-Hyun Lee; Dong-Soon Lee; Eun-Kyung Kim; Kang-Hyeon Choe; Yeon-Mock Oh; Tae-Sun Shim; Sang-Eun Kim; Yun-Song Lee; Sang-Do Lee

2005-01-01

73

Curcumin protects against cadmium-induced vascular dysfunction, hypertension and tissue cadmium accumulation in mice.  

PubMed

Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)-induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd. PMID:24662163

Kukongviriyapan, Upa; Pannangpetch, Patchareewan; Kukongviriyapan, Veerapol; Donpunha, Wanida; Sompamit, Kwanjit; Surawattanawan, Praphassorn

2014-01-01

74

Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib: preclinical study.  

PubMed

Common adverse effects of angiogenesis inhibition are hypertension and renal injury. To determine the most optimal way to prevent these adverse effects and to explore their interdependency, the following drugs were investigated in unrestrained Wistar Kyoto rats exposed to the angiogenesis inhibitor sunitinib: the dual endothelin receptor antagonist macitentan; the calcium channel blocker amlodipine; the angiotensin-converting enzyme inhibitor captopril; and the phosphodiesterase type 5 inhibitor sildenafil. Mean arterial pressure was monitored telemetrically. After 8 days, rats were euthanized and blood samples and kidneys were collected. In addition, 24-hour urine samples were collected. After sunitinib start, mean arterial pressure increased rapidly by ?30 mm Hg. Coadministration of macitentan or amlodipine largely prevented this rise, whereas captopril or sildenafil did not. Macitentan, captopril, and sildenafil diminished the sunitinib-induced proteinuria and endothelinuria and glomerular intraepithelial protein deposition, whereas amlodipine did not. Changes in proteinuria and endothelinuria were unrelated. We conclude that in our experimental model, dual endothelin receptor antagonism and calcium channel blockade are suitable to prevent angiogenesis inhibition-induced hypertension, whereas dual endothelin receptor antagonism, angiotensin-converting enzyme inhibitor, and phosphodiesterase type 5 inhibition can prevent angiogenesis inhibition-induced proteinuria. Moreover, the variable response of hypertension and renal injury to different antihypertensive agents suggests that these side effects are, at least in part, unrelated. PMID:25185126

Lankhorst, Stephanie; Kappers, Mariëtte H W; van Esch, Joep H M; Smedts, Frank M M; Sleijfer, Stefan; Mathijssen, Ron H J; Baelde, Hans J; Danser, A H Jan; van den Meiracker, Anton H

2014-12-01

75

Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice  

PubMed Central

Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd. PMID:24662163

Kukongviriyapan, Upa; Pannangpetch, Patchareewan; Kukongviriyapan, Veerapol; Donpunha, Wanida; Sompamit, Kwanjit; Surawattanawan, Praphassorn

2014-01-01

76

Essential hypertension seems to result from melatonin-induced epigenetic modifications in area postrema.  

PubMed

Essential hypertension is a complex multifactorial disorder with epigenetic and environmental factors contributing to its prevalence. Epigenetic system is a genetic regulatory mechanism that allows humans to maintain extraordinarily stable patterns of gene expression over many generations. Sympathetic nervous system plays a major role in the maintenance of hypertension and the rostral ventrolateral medulla is the main source of this sympathetic activation. A possible mechanism to explain the sympathetic hyperactivity in the rostral ventrolateral medulla is an action of the area postrema. Area postrema seems to be the region where a shift of the set-point to a higher operating pressure occurs resulting in hypertension. But, how can a shift occur in the area postrema. We propose that melatonin-induced epigenetic modifications in the neurons of area postrema plays a role in this shift. Area postrema is reported to contain high levels of melatonin receptors that play a role in the epigenetic modifications in certain cells. Environmental stressors cause epigenetic modifications in the neurons of area postrema via the pineal hormone melatonin and these changes lead to a shift in the set-point to a higher operating pressure. This signal is then sent via efferent projections to key medullary sympathetic nuclei in rostral ventrolateral medulla resulting in increases in sympathetic nerve activity. This model may explain the long-term alterations in sympathetic activity in essential hypertension. PMID:16434146

Irmak, M K; Sizlan, A

2006-01-01

77

Intrarenal ghrelin receptor antagonism prevents high-fat diet-induced hypertension in male rats.  

PubMed

Excess weight gain contributes up to 65% of the risk of primary hypertension, and the increase in blood pressure in response to high-fat diet (HFD) is preceded by significant increases in renal tubular sodium (Na(+)) reabsorption. In normal rats, intrarenal ghrelin infusion increases distal nephron-dependent Na(+) reabsorption via activation of the intrarenal ghrelin receptor (GHSR). This study focusses on the role of intrarenal GHSR-mediated Na(+) reabsorption in HFD-induced hypertension. Dahl salt-sensitive rats received standard diet or HFD for 6 weeks. Rats underwent uninephrectomy and osmotic minipump implantation for chronic intrarenal delivery of vehicle (0.25 ?L/h × 28 d), selective GHSR antagonist [D-Lys-3]-growth hormone releasing peptide-6 (0.2?M/d), or GHSR inverse agonist [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P (SUB-P) (3.6?M/d). HFD rats with vehicle pumps had significantly increased renal GHSR expression compared with standard diet (0.092 ± 0.005 vs 0.065 ± 0.004 arbitrary units; P < .05), whereas acyl ghrelin levels were similar (16.3±6.2 vs 15.7±8.7 pg/g tissue). HFD rats with vehicle pumps became hypertensive after 2 weeks (P < .05) and showed a significant reduction in 24-hour urine Na(+) before hypertension. At this time, these rats showed an increase in collecting duct ?-epithelial Na(+) channel, thereby providing a potential mechanism for the excess Na(+) reabsorption. In contrast, HFD rats with [D-Lys-3]-growth hormone releasing peptide-6 or SUB-P pumps never became hypertensive and did not show the reduction in urine Na(+). Because SUB-P blocks the constitutive, but not ghrelin-dependent, activity of the GHSR, and HFD-induced ?-epithelial Na(+) channel up-regulation was abolished during GHSR antagonism, these data suggest that HFD increases the constitutive activity of renal GHSR to increase Na(+) reabsorption and induce hypertension in rats. PMID:24797629

Kemp, Brandon A; Howell, Nancy L; Gildea, John J; Padia, Shetal H

2014-07-01

78

Carbonyl stress induces hypertension and cardio-renal vascular injury in Dahl salt-sensitive rats.  

PubMed

One major precursor of carbonyl stress, methylglyoxal (MG), is elevated in the plasma of chronic kidney disease (CKD) patients, and this precursor contributes to the progression of vascular injury, hypertension and renal injury in diabetic nephropathy patients. This molecule induces salt-sensitive hypertension via a reactive oxygen species-mediated pathway. We examined the role of MG in the pathogenesis of hypertension and cardio-renal injury in Dahl salt-sensitive (Dahl S) rats, which is a rat model of CKD. Nine-week-old Dahl S rats were fed a 1% NaCl diet, and 1% MG was added to their drinking water for up to 12 weeks. Blood pressure and cardio-renal injuries were compared with rats treated with tap water alone. The angiotensin II receptor blocker (ARB), candesartan (10?mg?kg(-1)?day(-1)), was administered to MG Dahl S rats to determine the impact of this drug on the pathogenesis of MG-induced CKD. A progressive increase in systolic blood pressure was observed (123±1-148±5?mm?Hg) after 12 weeks of MG administration. MG administration significantly increased urinary albumin excretion, glomerular sclerosis, tubular injury, myocardial collagen content and cardiac perivascular fibrosis. MG also enhanced the renal expression of N?-carboxyethyl-lysine (an advanced glycation end product), 8-hydroxydeoxyguanosine (a marker of oxidative stress), macrophage (ED-1) positive cells (a marker of inflammation) and nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity. Candesartan treatment for 4 weeks significantly reduced these parameters. These results suggest that MG-induced hypertension and cardio-renal injury and increased inflammation and carbonyl and oxidative stress, which were partially preventable by an ARB. PMID:23364337

Chen, Xianguang; Mori, Takefumi; Guo, Qi; Hu, Chunyan; Ohsaki, Yusuke; Yoneki, Yoshimi; Zhu, Wanjun; Jiang, Yue; Endo, Satoshi; Nakayama, Keisuke; Ogawa, Susumu; Nakayama, Masaaki; Miyata, Toshio; Ito, Sadayoshi

2013-04-01

79

Soman-induced hypertension in conscious rats is mediated by prolonged central muscarinic stimulation.  

PubMed

The acetylcholinesterase inhibitor, soman, induces marked and sustained hypertension and tachycardia associated with a convulsive syndrome in rats. The aims of the present study were to distinguish between the cardiovascular and convulsant effects of soman and to determine whether the maintenance of the soman-induced hypertension and tachycardia depends solely on a central muscarinic effect. To this end, using a computerised analysis of blood pressure (BP) in conscious freely moving rats, we examined the consequences on the increase in mean BP (MBP) and heart rate (HR) induced by soman (60 micrograms/kg, i.v.) of 1) a pre-treatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.) and 2) atropine sulphate (10 mg/kg, i.v.) administered 10 or 60 min after the intoxication. Pretreatment with diazepam prevented the convulsions, assessed by electroencephalogram (EEG) recording, but modified neither the magnitude nor the kinetics of the pressor and tachycardic effects of soman (delta MBP = 74 +/- 2 and 73 +/- 5 mmHg, delta HR = 69 +/- 10 and 79 +/- 7 bpm, maximum MBP = 186 +/- 3 and 182 +/- 6 mmHg, maximum HR = 545 +/- 9 and 522 +/- 16 bpm in solvent- (n = 8) and diazepam- (n = 8) pre-treated rats, respectively). Whatever its time of administration, atropine sulphate fully and immediately reversed the rise in BP induced by soman. The soman-induced tachycardia was also suppressed by atropine administered 10 min after soman whereas it persisted when atropine was injected 60 min after the intoxication. These results show that the cardiovascular effects of soman can occur independently of the convulsive syndrome and that the maintenance of the soman-induced hypertension depends entirely on a permanent central muscarinic stimulation. PMID:10456288

Létienne, R; Julien, C; Barrès, C; Lallement, G; Baubichon, D; Bataillard, A

1999-01-01

80

Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation  

PubMed Central

Background In addition to systemic inflammation, neuroinflammation in the brain, which enhances sympathetic drive, plays a significant role in cardiovascular diseases, including hypertension. Oxidative stress in rostral ventrolateral medulla (RVLM) that augments sympathetic outflow to blood vessels is involved in neural mechanism of hypertension. We investigated whether neuroinflammation and oxidative stress in RVLM contribute to hypertension following chronic systemic inflammation. Methods In normotensive Sprague-Dawley rats, systemic inflammation was induced by infusion of Escherichia coli lipopolysaccharide (LPS) into the peritoneal cavity via an osmotic minipump. Systemic arterial pressure and heart rate were measured under conscious conditions by the non-invasive tail-cuff method. The level of the inflammatory markers in plasma or RVLM was analyzed by ELISA. Protein expression was evaluated by Western blot or immunohistochemistry. Tissue level of superoxide anion (O2·-) in RVLM was determined using the oxidation-sensitive fluorescent probe dihydroethidium. Pharmacological agents were delivered either via infusion into the cisterna magna with an osmotic minipump or microinjection bilaterally into RVLM. Results Intraperitoneal infusion of LPS (1.2?mg/kg/day) for 14?days promoted sustained hypertension and induced a significant increase in plasma level of C-reactive protein, tumor necrosis factor-? (TNF-?), or interleukin-1? (IL-1?). This LPS-induced systemic inflammation was accompanied by activation of microglia, augmentation of IL-1?, IL-6, or TNF-? protein expression, and O2·- production in RVLM, all of which were blunted by intracisternal infusion of a cycloxygenase-2 (COX-2) inhibitor, NS398; an inhibitor of microglial activation, minocycline; or a cytokine synthesis inhibitor, pentoxifylline. Neuroinflammation in RVLM was also associated with a COX-2-dependent downregulation of endothelial nitric oxide synthase and an upregulation of intercellular adhesion molecule-1. Finally, the LPS-promoted long-term pressor response and the reduction in expression of voltage-gated potassium channel, Kv4.3 in RVLM were antagonized by minocycline, NS398, pentoxifylline, or a superoxide dismutase mimetic, tempol, either infused into cisterna magna or microinjected bilaterally into RVLM. The same treatments, on the other hand, were ineffective against LPS-induced systemic inflammation. Conclusion These results suggest that systemic inflammation activates microglia in RVLM to induce COX-2-dependent neuroinflammation that leads to an increase in O2·- production. The resultant oxidative stress in RVLM in turn mediates neurogenic hypertension. PMID:22958438

2012-01-01

81

Lack of Bcr and Abr Promotes Hypoxia-Induced Pulmonary Hypertension in Mice  

PubMed Central

Background Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined. Methodology/Principal Findings Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr?/? and abr?/? macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia. Conclusions Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells. PMID:23152932

Lim, Min; Arutyunyan, Anna; Groffen, John; Heisterkamp, Nora

2012-01-01

82

Cardiovascular Responses Induced by Obstructive Apnea Are Enhanced in Hypertensive Rats Due to Enhanced Chemoreceptor Responsivity  

PubMed Central

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n?=?14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea. PMID:24466272

Angheben, Juliana M. M.; Schoorlemmer, Guus H. M.; Rossi, Marcio V.; Silva, Thiago A.; Cravo, Sergio L.

2014-01-01

83

Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity.  

PubMed

Spontaneously hypertensive rats (SHR), like patients with sleep apnea, have hypertension, increased sympathetic activity, and increased chemoreceptor drive. We investigated the role of carotid chemoreceptors in cardiovascular responses induced by obstructive apnea in awake SHR. A tracheal balloon and vascular cannulas were implanted, and a week later, apneas of 15 s each were induced. The effects of apnea were more pronounced in SHR than in control rats (Wistar Kyoto; WKY). Blood pressure increased by 57±3 mmHg during apnea in SHR and by 28±3 mmHg in WKY (p<0.05, n?=?14/13). The respiratory effort increased by 53±6 mmHg in SHR and by 34±5 mmHg in WKY. The heart rate fell by 209±19 bpm in SHR and by 155±16 bpm in WKY. The carotid chemoreceptors were then inactivated by the ligation of the carotid body artery, and apneas were induced two days later. The inactivation of chemoreceptors reduced the responses to apnea and abolished the difference between SHR and controls. The apnea-induced hypertension was 11±4 mmHg in SHR and 8±4 mmHg in WKY. The respiratory effort was 15±2 mmHg in SHR and 15±2 mmHg in WKY. The heart rate fell 63±18 bpm in SHR and 52±14 bpm in WKY. Similarly, when the chemoreceptors were unloaded by the administration of 100% oxygen, the responses to apnea were reduced. In conclusion, arterial chemoreceptors contribute to the responses induced by apnea in both strains, but they are more important in SHR and account for the exaggerated responses of this strain to apnea. PMID:24466272

Angheben, Juliana M M; Schoorlemmer, Guus H M; Rossi, Marcio V; Silva, Thiago A; Cravo, Sergio L

2014-01-01

84

Inhibition of cadmium-induced hypertension in rats.  

PubMed

In a low cadmium environment, adding 10 parts per million (ppm) of cadmium to the drinking water of rats for 3 to 18 months induced increases in systolic pressure averaging 12 to 18 mm Hg. The pressor effect of the cadmium was inhibited by adding 3.6 ppm of selenium or 200 ppm of zinc to the drinking water or by dissolving the cadmium in hard water rather than deionized water. A second experiment with 2.5 ppm of cadmium and smaller amounts of selenium and zinc was confirmatory. Exposure to 10 ppm of cadmium increased renal, hepatic, and cardiac cadmium many fold from barely detectable control levels; however, the increases were much less when the cadmium was dissolved in hard water. Cadmium exposure also increased tissue zinc by 30 to 60%. The addition of selenium to cadmium further increased cardiac cadmium, but the addition of zinc to cadmium had no further effect on tissue cadmium. Tissue selenium concentrations were suggestively but not significantly higher following selenium exposure. Cadmium alone, or combined with selenium or zinc, increased renal copper; while the combination of cadmium and selenium increased hepatic copper. PMID:7367855

Perry, H M; Erlanger, M W; Blotcky, A J; Perry, E F

1980-03-01

85

Impairment of the low-affinity state ?1-adrenoceptor-induced relaxation in spontaneously hypertensive rats  

PubMed Central

In hypertension, a decrease of the vascular ?-adrenergic relaxation has been described. However, the specific involvement of each ?-adrenoceptor (?-AR) subtype, in particular the low-affinity state of ?1-AR, has not yet been evaluated. We investigated whether the low-affinity state of ?1-AR-induced relaxation was impaired in Spontaneously Hypertensive Rats (SHR). The relaxant responses to CGP 12177 and cyanopindolol, low-affinity state ?1-AR agonists (with ?1-/?2-AR antagonistic and partial ?3-AR agonistic properties) were evaluated on thoracic aortic rings isolated from 12-weeks-old Wistar Kyoto rats (WKY) and SHR. In WKY, CGP 12177 and cyanopindolol produced an endothelium and nitric oxide (NO)-independent relaxation. CGP 12177-induced endothelium-independent relaxation was not modified either by ?1-, ?2-AR (nadolol) or ?3-AR (L-748337 or SR 59230A) antagonists but was significantly reduced by high concentrations of CGP 20712A (P<0.05). This relaxation was also reduced by adenylyl cyclase inhibitors, SQ 22536 or MDL 12330A. In SHR, CGP 12177 produced mainly an endothelium and NO-dependent relaxation. This effect was not modified by nadolol, but was strongly reduced by ?3-AR blockade. Endothelium-independent relaxation to CGP 12177 was not altered by adenylyl cyclase inhibition, but was amplified in preparations from pertussis toxin-pretreated SHR. The immunohistochemical analysis revealed an upregulation of ?3-AR in the endothelial layer of SHR aorta, whereas the ?3-AR-induced relaxation was not modified. In conclusion, we demonstrated an impaired low-affinity state of the ?1-AR-induced relaxation and an upregulation of the ?3-AR in hypertension. Some clinical implications of those findings are discussed. PMID:15466443

Mallem, Mohamed Yassine; Toumaniantz, Gilles; Serpillon, Sabrina; Gautier, Freddy; Gogny, Marc; Desfontis, Jean-Claude; Gauthier, Chantal

2004-01-01

86

Clopidogrel preserves whole kidney autoregulatory behavior in ANG II-induced hypertension.  

PubMed

This study tested the hypothesis that P2Y12 receptor blockade with clopidogrel preserves renal autoregulatory ability during ANG II-induced hypertension. Clopidogrel was administered orally to male Sprague-Dawley rats chronically infused with ANG II. After 14 days of treatment, whole kidney autoregulation of renal blood flow was assessed in vivo in pentobarbital-anesthetized rats using an ultrasonic flow probe placed around the left renal artery. In ANG II-vehicle-treated rats, decreasing arterial pressure over a range from 160 to 100 mmHg resulted in a 25 ± 5% decrease in renal blood flow, demonstrating a significant loss of autoregulation with an autoregulatory index of 0.66 ± 0.15. However, clopidogrel treatment preserved autoregulatory behavior in ANG II-treated rats to levels indistinguishable from normotensive sham-operated (sham) rats (autoregulatory index: 0.04 ± 0.14). Compared with normotensive sham-vehicle-treated rats, ANG II infusion increased renal CD3-positive T cell infiltration by 66 ± 6%, induced significant thickening of the preglomerular vessels and glomerular basement membrane and increased glomerular collagen I deposition, tubulointerstitial fibrosis, damage to the proximal tubular brush border, and protein excretion. Clopidogrel significantly reduced renal infiltration of T cells by 39 ± 9% and prevented interstitial artery thickening, ANG II-induced damage to the glomerular basement membrane, deposition of collagen type I, and tubulointerstitial fibrosis, despite the maintenance of hypertension. These data demonstrate that systemic P2Y12 receptor blockade with clopidogrel protects against impairment of autoregulatory behavior and renal vascular injury in ANG II-induced hypertension, possibly by reducing renal T cell infiltration. PMID:24477682

Osmond, David A; Zhang, Shali; Pollock, Jennifer S; Yamamoto, Tatsuo; De Miguel, Carmen; Inscho, Edward W

2014-03-15

87

Increased cardiac output contributes to the development of chronic intermittent hypoxia-induced hypertension.  

PubMed

Chronic intermittent hypoxia (CIH) in animal models has been shown to result in hypertension and elevation of sympathetic nervous system activity. Sympathetically mediated vasoconstriction is believed to be the primary mechanism underpinning CIH-induced hypertension; however, the potential contribution of the heart is largely overlooked. We sought to determine the contribution of cardiac output (CO) and lumbar sympathetic control of the hindlimb circulation to CIH-induced hypertension. Male Wistar rats (n = 64) were exposed to 2 weeks of CIH [cycles of 90 s hypoxia (5% O2 nadir) and 210 s normoxia] or normoxia for 8 h day(-1). Under urethane anaesthesia, CIH-treated animals developed hypertension (81.4 ± 2.2 versus 91.6 ± 2.4 mmHg; P < 0.001), tachycardia (397 ± 8 versus 445 ± 7 beats min(-1); P < 0.001) and an increased haematocrit (42.4 ± 0.4 versus 45.0 ± 0.4%; P < 0.001). Echocardiography revealed that CIH exposure increased the CO [19.3 ± 1.7 versus 25.8 ± 2.6 ml min(-1) (100 g)(-1); P = 0.027] with no change in total peripheral resistance (4.93 ± 0.49 versus 4.17 ± 0.34 mmHg ml(-1) min(-1); P = 0.123). Sympathetic ganglionic blockade revealed that sympathetic control over blood pressure was not different (-27.7 ± 1.6 versus -32.3 ± 2.9 mmHg; P = 0.095), and no chronic vasoconstriction was found in the hindlimb circulation of CIH-treated animals (39.4 ± 2.5 versus 38.0 ± 2.4 ?l min(-1) mmHg(-1); P = 0.336). Lumbar sympathetic control over the hindlimb circulation was unchanged in CIH-treated animals (P = 0.761), although hindlimb arterial sympathetic density was increased (P = 0.012) and vascular sensitivity to phenylephrine was blunted (P = 0.049). We conclude that increased CO is sufficient to explain the development of CIH-induced hypertension, which may be an early adaptive response to raise O2 flow. We propose that sustained elevated cardiac work may ultimately lead to heart failure. PMID:25063839

Lucking, Eric F; O'Halloran, Ken D; Jones, James F X

2014-10-01

88

Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar–Kyoto rats  

Microsoft Academic Search

Rationale  Chronic intermittent hypoxia (CIH) is thought to induce several cardiovascular effects in patients with obstructive sleep\\u000a apnoea (OSA). However, the effects of CIH on patients with long-standing hypertension are unknown.\\u000a \\u000a \\u000a \\u000a \\u000a Purpose  This prospective study aimed to investigate the influence of combined OSA and hypertension on cardiomyocyte death.\\u000a \\u000a \\u000a \\u000a Methods  Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to repetitive hypoxia–reoxygenation cycles

Tsung-I Chen; Ching-Jung Lai; Chien-Ju Hsieh; Ke-Li Tsai; Kun-Ta Yang

89

Role of the a2B-Adrenergic Receptor in the Development of Salt-Induced Hypertension  

Microsoft Academic Search

Salt sensitivity is a common trait in patients with essential hypertension and seems to have both an inherited and an acquired component (eg, is influenced by aging and renal insufficiency). Experimental evidence suggests that salt loading induces hypertension via a neurogenic mechanism mediated by the a2-adrenergic receptors (a2-AR). To explore the a2-AR subtype involved in this mechanism, we studied 2

Konstantinos P. Makaritsis; Diane E. Handy; Conrado Johns; Brian Kobilka; Irene Gavras; Haralambos Gavras

90

Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet  

PubMed Central

We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT1 receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR).SHR (8–9 weeks old) on high-sodium diet were given CsA (5?mg?kg?1d??1 s.c.) for 6 weeks. The rats were treated concomitantly either with enalapril (30?mg?kg?1d??1 p.o.) or valsartan (3 or 30?mg?kg?1 d??1 p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B2 receptor antagonist icatibant (HOE 140, 500??g?kg?1 d??1 s.c.) during the last 2 weeks of enalapril treatment.Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion.CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis.Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology.The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR. PMID:10903974

Lassila, Markus; Finckenberg, Piet; Pere, Anna-Kaisa; Krogerus, Leena; Ahonen, Juhani; Vapaatalo, Heikki; Nurminen, Marja-Leena

2000-01-01

91

Manganese Porphyrin Reduces Retinal Injury Induced by Ocular Hypertension in Rats  

PubMed Central

This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP5+) treatment in a rat model of elevated intraocular pressure (EIOP). Rats were randomly divided into different experimental groups which received either intraperitoneal MnTnHex-2-PyP5+ (0.1 mg/kg/day), intragastric NOS inhibitor (S-methylthiourea: SMT; 5 mg/kg/day) or both agents for a period of 6 weeks. Ocular hypertension was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. Neuroprotective effects of given treatments were determined via electrophysiological measurements of visual evoked potentials (VEP) while retina and vitreous levels of MnTnHex-2-PyP5+ were measured via LC-MS/MS. Latencies of all VEP components (P1, N1, P2, N2, P3) were significantly prolonged (p<0.05) in EIOP and returned to control levels following all three treatment protocols. Ocular hypertension significantly increased retinal protein nitration (p<0.001) which returned to baseline levels in all treated groups. NOS-2 expression and nitrate/nitrite levels were significantly greater in non-treated rats with EIOP. Retinal TUNEL staining showed apoptosis in all ocular hypertensive rats. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of MnTnHex-2-PyP5+ treatment and NOS inhibition in ocular hypertension. PMID:21669199

Dogan, Serdar; Unal, Mustafa; Ozturk, Nihal; Yargicoglu, Piraye; Cort, Aysegul; Spasojevic, Ivan; Batinic-Haberle, Ines; Aslan, Mutay

2011-01-01

92

Protective Effects of Methylsulfonylmethane on Hemodynamics and Oxidative Stress in Monocrotaline-Induced Pulmonary Hypertensive Rats  

PubMed Central

Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400?mg/kg/day doses 10 days before a single dose of 60?mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense. PMID:23118745

Mohammadi, Sadollah; Najafi, Moslem; Hamzeiy, Hossein; Maleki-Dizaji, Nasrin; Pezeshkian, Masoud; Sadeghi-Bazargani, Homayon; Darabi, Masoud; Mostafalou, Sara; Bohlooli, Shahab; Garjani, Alireza

2012-01-01

93

Hydrogen Sulfide Attenuates Carbon Tetrachloride-Induced Hepatotoxicity, Liver Cirrhosis and Portal Hypertension in Rats  

Microsoft Academic Search

BackgroundHydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension.Methods and FindingsSodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were

Gang Tan; Shangha Pan; Jie Li; Xuesong Dong; Kai Kang; Mingyan Zhao; Xian Jiang; Jagat R. Kanwar; Haiquan Qiao; Hongchi Jiang; Xueying Sun; Antonio Bertoletti

2011-01-01

94

20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension  

PubMed Central

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5?-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14?/? mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 ?m) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12–20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 ?m; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID:23825080

Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L.; Falck, John R.; Capdevila, Jorge H.

2013-01-01

95

Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension.  

PubMed

Arterial hypertension is a major risk factor that can lead to complication of peripheral vascular disease due, in part, to endothelial dysfunction. Because sodium nitrite (SN) can be converted to nitric oxide (NO), which counteracts endothelial dysfunction, we explored the effect of nitrite on neovascularization following hind limb ischemia in different models of hypertension (HT). Chronic delivery of angiotensin II (Ang II, 400 ng/kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1 g/L) was used for a 2-week period to induce hypertension. Mice were subjected to femoral artery ligation-induced ischemia in the hind limb followed by treatment with SN (50 mg/L) for 2 weeks. SN significantly reduced systolic arterial blood pressure in mice receiving Ang II and L-NAME but had no effect in sham animals. After 2 weeks, blood flow and microangiography showed 60 %?±?1.0 recovery in sham compared with 40 %?±?1.3 in HT mice. Importantly, sham and HT mice treated with SN showed a 100 % blood flow recovery associated with normalization in capillary density. The inhibition of xanthine-oxido-reductase (allopurinol) or VEGFR (SU-5416) prevented the neovascularization in HT mice treated with SN. Cyclic GMP (cGMP) content in the hind limb was significantly increased in mice treated with SN compared with non-treated mice. Nitrite/nitrate content was only increased in the sham group treated with SN. Immunoprecipitation and Western blot analysis revealed an increase in eNOS/Akt/VEGFR phosphorylation in skeletal muscle from mice treated with SN compared with non-treated mice. Our findings indicate that SN therapy rescues the neovascularization and blood flow recovery in the ischemic hind limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways. PMID:23053479

Amin, Ali; Choi, Soo-Kyoung; Osman-Elazeik, Yehia; Badr El-Din, Nariman K; Kevil, Christopher G; Navar, Louis G; Kadowitz, Philip; Trebak, Mohamed; Matrougui, Khalid

2012-12-01

96

Endothelin-1 is not a Mechanism of IL-17 Induced Hypertension during Pregnancy  

PubMed Central

Preeclampsia is characterized as new onset maternal hypertension and proteinuria after 20 weeks gestation. Studies suggest that endothelin (ET-1) is a regulator of vascular function in preeclampsia and plays a major role in mediating chronic reduction in uterine perfusion pressure (RUPP)-induced hypertension. We recently demonstrated a role for the autoimmune cytokine interleukin 17 (IL-17) in causing placental oxidative stress and hypertension during pregnancy. In this current study, we investigated the role of ET-1 as a potential mechanism by which TH17 cells and IL-17 mediate hypertension in preeclampsia. While IL-17 infusion into normal pregnant rats increased blood pressure in a dose-responsive manner (98+/-2 mmHg in NP (n=20) to 105+/-3 mmHg in IL-17 (50pg/day, n=20) to 120+/-4 mmHg in IL-17 (100pg/day, n=10) to 123+/-3 mmHg in IL-17 (150 pg/day, n=7), it decreased local endothelin in placentas (NP (n=10) 7.5±0.3; IL-17 (100 pg/day, n=5) 6.4±0.2; IL-17 (150 pg/day, n=12) 4.5+1.5) and renal cortices (NP (n=8) 7.9 + 0.4; IL-17 (100 pg/day, n=6) 7.1±0.4; IL-17 (150 pg/day, n=4) 1.6 +0.7 during pregnancy. In addition, increasing IL-17 directly reduced secretion of ET-1 by human umbilical venous endothelial cells (HUVECs). HUVEC ET-1 secretion decreased from that seen in serum free media 42.7±7.7 pg/ml to 36.2 ± 5.9 pg/ml at 10 pg IL-17 to 31.3 ± 5.1 pg/ml at 10 ?g IL-17. Our observations suggest that IL-17 negatively regulates the ET-1 pathway in local tissues and cultured endothelial cells and that the ET-1 pathway is not a mechanism by which IL-17 causes hypertension during pregnancy.

Cornelius, Denise C; Wallace, Kedra; Kiprono, Luissa; Dhillon, Pushpinder; Moseley, Janae; LaMarca, Babbette

2014-01-01

97

Caffeine intake improves fructose-induced hypertension and insulin resistance by enhancing central insulin signaling.  

PubMed

Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1(S307)) and reversed Akt(S473) and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production of superoxide and expression of receptor of advanced glycation end product in the NTS. These results suggest that caffeine may enhance insulin receptor substrate 1-phosphatidylinositol 3-kinase-Akt-neuronal nitric oxide synthase signaling to decrease blood pressure by abolishing superoxide production in the NTS. PMID:24366086

Yeh, Tung-Chen; Liu, Chun-Peng; Cheng, Wen-Han; Chen, Bo-Rong; Lu, Pei-Jung; Cheng, Pei-Wen; Ho, Wen-Yu; Sun, Gwo-Ching; Liou, Jau-Cheng; Tseng, Ching-Jiunn

2014-03-01

98

Complement C3 Deficiency Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in Mice  

PubMed Central

Background Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension. Methodology/Principal Findings Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3?/? hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3?/? mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3?/? mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3?/? mice. Conclusions Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans. PMID:22194859

Bauer, Eileen M.; Zheng, Han; Comhair, Suzy; Erzurum, Serpil; Billiar, Timothy R.; Bauer, Philip M.

2011-01-01

99

Vascular smooth muscle, endothelial regulation and effects of aspirin in hypertension.  

PubMed

Dysfunction of vascular smooth muscle (VSM) is at the center of occlusive disorders of the cardiovascular system such as hypertension, atherosclerosis, coronary artery disease and hypoxia. In addition to circulating biogenic amines and various neurotransmitters originating from the central nervous system and endocrine system, various autocoids of arachidonic acid metabolism in the blood as well as in the endothelium play an important regulatory role in the maintenance of the tone and the contractile function of VSM. A monolayer of endothelial cells lining the heart and large blood vessels is responsible for producing and releasing both endocrine and paracrine substances such as endothelins, nitric oxide, prostaglandins and prostacyclins. Aspirin, (acetylsalicylic acid/ASA) an ancient remedy against fever and pain, is emerging as an effective drug not only against occlusive disorders but also against various cancers and the AIDs virus. During pregnancy induced hypertension (PIH) and in occlusive disorders, aspirin provides relief through inhibition of cyclooxygenase, an enzyme required for the metabolism of arachidonic acid to produce prostaglandins and prostacyclins in platelets and in endothelial cells. Because of its unique molecular constitution, synergistic ability and solubility in the lipidic environment, various mechanisms of aspirin's actions are being currently investigated. In this review, the effect of aspirin on the regulation of VSM in the presence and absence of endothelium are discussed. PMID:9556499

Rahmani, M A

1998-04-27

100

Selective endothelin-A receptor blockade attenuates endotoxin-induced pulmonary hypertension and pulmonary vascular dysfunction  

PubMed Central

Abstract Endothelin-1 is a potent mediator of sepsis-induced pulmonary hypertension (PH). The pulmonary vascular effects of selective blockade of endothelin receptor subtype A (ETAR) during endotoxemia remain unknown. We hypothesized that selective ETAR antagonism attenuates endotoxin-induced PH and improves pulmonary artery (PA) vasoreactivity. Adult male Sprague-Dawley rats (250–450 g) received lipopolysaccharide (LPS; Salmonella typhimurium; 20 mg/kg intraperitoneally) or vehicle 6 hours before hemodynamic assessment and tissue harvest. The selective ETAR antagonist sitaxsentan (10 or 20 mg/kg) or vehicle was injected intravenously 3 hours after receipt of LPS. Right ventricular systolic pressure, mean arterial pressure (MAP), cardiac output (CO), oxygenation (P/F ratio), and serum bicarbonate were measured. Bronchoalveolar lavage (BAL) cell differential and lung wet-to-dry ratios were obtained. Endothelium-dependent and endothelium-independent vasorelaxations were determined in isolated PA rings. PA interleukin (IL)-1?, IL-6, tumor necrosis factor ? (TNF-?), and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) were measured. LPS caused PH, decreased MAP, CO, and serum bicarbonate, and increased PA IL-1?, IL-6, TNF-?, and iNOS mRNA. Sitaxsentan attenuated sepsis-induced PH and increased MAP. The P/F ratio, CO, serum bicarbonate, and BAL neutrophilia were not affected by sitaxsentan. In isolated PA rings, while not affecting phenylephrine-induced vasocontraction or endothelium-dependent relaxation, sitaxsentan dose-dependently attenuated LPS-induced alterations in endothelium-independent relaxation. PA cytokine mRNA levels were not significantly attenuated by ETAR blockade. We conclude that ETAR blockade attenuates endotoxin-induced alterations in systemic and PA pressures without negatively affecting oxygenation. This protective effect appears to be mediated not by attenuation of sepsis-induced cardiac dysfunction, acidosis, or alveolar inflammation but rather by improved endothelium-independent vasorelaxation. PMID:25006449

2014-01-01

101

Alterations in structure and mechanics of resistance arteries from ouabain-induced hypertensive rats.  

PubMed

We have previously described that chronic administration of ouabain induces hypertension and functional alterations in mesenteric resistance arteries. The aim of this study was to analyze whether ouabain treatment also alters the structural and mechanical properties of mesenteric resistance arteries. Wistar rats were treated for 5 wk with ouabain (8.0 microg/day sc). The vascular structure and mechanics of the third-order branches of the mesenteric artery were assessed with pressure myography and confocal microscopy. Total collagen content was determined by picrosirius red staining, collagen I/III was analyzed by Western blot, and elastin was studied by confocal microscopy. Vascular reactivity was analyzed by wire myography. Internal and external diameters and cross-sectional area were diminished, whereas the wall-to-lumen ratio was increased in arteries from ouabain-treated rats compared with controls. In addition, arteries from ouabain-treated rats were stiffer. Ouabain treatment decreased smooth muscle cell number and increased total and I/III collagens in the vascular wall. However, this treatment did not modify adventitia and media thickness, nuclei morphology, elastin structure, and vascular reactivity to norepinephrine and acetylcholine. The present work shows hypotrophic inward remodeling of mesenteric resistance arteries from ouabain-treated rats that seems to be the consequence of a combination of decreased cell number and impaired distension of the artery, possibly due to a higher stiffness associated with collagen deposition. The narrowing of resistance arteries could play a role in the pathogenesis of hypertension in this model. PMID:16473962

Briones, Ana M; Xavier, Fabiano E; Arribas, Silvia M; González, M Carmen; Rossoni, Luciana V; Alonso, María J; Salaices, Mercedes

2006-07-01

102

Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats  

PubMed Central

Background CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood. Methods In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats. Results We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats. Conclusions The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment. PMID:21294880

2011-01-01

103

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats  

NASA Technical Reports Server (NTRS)

We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

1998-01-01

104

PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy.  

PubMed

Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

2014-01-01

105

PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy  

PubMed Central

Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

2014-01-01

106

The new NO donor Terpy induces similar relaxation in mesenteric resistance arteries of renal hypertensive and normotensive rats.  

PubMed

The present work aimed to investigate the cellular mechanisms involved on the vasorelaxation induced by the new nitric oxide donor [Ru(terpy)(bdq)NO](3+) (Terpy) in isolated mesenteric resistance artery and to compare the vascular responses in isolated vessels from 2K and 2K-1C hypertensive rats. We have used this artery because it is important to the control of vascular resistance and consequently to the blood pressure control. The NO donor Terpy induced relaxation in a concentration-dependent way in mesenteric resistance arteries. There were no differences between renal hypertensive (2K-1C) and normotensive (2K) in Terpy-induced relaxation neither in NO released. The relaxation induced by Terpy was inhibited by the soluble guanylyl-cyclase (sGC) inhibitor ODQ both in 2K and in 2K-1C with similar amplitude. In agreement with these data, the protein expression of the subunits ?1 and ?1 of the enzyme sGC was not different between 2K-1C and 2K mesenteric bed. The relaxation induced by Terpy was inhibited by the cGMP-dependent protein kinase (G kinase) inhibitor or by the non-selective K(+) channel blocker tetraethylamonium (TEA), but with no difference between 2K-1C and 2K arteries. The relaxation induced by Terpy was also inhibited by the SERCA inhibitor thapsigargin in both groups. Taken together, these results show that the vascular relaxation induced by the NO donor [Ru(terpy)(bdq)NO](3+) involves the activation of NO/sGC/cGMP/GK pathway, activation of K(+) channels sensitive to TEA and SERCA in normotensive and renal hypertensive rat mesenteric resistance arteries. Surprisingly, Terpy-induced vasorelaxation is similar in mesenteric resistance arteries of renal hypertensive and normotensive rats. PMID:23968803

Araújo, Alice V; Pereira, Amanda C; Grando, Marcella D; da Silva, Roberto S; Bendhack, Lusiane M

2013-11-30

107

Thymosin Beta 4 Protects Mice from Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy  

PubMed Central

Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (T?4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether T?4 has any protective role in PH. The purpose of this study is to evaluate the whether T?4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with T?4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that T?4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for T?4 and may consider as vasculo-protective agent for the treatment of PH induced RVH. PMID:25412097

Wu, Liling; Gupta, Sudhiranjan

2014-01-01

108

Structural and functional prevention of hypoxia-induced pulmonary hypertension by individualized exercise training in mice.  

PubMed

Pulmonary hypertension (PH) is a disease with a poor prognosis characterized by a vascular remodeling process and an increase in pulmonary vascular resistance. While a variety of reports demonstrated that exercise training exerts beneficial effects on exercise performance and quality of life in PH patients, it is not known how physical exercise affects vascular remodeling processes occurring in hypoxia-induced PH. Therefore, we investigated the effect of individualized exercise training on the development of hypoxia-induced PH in mice. Training effects were compared with pharmacological treatment with the phosphodiesterase 5 inhibitor Sildenafil or a combination of training plus Sildenafil. Trained mice who received Sildenafil showed a significantly improved walking distance (from 88.9 ± 8.1 to 146.4 ± 13.1 m) and maximum oxygen consumption (from 93.3 ± 2.9 to 105.5 ± 2.2% in combination with Sildenafil, to 102.2 ± 3.0% with placebo) compared with sedentary controls. Right ventricular systolic pressure, measured by telemetry, was at the level of healthy normoxic animals, whereas right heart hypertrophy did not benefit from training. Most interestingly, the increase in small pulmonary vessel muscularization was prevented by training. Respective counterregulatory processes were detected for the nitric oxide-soluble guanylate cyclase-phosphodiesterase system. We conclude that individualized daily exercise can prevent vascular remodeling in hypoxia-induced PH. PMID:24705723

Weissmann, Norbert; Peters, Dorothea M; Klöpping, Christina; Krüger, Karsten; Pilat, Christian; Katta, Susmitha; Seimetz, Michael; Ghofrani, Hossein A; Schermuly, Ralph T; Witzenrath, Martin; Seeger, Werner; Grimminger, Friedrich; Mooren, Frank C

2014-06-01

109

INHIBITION OF THE SDF-1/CXCR4 AXIS ATTENUATES NEONATAL HYPOXIA-INDUCED PULMONARY HYPERTENSION  

PubMed Central

Exposure of the neonatal lung to chronic hypoxia produces significant pulmonary vascular remodeling, right ventricular hypertrophy (RVH), and decreased lung alveolarization. Given recent data suggesting that stem cells could contribute to pulmonary vascular remodeling and RVH, we tested the hypothesis that blockade of stromal derived factor-1 (SDF-1), a key stem cell mobilizer or its receptor, chemokine receptor 4 (CXCR4), would attenuate and reverse hypoxia-induced cardiopulmonary remodeling in newborn mice. Neonatal mice exposed to normoxia or hypoxia were randomly assigned to receive daily intra-peritoneal injections of normal saline (PL), AMD3100, or anti-SDF-1 antibody from postnatal day 1–7 (preventative strategy) or postnatal day 7–14 (therapeutic strategy). As compared to PL, inhibition of the SDF-1/CXCR4 axis significantly improved lung alveolarization, as well as decreased pulmonary hypertension, RVH, vascular remodeling, vascular cell proliferation and lung or RV stem cell expressions to near baseline values. We therefore conclude that the SDF-1/CXCR4 axis both prevents and reverses hypoxia-induced cardiopulmonary remodeling in neonatal mice, by decreasing progenitor cell recruitment to the pulmonary vasculature as well as by decreasing pulmonary vascular cell proliferation. These data offer novel insights into the role of the SDF-1/CXCR4 axis in the pathogenesis of neonatal hypoxia-induced cardiopulmonary remodeling and have important therapeutic implications. PMID:19423843

Young, Karen C; Torres, Eneida; Hatzistergos, Konstantinos E.; Hehre, Dorothy; Suguihara, Cleide; Hare, Joshua M.

2009-01-01

110

Inhibition of the SDF-1/CXCR4 axis attenuates neonatal hypoxia-induced pulmonary hypertension.  

PubMed

Exposure of the neonatal lung to chronic hypoxia produces significant pulmonary vascular remodeling, right ventricular hypertrophy, and decreased lung alveolarization. Given recent data suggesting that stem cells could contribute to pulmonary vascular remodeling and right ventricular hypertrophy, we tested the hypothesis that blockade of SDF-1 (stromal cell-derived factor 1), a key stem cell mobilizer or its receptor, CXCR4 (CXC chemokine receptor 4), would attenuate and reverse hypoxia-induced cardiopulmonary remodeling in newborn mice. Neonatal mice exposed to normoxia or hypoxia were randomly assigned to receive daily intraperitoneal injections of normal saline, AMD3100, or anti-SDF-1 antibody from postnatal day 1 to 7 (preventive strategy) or postnatal day 7 to 14 (therapeutic strategy). As compared to normal saline, inhibition of the SDF-1/CXCR4 axis significantly improved lung alveolarization and decreased pulmonary hypertension, right ventricular hypertrophy, vascular remodeling, vascular cell proliferation, and lung or right ventricular stem cell expressions to near baseline values. We therefore conclude that the SDF-1/CXCR4 axis both prevents and reverses hypoxia-induced cardiopulmonary remodeling in neonatal mice, by decreasing progenitor cell recruitment to the pulmonary vasculature, as well as by decreasing pulmonary vascular cell proliferation. These data offer novel insights into the role of the SDF-1/CXCR4 axis in the pathogenesis of neonatal hypoxia-induced cardiopulmonary remodeling and have important therapeutic implications. PMID:19423843

Young, Karen C; Torres, Eneida; Hatzistergos, Konstantinos E; Hehre, Dorothy; Suguihara, Cleide; Hare, Joshua M

2009-06-01

111

Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension.  

PubMed

Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, ?-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH. PMID:25224369

Kolli, Madhukar B; Manne, Nandini D P K; Para, Radhakrishna; Nalabotu, Siva K; Nandyala, Geeta; Shokuhfar, Tolou; He, Kun; Hamlekhan, Azhang; Ma, Jane Y; Wehner, Paulette S; Dornon, Lucy; Arvapalli, Ravikumar; Rice, Kevin M; Blough, Eric R

2014-12-01

112

Genetic predictors of thiazide-induced serum potassium changes in nondiabetic hypertensive patients.  

PubMed

Thiazide diuretics are associated with an increased risk of hypokalemia. However, pharmacogenetic markers of thiazide-induced changes in serum potassium are not well studied. The aim of this study was to investigate possible predictors of serum potassium changes after thiazide treatment. Nondiabetic hypertensive patients with a systolic blood pressure of ?140 or a diastolic blood pressure of ?90?mm?Hg were enrolled in our study. After 2 weeks of lifestyle modification and diet instruction, patients with persistently elevated blood pressure were given 50?mg of hydrochlorothiazide every morning for 2 weeks. Twenty single-nucleotide polymorphism (SNP) markers were selected from two candidate genes, SLC12A3 and WNK1. Serum potassium levels were checked before and after hydrochlorothiazide treatment. A total of 75 patients eventually qualified for enrollment in our study. They received 50?mg of hydrochlorothiazide every morning for 2 weeks. Six SNPs in WNK1 (rs11064524, rs4980973, rs12581940, rs880054, rs953361, and rs10849582) were correlated with decreases in serum potassium. None of the SLC12A3 polymorphisms were correlated with decreases in serum potassium. After Bonferroni's correction, only rs4980973 was correlated with decreases in serum potassium (corrected P=0.014). Multivariate stepwise linear regression analysis revealed that the changes in serum potassium levels were independently associated with the baseline potassium level (?=-0.587, 95% confidence interval=-0.875--0.299, P=0.0001) and WNK1 rs4980973 (A/A and A/G vs. G/G, ?=-0.418, 95% confidence interval=-0.598--0.237, P=0.00002). In conclusion, the baseline potassium level and the WNK1 rs4980973 polymorphism were independent predictors of decreases in serum potassium after short-term hydrochlorothiazide treatment in nondiabetic hypertensive patients. PMID:24694645

Huang, Chin-Chou; Chung, Chia-Min; Hung, Shuen-Iu; Leu, Hsin-Bang; Lin, Liang-Yu; Huang, Po-Hsun; Wu, Tao-Cheng; Lin, Shing-Jong; Pan, Wen-Harn; Chen, Jaw-Wen

2014-08-01

113

Induction of heme oxygenase 1 attenuates placental ischemia-induced hypertension.  

PubMed

Recent in vitro studies have reported that heme oxygenase 1 (HO-1) downregulates the angiostatic protein soluble fms-like tyrosine kinase 1 from placental villous explants and that the HO-1 metabolites CO and bilirubin negatively regulate endothelin 1 and reactive oxygen species. Although soluble fms-like tyrosine kinase 1, endothelin 1, and reactive oxygen species have been implicated in the pathophysiology of hypertension during preeclampsia and in response to placental ischemia in pregnant rats, it is unknown whether chronic induction of HO-1 alters the hypertensive response to placental ischemia. The present study examined the hypothesis that HO-1 induction in a rat model of placental ischemia would beneficially affect blood pressure, angiogenic balance, superoxide, and endothelin 1 production in the ischemic placenta. To achieve this goal we examined the effects of cobalt protoporphyrin, an HO-1 inducer, in the reduced uterine perfusion pressure (RUPP) placental ischemia model and in normal pregnant rats. In response to RUPP treatment, mean arterial pressure increases 29 mm Hg (136±7 versus 106±5 mm Hg), which is significantly attenuated by cobalt protoporphyrin (118±5 mm Hg). Although RUPP treatment causes placental soluble fms-like tyrosine kinase 1/vascular endothelial growth factor ratios to alter significantly to an angiostatic balance (1.00±0.10 versus 1.27±0.20), treatment with cobalt protoporphyrin causes a significant shift in the ratio to an angiogenic balance (0.68±0.10). Placental superoxide increased in RUPP (952.5±278.8 versus 243.9±70.5 relative light units/min per milligram) but was significantly attenuated by HO-1 induction (482.7±117.4 relative light units/min per milligram). Also, the preproendothelin message was significantly increased in RUPP, which was prevented by cobalt protoporphyrin. These data indicate that HO-1, or its metabolites, is a potential therapeutic for the treatment of preeclampsia. PMID:21383306

George, Eric M; Cockrell, Kathy; Aranay, Marietta; Csongradi, Eva; Stec, David E; Granger, Joey P

2011-05-01

114

Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension  

PubMed Central

Microtubules are components of the cardiac cytoskeleton that can proliferate in response to pressure-overload in animal and human heart failure. We wished to test whether there was a proliferation of the microtubule cytoskeleton in the right ventricle of rats with pulmonary hypertension induced by monocrotaline (MCT) and whether this contributed to contractile dysfunction. Male Wistar rats were injected with 60 mg/kg of MCT in saline or an equivalent volume of saline (CON). MCT produced clinical signs of heart failure within 4 weeks of injection. Expression of right ventricular mRNA for ?-tubulin was measured by real-time reverse transcription polymerase chain reaction. Free and polymerised fractions of ?-tubulin protein were assessed using Western blot analysis and immunofluorescence microscopy was used to assess tyrosinated and acetylated (stabilized) microtubules. Right ventricular myocyte contraction was measured in response to the microtubule de-polymeriser colchicine (10 ?mol/l for at least 1 h). Compared to CON, in MCT right ventricles there was a small but statistically significant increase in the expression of mRNA for ?-tubulin (P < 0.001); total (P < 0.05) and polymerised fraction (P < 0.01) of ?-tubulin protein and level of acetylated tubulin (P < 0.01). However colchicine treatment did not increase the contraction of MCT myocytes (P > 0.05) or affect their response to increased stimulation frequency. Our observations support the hypothesis that microtubule proliferation is a common response to pulmonary hypertension in failing right ventricles but suggest that the effect this has on contraction depends upon the specific experimental or clinical conditions that prevail and the subsequent level of microtubule proliferation. PMID:23261965

Stones, Rachel; Benoist, David; Peckham, Michelle; White, Ed

2013-01-01

115

Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension.  

PubMed

Microtubules are components of the cardiac cytoskeleton that can proliferate in response to pressure-overload in animal and human heart failure. We wished to test whether there was a proliferation of the microtubule cytoskeleton in the right ventricle of rats with pulmonary hypertension induced by monocrotaline (MCT) and whether this contributed to contractile dysfunction. Male Wistar rats were injected with 60mg/kg of MCT in saline or an equivalent volume of saline (CON). MCT produced clinical signs of heart failure within 4weeks of injection. Expression of right ventricular mRNA for ?-tubulin was measured by real-time reverse transcription polymerase chain reaction. Free and polymerised fractions of ?-tubulin protein were assessed using Western blot analysis and immunofluorescence microscopy was used to assess tyrosinated and acetylated (stabilized) microtubules. Right ventricular myocyte contraction was measured in response to the microtubule de-polymeriser colchicine (10?mol/l for at least 1h). Compared to CON, in MCT right ventricles there was a small but statistically significant increase in the expression of mRNA for ?-tubulin (P<0.001); total (P<0.05) and polymerised fraction (P<0.01) of ?-tubulin protein and level of acetylated tubulin (P<0.01). However colchicine treatment did not increase the contraction of MCT myocytes (P>0.05) or affect their response to increased stimulation frequency. Our observations support the hypothesis that microtubule proliferation is a common response to pulmonary hypertension in failing right ventricles but suggest that the effect this has on contraction depends upon the specific experimental or clinical conditions that prevail and the subsequent level of microtubule proliferation. PMID:23261965

Stones, Rachel; Benoist, David; Peckham, Michelle; White, Ed

2013-03-01

116

Emblica officinalis Exerts Antihypertensive Effect in a Rat Model of DOCA-Salt-Induced Hypertension: Role of (p) eNOS, NO and Oxidative Stress  

Microsoft Academic Search

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone\\u000a acetate\\/1% NaCl high salt (DOCA\\/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may\\u000a influence DOCA\\/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced\\u000a in rats by DOCA-salt (20 mg\\/kg, s.c.) twice weekly for 5 weeks and replacing

Jagriti BhatiaFauzia; Fauzia Tabassum; Ashok Kumar Sharma; Saurabh Bharti; Mahaveer Golechha; Sujata Joshi; Abhay Krishna Srivastava; Dharamvir Singh Arya

2011-01-01

117

Megakaryocytic Leukemia 1 (MKL1) Regulates Hypoxia Induced Pulmonary Hypertension in Rats  

PubMed Central

Hypoxia induced pulmonary hypertension (HPH) represents a complex pathology that involves active vascular remodeling, loss of vascular tone, enhanced pulmonary inflammation, and increased deposition of extracellular matrix proteins. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator known to influence cellular response to stress signals in the vasculature. We report here that in response to chronic hypobaric hypoxia, MKL1 expression was up-regulated in the lungs in rats. Short hairpin RNA (shRNA) mediated depletion of MKL1 significantly ameliorated the elevation of pulmonary arterial pressure in vivo with a marked alleviation of vascular remodeling. MKL1 silencing also restored the expression of NO, a key vasoactive molecule necessary for the maintenance of vascular tone. In addition, hypoxia induced pulmonary inflammation was dampened in the absence of MKL1 as evidenced by normalized levels of pro-inflammatory cytokines and chemokines as well as reduced infiltration of pro-inflammatory immune cells in the lungs. Of note, MKL1 knockdown attenuated fibrogenesis in the lungs as indicated by picrosirius red staining. Finally, we demonstrate that MKL1 mediated transcriptional activation of type I collagen genes in smooth muscle cells under hypoxic conditions. In conclusion, we data highlight a previously unidentified role for MKL1 in the pathogenesis of HPH and as such lay down groundwork for future investigation and drug development. PMID:24647044

Yuan, Zhibin; Chen, Jian; Chen, Dewei; Xu, Gang; Xia, Minjie; Xu, Yong; Gao, Yuqi

2014-01-01

118

Megakaryocytic leukemia 1 (MKL1) regulates hypoxia induced pulmonary hypertension in rats.  

PubMed

Hypoxia induced pulmonary hypertension (HPH) represents a complex pathology that involves active vascular remodeling, loss of vascular tone, enhanced pulmonary inflammation, and increased deposition of extracellular matrix proteins. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator known to influence cellular response to stress signals in the vasculature. We report here that in response to chronic hypobaric hypoxia, MKL1 expression was up-regulated in the lungs in rats. Short hairpin RNA (shRNA) mediated depletion of MKL1 significantly ameliorated the elevation of pulmonary arterial pressure in vivo with a marked alleviation of vascular remodeling. MKL1 silencing also restored the expression of NO, a key vasoactive molecule necessary for the maintenance of vascular tone. In addition, hypoxia induced pulmonary inflammation was dampened in the absence of MKL1 as evidenced by normalized levels of pro-inflammatory cytokines and chemokines as well as reduced infiltration of pro-inflammatory immune cells in the lungs. Of note, MKL1 knockdown attenuated fibrogenesis in the lungs as indicated by picrosirius red staining. Finally, we demonstrate that MKL1 mediated transcriptional activation of type I collagen genes in smooth muscle cells under hypoxic conditions. In conclusion, we data highlight a previously unidentified role for MKL1 in the pathogenesis of HPH and as such lay down groundwork for future investigation and drug development. PMID:24647044

Yuan, Zhibin; Chen, Jian; Chen, Dewei; Xu, Gang; Xia, Minjie; Xu, Yong; Gao, Yuqi

2014-01-01

119

Role of vascular endothelial growth factor signaling in Schistosoma-induced experimental pulmonary hypertension  

PubMed Central

Abstract There is significant evidence that Th2 (T helper 2)-mediated inflammation supports the pathogenesis of both human and experimental animal models of pulmonary hypertension (PH). A key immune regulator is vascular endothelial growth factor (VEGF), which is produced by Th2 inflammation and can itself contribute to Th2 pulmonary responses. In this study, we interrogated the role of VEGF signaling in a murine model of schistosomiasis-induced PH with a phenotype of significant intrapulmonary Th2 inflammation, vascular remodeling, and elevated right ventricular pressures. We found that VEGF receptor blockade partially suppressed the levels of the Th2 inflammatory cytokines interleukin (IL)-4 and IL-13 in both the lung and the liver after Schistosoma mansoni exposure and suppressed pulmonary vascular remodeling. These findings suggest that VEGF positively contributes to schistosomiasis-induced vascular inflammation and remodeling, and they also provide evidence for a VEGF-dependent signaling pathway necessary for pulmonary vascular remodeling and inflammation in this model. PMID:25006448

2014-01-01

120

Effects of everolimus in combination with sildenafil in monocrotaline-induced pulmonary hypertension in rats.  

PubMed

In our study, we investigated the efficacy of everolimus in combination with sildenafil on hemodynamic and morphological parameters in rats with monocrotaline-induced pulmonary hypertension (PH). Right ventricular pressure (RVP), right ventricular hypertrophy, and the response to vasoconstrictor and vasodilator agents in pulmonary arteries as evaluated by myography and histopathological changes were compared among the groups. RVP and right ventricle/body weight ratios were increased in non-treated monocrotaline groups versus the controls; these increased ratios were decreased in the treated groups and were similar to control values. The contractile responses to endothelin-1 in the pulmonary arteries were decreased in the non-treated monocrotaline groups versus the control. In the treatment groups, contractile responses were similar to those in the controls. Responses to acetylcholine and sodium nitroprusside relaxation were decreased in non-treated monocrotaline groups but were improved significantly in the everolimus groups. Upon histopathological examination, the vascular hypertrophy and cardiac hypertrophy observed in monocrotaline groups were improved by the sildenafil and everolimus treatment. In particular, these improvements became remarkable, including the inflammatory changes, in the everolimus treatment groups. In the light of these results, sildenafil and everolimus in combination were more effective than sildenafil treatment alone in reversing the remodelling process without any cardiovascular toxic effects in the monocrotaline-induced PH model. PMID:21811847

Ilgin, Sinem; Burukoglu, Dilek; Atli, Ozlem; Sirmagul, Basar

2012-03-01

121

Hydrogen peroxide modulates phenylephrine-induced contractile response in renal hypertensive rat aorta.  

PubMed

Endothelium-derived factors play an important role in vascular tone control. This study aimed to evaluate how endothelium and reactive oxygen species (ROS) contribute to phenylephrine (PE)-induced contraction in renovascular hypertensive (2K-1C) and normotensive (2K) rats aortas. The effects of the superoxide scavenger Tiron (0.1mM and 1mM) or catalase (30 U/ml, 90 U/ml, 150 U/ml and 300 U/ml) on the PE-induced contraction were evaluated in both intact endothelium (E+) and denuded (E-) aortas. Endothelium removal increased the PE-induced contractions. The maximum contractile response decreased only in 2K-1C rat E+ aorta, and catalase (30 U/ml, 90 U/ml, 150 U/ml) partially reversed this effect. Endothelium increased the basal hydrogen peroxide (H2O2) production in 2K and 2K-1C rats aortas. PE-stimulated H2O2 production was higher in 2K-1C (E+/E-) than in 2K (E+/E-). Inhibition of the enzymes cyclooxygenase, NADPH-oxidase, xanthine-oxidase, and superoxide dismutase reduced the PE-stimulated H2O2 production in 2K-1C rat aorta. The decreased contraction to PE in 2K-1C rat aorta is partially due to endothelial H2O2 production; however, in denuded aorta, it contributes to maintaining the contractile response. Superoxide plays an important role on the PE-induced contraction in 2K rat denuded aorta, whereas in 2K-1C rat aorta, it is H2O2 that plays an important role in this effect. PMID:24091168

Silva, Bruno R; Pernomian, Laena; Grando, Marcella D; Amaral, Jefferson H; Tanus-Santos, José E; Bendhack, Lusiane M

2013-12-01

122

Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats  

PubMed Central

Objective. Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats. Methods. AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20?V) or low (5?V) voltage. Results. Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus. Discussion and Conclusion. Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR. PMID:25328683

Nagayama, Tomomi; Hirooka, Yoshitaka; Chishaki, Akiko; Takemoto, Masao; Mukai, Yasushi; Inoue, Shujiro; Kishi, Takuya; Sunagawa, Kenji

2014-01-01

123

Cilnidipine lowered psychological stress-induced increase in blood pressure in a hypertensive man: a case report  

PubMed Central

Background In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood pressure was attenuated by cilnidipine. Case Presentation The patient (a 72-year-old man) had hypertension and was on antihypertensive therapy. When mentally concentrating, he experienced occipital headaches and dizziness, and despite thorough testing, no abnormality was found. He was subsequently referred to our department. The mirror drawing test (MDT), a psychological stress test, increased blood pressure by about 40 mmHg, and the patient described occipital headache. Plasma noradrenaline level also increased from 212 to 548 pg/ml. We therefore switched the patient from nifedipine, an L-type calcium (Ca) channel blocker, to cilnidipine, an L-type/N-type Ca channel blocker with suppressive effects on sympathetic activity. Cilnipidine attenuated MDT-induced an increase in blood pressure and plasma noradrenaline level and prevented the development of headache during testing. Conclusion These findings suggest that cilnidipine is a useful antihypertensive agent for hypertensive patients in whom psychological stress causes marked fluctuations in blood pressure. PMID:17900335

Hayashida, Sota; Oka, Takakazu; Tsuji, Sadatoshi

2007-01-01

124

Different susceptibility of stress-induced gastric ulcer and the autonomic nervous function in the hereditary hypertensive rats.  

PubMed

Susceptibility of stress-induced ulcer by restraint water immersion (RWI) was examined in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). Ulcer formation was slight in SHR, and very slight in SHRSP. The ulcer index and blood pressure showed a significant inverse correlation (P < 0.001). Acid secretion was lowest in SHRSP, and hypergastrinemia was present in SHRSP. Gastric motility was suppressed during RWI in SHR and SHRSP. The noradrenaline content of the gastric mucosa and muscle layer was significantly greater in these hypertensive strains, and histologically noradrenergic innervation in the mucosa was also denser in SHRSP and SHR. Choline acetyltransferase activity in the stomach was significantly lower in SHR and SHRSP than WKY (P < 0.01). These findings suggest that susceptibility of stress-induced ulcer is inversely correlated with systemic blood pressure and that the alteration of autonomic nervous function contributes to inhibition of stress ulcers by suppressing acid secretion and motility in the hereditary hypertensive rats. PMID:8014374

Ito, M; Shichijo, K; Sekine, I; Ozaki, M

1994-03-01

125

Overexpression of VEGF-C attenuates chronic high salt intake-induced left ventricular maladaptive remodeling in spontaneously hypertensive rats.  

PubMed

Recent studies have shown that the tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway-induced lymphangiogenesis provides a buffering mechanism for high salt (HS) intake-induced elevation of blood pressure (BP). Moreover, blocking of TonEBP/VEGF-C signaling by mononuclear phagocyte depletion can induce salt-sensitive hypertension in rats. We hypothesized that HS intake could have an impact on cardiac lymphangiogenesis, and regulation of VEGF-C bioactivity, which is largely through the main receptor for VEGFR-3, may modulate HS intake-induced left ventricular remodeling. We demonstrated upregulation of TonEBP, increased macrophage infiltration, and enhanced lymphangiogenesis in the left ventricles of spontaneously hypertensive rats (SHR) that were fed a HS diet (8.0% NaCl). Then, retrovirus vectors capable of overexpression (?N?C/VEGF-C/Cys152Ser, used for overexpressing VEGF-C) and blocking (VEGFR-3-Rg, used for trapping of bioactive VEGF-C) of VEGF-C and control vector (pLPCX) were intravenously administered to SHR from week 9 of a 12-wk HS loading period. At the end of the HS challenge, overexpression of VEGF-C led to enhanced cardiac lymphangiogenesis, decreased myocardial fibrosis, and macrophage infiltration, preserved left ventricular functions, as well as decreased blood pressure level compared with the HS group and the control vector-treated HS group. In contrast, systemic blocking of VEGF-C was associated with elevation of blood pressure level and an exacerbation of hypertensive left ventricular remodeling, as indicated by increased fibrosis and macrophage infiltration, and diminished lymphangiogenesis. Hence, our findings highlight that VEGF-C/VEGFR-3 is a promising therapeutic target to attenuate hypertensive left ventricular remodeling induced by HS intake, presumably via blood pressure-dependent and -independent mechanisms. PMID:24337460

Yang, Guo-Hong; Zhou, Xin; Ji, Wen-Jie; Zeng, Shan; Dong, Yan; Tian, Lu; Bi, Ying; Guo, Zhao-Zeng; Gao, Fei; Chen, Hong; Jiang, Tie-Min; Li, Yu-Ming

2014-02-15

126

Expression of hypoxia-inducible factor-1?, endothelin-1 and adrenomedullin in newborn rats with hypoxia-induced pulmonary hypertension  

PubMed Central

Hypoxia-inducible factor (HIF)-1? is associated with hypoxia-induced pulmonary hypertension (HPH) in adults. In the present study, the expression levels of HIF-1?, endothelin (ET)-1 and adrenomedullin (ADM) were analyzed during HPH in neonates. In total, 96 newborn rats were subjected to hypoxia or normoxia for 3, 5, 7, 10, 14 or 21 days (n=8 per subgroup). HIF-1?, ET-1 and ADM expression levels were measured by quantitative polymerase chain reaction. In addition, the intima-media thickness/external diameter ratio (MT%) and medial wall cross-sectional area/vessel total cross-sectional area ratio (MA%) were calculated to evaluate pulmonary vascular remodeling. The mean pulmonary arterial pressure (mPAP) increased with exposure to hypoxia. Furthermore, the expression levels of HIF-1?, ET-1 and ADM in the lungs were shown to increase after three and five days of hypoxia, while the MT% and MA% increased after seven days of hypoxia, as compared with the controls (P<0.05). Therefore, the expression of HIF-1?, ET-1 and ADM is upregulated in the lungs of newborn rats during early HPH. At later stages, the mPAP increases, vascular remodeling occurs and HIF-1?, ET-1 and ADM expression levels restore to normal levels. PMID:24944643

WANG, LE; ZHOU, YING; LI, MINGXIA; ZHU, YANPING

2014-01-01

127

Role of Endothelin in Mediating Tumor Necrosis Factor-Induced Hypertension in Pregnant Rats  

Microsoft Academic Search

Hypertension during preeclampsia is associated with an increase in plasma levels of tumor necrosis factor (TNF)-, a cytokine known to contribute to endothelial dysfunction. Recently, our laboratory reported that a 2-fold increase in plasma TNF- produces hypertension in pregnant rats. Endothelin is also elevated in preeclampsia and endothelin synthesis is enhanced by TNF-. The purpose of this study was to

B. Babbette; D. LaMarca; Kathy Cockrell; Elizabeth Sullivan; William Bennett; Joey P. Granger

2009-01-01

128

Impairment of Executive Function Induced by Hypertension in the Rhesus Monkey (Macaca mulatta )  

Microsoft Academic Search

The effects of chronic, untreated hypertension on executive function were investigated in a nonhuman primate model of hypertensive cerebrovascular disease. Executive function was assessed with the Conceptual Set-Shifting Task (CSST), a task adapted from the human Wisconsin Card Sorting Test (WCST). Like the WCST, the CSST requires abstraction of a stimulus set, followed by a series of set shifts. Performance

Tara L. Moore; Ronald J. Killiany; Douglas L. Rosene; Somnath Prusty; William Hollander; Mark B. Moss

2002-01-01

129

Role of the TGF-b\\/Alk5 Signaling Pathway in Monocrotaline-induced Pulmonary Hypertension  

Microsoft Academic Search

Rationale: Pulmonary arterial hypertension is a progressive disease characterized by an elevation in the mean pulmonary artery pres- sure leading to right heart failure and a significant risk of death. Alterations in two transforming growth factor (TGF) signaling pathways, bone morphogenetic protein receptor II and the TGF-b receptor I, Alk1, have been implicated in the pathogenesis of pulmonary hypertension (PH).

Ari L. Zaiman; Megan Podowski; Satya Medicherla; Kimberley Gordy; Fang Xu; Lijie Zhen; Larissa A. Shimoda; Enid Neptune; Linda Higgins; Alison Murphy; Sarvajit Chakravarty; Andrew Protter; Pravin B. Sehgal; Hunter C. Champion; Rubin M. Tuder

2008-01-01

130

Beneficial effects of combination of valsartan and amlodipine on salt-induced brain injury in hypertensive rats.  

PubMed

The optimum antihypertensive treatment for prevention of hypertensive stroke has yet to be elucidated. This study was undertaken to examine the benefit of a combination of valsartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, in prevention of high-salt-induced brain injury in hypertensive rats. High-salt-loaded stroke-prone spontaneously hypertensive rats (SHRSPs) were given 1) vehicle, 2) valsartan (2 mg/kg/day), 3) amlodipine (2 mg/kg/day), or 4) a combination of valsartan and amlodipine for 4 weeks. The effects on brain injury were compared between all groups. High-salt loading in SHRSPs caused the reduction of cerebral blood flow (CBF), cerebral hypoxia, white matter lesions, glial activation, AT1 receptor up-regulation, endothelial nitric-oxide synthase (eNOS) uncoupling, inducible nitric-oxide synthase induction, and nitroxidative stress. Valsartan, independently of blood pressure, enhanced the protective effects of amlodipine against brain injury, white matter lesions, and glial activation in salt-loaded SHRSPs. These beneficial effects of valsartan added to amlodipine were associated with an additive improvement in CBF and brain hypoxia because of an additive improvement in cerebral arteriolar remodeling and vascular endothelial dysfunction. Furthermore, valsartan added to amlodipine enhanced the attenuation of cerebral nitroxidative stress through an additive suppression of eNOS uncoupling. Valsartan, independently of blood pressure, augmented the protective effects of amlodipine against brain injury in salt-loaded hypertensive rats through an improvement in brain circulation attributed to nitroxidative stress. Our results suggest that the combination of valsartan and amlodipine may be a promising strategy for the prevention of salt-related brain injury in hypertensive patients. PMID:21807884

Dong, Yi-Fei; Kataoka, Keiichiro; Tokutomi, Yoshiko; Nako, Hisato; Nakamura, Taishi; Toyama, Kensuke; Sueta, Daisuke; Koibuchi, Nobutaka; Yamamoto, Eiichiro; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2011-11-01

131

Hypertensive Crisis  

MedlinePLUS

... these levels is critical to determine the appropriate management. Hypertensive Emergency A hypertensive emergency exists when blood pressure reaches levels that are damaging organs. Hypertensive emergencies generally occur ...

132

Gene therapy strategies in glaucoma and application for steroid-induced hypertension  

PubMed Central

Gene therapy of the eye has a high potential of becoming the preferred treatment of a number of eye diseases. Because of its easy accessibility, all the tissues of the eye can be reached and genetically manipulated with nowadays standard gene delivery technologies. Gene therapy offers the possibility to do both, correct a genetic defect by replacing the mutated or missing gene and that of using genes as drugs. Gene drugs would be more specific and would have a longer duration of action and less toxicity than conventional drugs. Examples of both applications are beginning to emerge. Using gene replacement, vision has been restored in several patients of Leber congenital amaurosis (Maguire et al., 2009). Some gene drugs, such as siRNA, are currently in clinical trials to silence angiogenic factors in macular degeneration (Campa and Harding, 2011). In this manuscript we first give a short overview of the basics of gene therapy in the eye and then review the ongoing preclinical studies in our laboratory for the gene-drug treatment of steroid-induced ocular hypertension. PMID:23960949

Borrás, Teresa

2011-01-01

133

Sleep and Pregnancy-Induced Hypertension: A Possible Target for Intervention?  

PubMed Central

Sleep disturbances in the general population are associated with elevated blood pressure. This may be due to several mechanisms, including sympathetic activation and hypothalamic-pituitary-adrenal (HPA) axis disturbance. Elevated blood pressure in pregnancy can have devastating effects on both maternal and fetal health and is associated with increased risk for preeclampsia and poor delivery outcomes. Preliminary evidence suggests that mechanisms linking sleep and blood pressure in the general population may also hold in the pregnant population. However, the effects of disturbed sleep on physiologic mechanisms that may directly influence blood pressure in pregnancy have not been well studied. The role that sleep disturbance plays in gestational blood pressure elevation and its subsequent consequences warrant further investigation. This review evaluates the current literature on sleep disturbance and elevated blood pressure in pregnancy and proposes possible treatment interventions. Citation: Haney A; Buysse DJ; Okun M. Sleep and pregnancy-induced hypertension: a possible target for intervention? J Clin Sleep Med 2013;9(12):1349-1356. PMID:24340300

Haney, Alyssa; Buysse, Daniel J.; Okun, Michele

2013-01-01

134

Carotid Body Denervation Prevents the Development of Insulin Resistance and Hypertension Induced by Hypercaloric Diets  

PubMed Central

Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT). The carotid bodies (CB) are peripheral chemoreceptors that classically respond to hypoxia by increasing chemosensory activity in the carotid sinus nerve (CSN), causing hyperventilation and activation of the sympathoadrenal system. Besides its role in the control of ventilation, the CB has been proposed as a glucose sensor implicated in the control of energy homeostasis. However, to date no studies have anticipated its role in the development of IR. Herein, we propose that CB overstimulation is involved in the etiology of IR and HT, core metabolic and hemodynamic disturbances of highly prevalent diseases like the metabolic syndrome, type 2 diabetes, and obstructive sleep apnoea. We demonstrate that CB activity is increased in IR animal models and that CSN resection prevents CB overactivation and diet-induced IR and HT. Moreover, we show that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB overactivation. We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases. PMID:23530003

Ribeiro, Maria J.; Sacramento, Joana F.; Gonzalez, Constancio; Guarino, Maria P.; Monteiro, Emilia C.; Conde, Silvia V.

2013-01-01

135

Cold-restraint induced gastric lesions in normotensive and spontaneously hypertensive rats  

SciTech Connect

Spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats were subjected to 2 hr of cold-restraint stress at 4-6/sup o/C following a 24 hr fast. WKY rats had a significantly greater incidence and degree of ulceration of the gastric glandular mucosa than did SHR rats. Mean arterial pressure, obtained from a chronic arterial cannula, fell during 2 hr of cold-restraint stress in both SHR and WKY rats. Heart rate was unchanged in WKY but fell significantly in SHR. Plasma norepinephrine (NE) and epinephrine (E), determined by radioenzymatic assay, increased significantly following stress. Increased levels of NE remained similar for both SHR and WKY rats, while post-stress levels of E for the SHR rats greatly exceeded E levels for WKY rats. A greater degree of hypothermia was also noted in SHR rats. Decreased stress induced ulcerogenesis in the SHR may be due to the well-known altered hemodynamic and autonomic nervous system reactivity in this strain or other factors not yet discovered.

Athey, G.R.; Iams, S.G.

1981-02-23

136

Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension.  

PubMed

Our previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) can inhibit the progression of pulmonary artery hypertension (PAH) in the monocrotaline (MCT) model in the short term. The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation. PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study. Postoperatively, the animals were randomly divided into three groups (n = 10 in each group): control, PAH group, and BMSCs implantation group. Six months after injection, immunology and immunohistochemistry analysis indicated the MCT-induced intima-media thickness in muscular arteries was reduced (P < 0.05); the area of collagen fibers in lung tissue was lower (P < 0.05), and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased (P < 0.05). Immunofluorescence showed that the cells have the ability to differentiate between von Willebrand factor and vascular endothelial growth factor. Six months after intravenous injection, BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation. PMID:23996433

Luan, Yun; Zhang, Xue; Qi, Tong-Gang; Cheng, Guang-Hui; Sun, Chao; Kong, Feng

2014-11-01

137

Altered lymphatic function and architecture in salt-induced hypertension assessed by near-infrared fluorescence imaging  

NASA Astrophysics Data System (ADS)

The lymphatic system plays an important role in maintaining the fluid homeostasis between the blood vascular and interstitial tissue compartment and there is recent evidence that its transport capabilities may regulate blood pressure in salt-induced hypertension. Yet, there is little known how the lymphatic contractile function and architecture responds to dietary salt-intake. Thus, we longitudinally characterized lymphatic contractile function and vessel remodeling noninvasively using dynamic near-infrared fluorescence imaging in animal models of salt-induced hypertension. The lymphatics of mice and rats were imaged following intradermal injection of indocyanine green to the ear tip or the base of the tail before and during two weeks of either a high salt diet (HSD) or normal chow. Our noninvasive imaging data demonstrated dilated lymphatic vessels in the skin of mice and rats on a HSD as compared to their baseline levels. In addition, our dynamic imaging results showed increased lymphatic contraction frequency in HSD-fed mice and rats. Lymphatic contractile function and vessel remodeling occurs in response to salt-induced hypertension suggesting a possible role for the lymphatics in the regulation of vascular blood pressure.

Kwon, Sunkuk; Agollah, Germaine D.; Chan, Wenyaw; Sevick-Muraca, Eva M.

2012-08-01

138

[Effect of captopril on hypoxia-induced pulmonary hypertension in pigs].  

PubMed

The role of angiotensin system in the development of hypoxic pulmonary hypertension, in nine pigs (50 +/- 8 kg) were studied. A Swan-Ganz Catheter and an arterial catheter were inserted into the pulmonary artery and aorta, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), Cardiac output (CO) and arterial blood gases were monitored before and after hypoxia and captopril injection (7.3 mg/kg.iv). Plasma renin activity (PRA) and angiotensin II (AT-II) were measured by RIA. Angiotensin converting enzyme (ACE) was measured by fluorometry. Results showed that during hypoxemia (PaO2 6.3 +/- 0.2 kPa, PaCO2 5.4 +/- 0.2 kPa), PAP increased from 2.43 +/- 0.17 to 3.76 +/- 0.2 kPa, (P less than 0.05) and right ventricle stroke work index (BVSWI) from 55.7 +/- 7.2 to 91.3 +/- 9.3 mJ/m2 (P less than 0.05). PRA increased from 0.56 +/- 0.19 to 1.28 +/- 6.30 mol. L-1/h (P less than 0.02) and AT-II from 62.4 +/- 17.4 to 133.3 +/- 31.8 ng/L (P less than 0.01); but ACE decreased from 77.6 +/- 5.6 to 58.4 +/- 4.2 mumol.min-1/L (P less than 0.02). After Captopril injection ACE was reduced to 26.7 +/- 3.4 mumol.min-1/L (P less than 0.001) and AT-II dropped to 61.9 +/- 15.5 ng/L (P less than 0.01), as compared with those during hypoxemia. There was significant correlation between PAP and PRA (r = 0.5643 P less than 0.01). We surmise that angiotensin system may play a part in acute hypoxia-induced pulmonary hypertension, and captopril Inhibits AT-II, leading to the drop of pulmonary arterial pressure. PMID:1648428

Chen, S

1991-03-01

139

Role of copper transport protein antioxidant 1 in angiotensin II-induced hypertension: a key regulator of extracellular superoxide dismutase.  

PubMed

Extracellular superoxide dismutase (SOD3) is a secretory copper enzyme involved in protecting angiotensin II (Ang II)-induced hypertension. We found previously that Ang II upregulates SOD3 expression and activity as a counterregulatory mechanism; however, underlying mechanisms are unclear. Antioxidant 1 (Atox1) is shown to act as a copper-dependent transcription factor, as well as a copper chaperone, for SOD3 in vitro, but its role in Ang II-induced hypertension in vivo is unknown. Here we show that Ang II infusion increases Atox1 expression, as well as SOD3 expression and activity, in aortas of wild-type mice, which are inhibited in mice lacking Atox1. Accordingly, Ang II increases vascular superoxide production, reduces endothelium-dependent vasodilation, and increases vasoconstriction in mesenteric arteries to a greater extent in Atox1(-/-) than in wild-type mice. This contributes to augmented hypertensive response to Ang II in Atox1(-/-) mice. In cultured vascular smooth muscle cells, Ang II promotes translocation of Atox1 to the nucleus, thereby increasing SOD3 transcription by binding to Atox1-responsive element in the SOD3 promoter. Furthermore, Ang II increases Atox1 binding to the copper exporter ATP7A, which obtains copper from Atox1, as well as translocation of ATP7A to plasma membranes, where it colocalizes with SOD3. As its consequence, Ang II decreases vascular copper levels, which is inhibited in Atox1(-/-) mice. In summary, Atox1 functions to prevent Ang II-induced endothelial dysfunction and hypercontraction in resistant vessels, as well as hypertension, in vivo by reducing extracellular superoxide levels via increasing vascular SOD3 expression and activity. PMID:22753205

Ozumi, Kiyoshi; Sudhahar, Varadarajan; Kim, Ha Won; Chen, Gin-Fu; Kohno, Takashi; Finney, Lydia; Vogt, Stefan; McKinney, Ronald D; Ushio-Fukai, Masuko; Fukai, Tohru

2012-08-01

140

The effects of thromboxane receptor antagonists on oestrogen-induced uterotrophic responses in the spontaneously hypertensive rat.  

PubMed Central

1. The possible role of thromboxane in the uterotrophic response to oestrogen, in the spontaneously hypertensive rat was investigated by use of the thromboxane receptor antagonists EP092, AH23848 and BM 13.505. 2. The parameters studied were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights and the concentrations of cytosolic and nuclear oestrogen receptors. 3. The antagonists attenuated oestradiol-induced uterine blood flow and significantly reduced both wet and dry uterine weight. These changes were accompanied by decreases in nuclear oestrogen receptor levels. 4. The results suggest a supportive role for thromboxane in oestradiol-induced uterine growth. PMID:1832065

Kerr, M. B.; Marshall, K.; Senior, J.

1991-01-01

141

Blood volume increase in salt-induced pulmonary hypertension, heart failure and ascites in broiler and White Leghorn chickens.  

PubMed Central

In this study we tested the hypothesis that excess dietary salt produces an expansion of extracellular fluid volume which may be associated with pulmonary hypertension-induced right ventricular failure in chickens with rapid growth rates. One-week-old broiler and White Leghorn chickens were given 0.5% salt in their drinking water for three weeks. Saline water had a minimal effect on White Leghorns. The hypothesis appears to be correct since salt-treatment in broilers resulted in up to 30% expansion in blood volume and there was 50% mortality from pulmonary hypertension-induced right ventricular failure and ascites. There was marked (up to 88% in some broilers) right ventricular hypertrophy, an indicator of pulmonary hypertension. There was less left ventricular hypertrophy as shown by an increase in the ratio of the right to total ventricle weight. There was up to 32% decrease in growth rate. There was renal hypertrophy in the salt-treated birds as shown by a higher kidney to body weight ratio. PMID:8490804

Mirsalimi, S M; O'Brien, P J; Julian, R J

1993-01-01

142

Supplementation of DETA/NO attenuates cold stress induced pulmonary hypertension syndrome in broilers  

E-print Network

The anatomical and physiological structure of avians increases the broiler chicken's susceptibility to pulmonary hypertension syndrome (PHS). This has been a continual problem in the poultry industry costing millions of dollars annually. Studies...

Thompson, Michel Ann

2012-06-07

143

Effects of 17-Hydroxyprogesterone on Tumor Necrosis Factor-?-Induced Hypertension During Pregnancy  

Microsoft Academic Search

BackgroundInflammatory cytokines such as tumor necrosis factor-? (TNF-?) may be an important link between placental ischemia and hypertension in preeclampsia. We examined the effect of 17-hydroxyprogesterone caproate (17-OHP) on TNF-?-stimulated endothelin (ET) production and hypertension during pregnancy.MethodsTNF-?-stimulated ET was examined from endothelial cells cultured in the presence and absence of progesterone. Blood pressure and tissue ET-1 were measured in the

Sharon D. Keiser; Edward W. Veillon; Marc R. Parrish; William Bennett; Kathy Cockrell; Lillian Fournier; Joey P. Granger; James N. Martin; Babbette Lamarca

2009-01-01

144

Effect of grape seed extract on lead induced hypertension and heart rate in rat.  

PubMed

The main objective of this study was to evaluate the potential protective effect of red Grape Seed Extract (GSE) on lead induced hypertension (HTN) and Heart Rate (HR) in male Wistar rats. The rats were randomly assigned to one of 4 groups: Each group received lead acetate (100 ppm in drinking water), GSE (100 mg kg(-1), orally) or Lead + GSE for 45 days. Another group assigned as control group provided with tap water and regular pellet food. The Systolic Blood Pressure (SBP) and heart rate were determined by tail plethysmography coupled to a computer system. There was a sustained elevation of SBP in lead exposed rats that significantly increased at day 18 (lead treated, 112.7 +/- 2.7 mmHg, vs. control, 105.6 +/- 2.6 mmHg, n = 10, p < 0.05) and reached a maximum level at day 36 (lead treated, 124.9 +/- 2.3 mmHg, vs. control, 103.6 +/- 3.1 mmHg, n = 10, p < 0.001). However, the other three groups; showed no significant changes in SBP. Furthermore, the heart rate was increased sustainly in lead exposed animals that was statistically significant at days 36 and 45 (lead treated group, 404.5 +/- 9.4 vs. control group, 381.7 +/- 6.7, n = 10, p < 0.05). The blood lead level in both lead and lead + GSE treated groups was increased significantly compared with control and GSE treated groups (p < 0.001). However, GSE administration had no effect on the blood lead level in lead treated group. According to the result of this study, it may be concluded that GSE could have beneficial effect in protecting the cardiovascular system through its antioxidant activity against oxidative stress. PMID:18814650

Badavi, Mohammad; Mehrgerdi, Fatemeh Zarea; Sarkaki, Alireza; Naseri, Mohammad Kazem Gharib; Dianat, Mahin

2008-03-15

145

Vanillic acid: A potential inhibitor of cardiac and aortic wall remodeling in l-NAME induced hypertension through upregulation of endothelial nitric oxide synthase.  

PubMed

The objective of the present study is to investigate the effects of vanillic acid on blood pressure, cardiac marker enzymes, left ventricular function and endothelial nitric oxide synthase (eNOS) expression in N(?)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), heart rate, cardiac marker enzymes and organ weight were increased. Impaired left ventricular function and decreased aortic eNOS expression was also observed in hypertensive rats. Moreover, treatment with vanillic acid exhibited beneficial effect on blood pressure, left ventricular function and cardiac marker enzymes. In addition, treatment with vanillic acid on hypertensive rats had upregulated eNOS expression and showed beneficial effects evidenced by histopathology and ultrastructural observations of aorta. In conclusion, vanillic acid has enough potential to normalize hypertension and left ventricular function in l-NAME induced hypertensive rats. With additional studies, vanillic acid might be used as a functional drug or as an adjuvant in the management of hypertension. PMID:25218092

Kumar, Subramanian; Prahalathan, Pichavaram; Raja, Boobalan

2014-09-01

146

Intravenous pentoxifylline does not affect the exercise-induced pulmonary arterial, capillary or venous hypertension in Thoroughbred horses.  

PubMed

The present study was carried out to examine whether intravenously administered pentoxifylline-a phosphodiesterase inhibitor which increases red blood cell deformability and decreases blood viscosity-would attenuate the magnitude of exercise-induced pulmonary capillary hypertension in healthy, fit Thoroughbred horses and in turn, diminish the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. Hemodynamic data were collected at rest, and during exercise performed at 8 and 14 m/sec on 3.5% uphill grade in the control (no medications) and the pentoxifylline (8.5 mg/kg, i.v.) experiments. The sequence of treatments was randomized for every horse and 7 days were allowed between treatments. Galloping at 14 m/sec on 3.5% uphill grade elicited maximal heart rate. In both treatments, simultaneous measurements of phasic and mean right atrial and pulmonary arterial, capillary and wedge pressures were made using catheter-tip-manometers whose signals were carefully referenced at the point of the left shoulder. In the control study, exercise resulted in progressive significant increments in heart rate, right atrial and pulmonary arterial, capillary and venous pressures; thereby, confirming that exercising Thoroughbreds develop significant pulmonary hypertension. All horses experienced exercise-induced pulmonary hemorrhage (EIPH) in the control experiments. Pentoxifylline administration to standing horses caused anxiety, tachycardia, muscular fasciculations/tremors and mild sweating, but statistically significant changes in right atrial and pulmonary arterial, capillary and venous pressures were not detected. Exercise in the pentoxifylline treatment also resulted in progressive significant increments in heart rate and right atrial as well as pulmonary vascular pressures, but these data were not statistically significantly different from those in the control study and the incidence of EIPH remained unchanged. Thus, it was concluded that i.v. pentoxifylline is ineffective in attenuating the exercise-induced pulmonary arterial, capillary and venous hypertension in healthy, fit Thoroughbred horses. PMID:11107006

Manohar, M; Goetz, T E; Rothenbaum, P; Humphrey, S

2000-10-01

147

Hypertension and oral contraceptives.  

PubMed

Large prospective epidemiologic studies have shown that long-term use of oral contraceptives containing estrogen induce an increase in blood pressure and sharply increase the risk of hypertension. Susceptibility to the hypertensive effects of oral contraceptives is heightened where risk factors such as age, family history of hypertension, preexisting or occult renal disease, parity and obesity exist. Hypertension among pill users usually develops within the first 6 months of usage and occasionally is delayed for as long as 6 years. Anitihypertensive therapy is seldom needed as the hypertension that developes is generally mild and uncomplicated, and rapidly reverses when the pills are discontinued. However, a small percentage of patients develop severe, even life-threatening hypertension and the hypertensive effects are felt long after the pills are discontinued. Cases of malignant hypertension and irreversible renal failure requiring maintenance hemodialysis, bilateral nephrectomy, and renal transplantation have occurred following administration of oral contraceptive pills. The mechanism by which oral pills induce hypertension in susceptible women is not known and needs further research. Before oral contraceptives are prescribed, physicians should take a careful history and perform a detailed physicial examination with special attention to the cardiovascular system. Multiple blood pressure measurements should be made and routine laboratory studies including urinalysis, blood urea and nitrogen and serum creatinine should be performed. It is preferable to start with a relatively low (50 mcg) estrogenic content preparation. Patients who develop hypertension (diastolic pressure, 90 mm Hg) on oral contraceptives should stop taking the pills immediately, and should be considered to have estrogen-induced hypertension. They should never again receive estrogen-containing oral pills, although they can try pills containing only progestogen. There is no contraindication to pregnancy in these patients, as most women who become hypertensive on oral pills go on to have normotensive pregnancies. Pregnancy in women who are susceptible to essential hypertension however should be treated as high risk. PMID:12263383

Oparil, S

1981-04-01

148

Oxidative stress-dependent activation of collagen synthesis is induced in human pulmonary smooth muscle cells by sera from patients with scleroderma-associated pulmonary hypertension  

PubMed Central

Pulmonary arterial hypertension is a major complication of systemic sclerosis. Although oxidative stress, intima hyperplasia and a progressive vessel occlusion appear to be clearly involved, the fine molecular mechanisms underpinning the onset and progression of systemic sclerosis-associated pulmonary arterial hypertension remain largely unknown. Here we shows for the first time that an increase of NADPH-derived reactive oxygen species production induced by sera from systemic sclerosis patients with pulmonary arterial hypertension drives collagen type I promoter activity in primary human pulmonary artery smooth muscle cells, suggesting that antioxidant-based therapies should be considered in the treatment of systemic sclerosis-associated vascular diseases. PMID:25085432

2014-01-01

149

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.  

PubMed Central

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity. PMID:1379615

Arnal, J F; Warin, L; Michel, J B

1992-01-01

150

Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats.  

PubMed

This study was designed to explore the role of losartan, an angiotensin II receptor blocker, in hypertensive injuries of blood vessels and the potential mechanisms related to the vascular advanced glycosylation end product (AGE)/receptor (RAGE) system, oxidative stress and endothelial proinflammatory factors. Spontaneously hypertensive rats (SHR) were employed for our study, and age-matched Wistar-Kyoto rats (WKY) were used for control experiments. After losartan treatment for 12 weeks, we observed by immunofluorescence that the vascular AGE level in the losartan group was significantly lower than that of the SHR group and that the vascular mRNA expression of RAGE, NF-kappaB, NADPH oxidase p47phox and ET-1, as detected by RT-PCR, was significantly lower in losartan group than in the SHR group. Meanwhile, we found that the expression of RAGE and NF-kappaB proteins in the losartan group and the WKY group was remarkably lower than that of the SHR group. Compared with the SHR group, the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the NO level were robustly increased, while the plasma malondialdehyde (MDA) and ET-1 were substantially reduced. These findings suggest that losartan decreases the vascular AGE level, suppresses RAGE and NF-kappaB activation, and enhances the antioxidant capacity thereby improving the endothelial function, which induce hypertensive vascular remodeling. PMID:17487457

Zhu, Wei-Wei; Liu, Xue-Ping; Wu, Nan; Zhao, Ting-Ting; Zhao, Yong; Zhang, Jie; Shao, Jian-Hua

2007-10-01

151

Comparison of the effect of inhaled nitric oxide and intravenous nitroglycerine on hypoxia-induced pulmonary hypertension in pigs.  

PubMed

Pulmonary hypertension is usually treated with intravenous (i.v.) vasodilators, but their use is limited by systemic effects. In the current study, we compared the effects of inhaled nitric oxide and intravenous nitroglycerine on pulmonary and systemic haemodynamic responses as well as on gas exchange measurements in anaesthetized pigs whose pulmonary pressure was increased by hypoxia (FiO2 = 15%). Both treatments reduced pulmonary pressure to the control level. Inhaled nitric oxide did not affect systemic arterial pressure but intravenous nitroglycerine decreased it from 126.2 to 108.8 mmHg (P = 0.04). Unlike intravenous nitroglycerine, inhaled nitric oxide increased arterial PaO2 from 5.3 to 5.9 kPa (P = 0.02). Both treatments diminished central venous pressure and left atrial pressure, suggesting a possible cardiac effect. Inhaled nitric oxide was shown to be a potent pulmonary vasodilator which attenuated pulmonary hypertension and improved arterial oxygenation without important direct effects on systemic pressure in porcine hypoxia-induced pulmonary hypertension. PMID:8889430

Troncy, E; Jacob, E; da Silva, P; Ducruet, T; Collet, J P; Salazkin, I; Charbonneau, M; Blaise, G

1996-09-01

152

Ameliorative Effect of Hydroethanolic Leaf Extract of Byrsocarpus coccineus in Alcohol- and Sucrose-Induced Hypertension in Rats  

PubMed Central

Hypertension remains a major health problem worldwide considering the prevalence of morbidity and mortality. Plants remain a reliable source of efficacious and better tolerated drugs and botanicals. This study was designed to investigate the effect of the chemo-profiled hydroethanolic leaf extract of Byrsocarpus coccineus in ethanol- and sucrose-induced hypertension. Groups of rats were treated orally (p.o.) with distilled water (10 ml/kg), ethanol (35%; 3 g/kg), sucrose (5-7%), and B. coccineus (100, 200, and 400 mg/kg), and nifedipine together with ethanol and sucrose separately for 8 weeks. At the end of the treatment period, blood pressure and heart rate of rats were determined. Blood was collected for serum biochemical parameters and lipid profile assessment, and the liver, aorta, kidney, and heart were harvested for estimation of in vivo antioxidants and malondialdehyde (MDA). Results obtained in this study showed that B. coccineus at the various doses administered reduced the systolic, diastolic, and arterial blood pressure elevated by ethanol and sucrose. Also, the extract reversed the reduction in catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) induced by ethanol and sucrose. The level of MDA was reduced compared to the ethanol- and sucrose-induced hypertensive group. With respect to lipid profile, administration of B. coccineus at the various doses reduced the levels of triglycerides, low-density lipoprotein (LDL), cholesterol, and atherogenic indices, compared to the ethanol and sucrose groups. In conclusion the hydroethanolic leaf extract of B. coccineus exerted significant antihypertensive effect and this is probably related to the antioxidant property and improvement of lipid profile observed in this study. PMID:25161923

Akindele, Abidemi J.; Iyamu, Endurance A.; Dutt, Prabhu; Satti, Naresh K.; Adeyemi, Olufunmilayo O.

2014-01-01

153

Ameliorative Effect of Hydroethanolic Leaf Extract of Byrsocarpus coccineus in Alcohol- and Sucrose-Induced Hypertension in Rats.  

PubMed

Hypertension remains a major health problem worldwide considering the prevalence of morbidity and mortality. Plants remain a reliable source of efficacious and better tolerated drugs and botanicals. This study was designed to investigate the effect of the chemo-profiled hydroethanolic leaf extract of Byrsocarpus coccineus in ethanol- and sucrose-induced hypertension. Groups of rats were treated orally (p.o.) with distilled water (10 ml/kg), ethanol (35%; 3 g/kg), sucrose (5-7%), and B. coccineus (100, 200, and 400 mg/kg), and nifedipine together with ethanol and sucrose separately for 8 weeks. At the end of the treatment period, blood pressure and heart rate of rats were determined. Blood was collected for serum biochemical parameters and lipid profile assessment, and the liver, aorta, kidney, and heart were harvested for estimation of in vivo antioxidants and malondialdehyde (MDA). Results obtained in this study showed that B. coccineus at the various doses administered reduced the systolic, diastolic, and arterial blood pressure elevated by ethanol and sucrose. Also, the extract reversed the reduction in catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) induced by ethanol and sucrose. The level of MDA was reduced compared to the ethanol- and sucrose-induced hypertensive group. With respect to lipid profile, administration of B. coccineus at the various doses reduced the levels of triglycerides, low-density lipoprotein (LDL), cholesterol, and atherogenic indices, compared to the ethanol and sucrose groups. In conclusion the hydroethanolic leaf extract of B. coccineus exerted significant antihypertensive effect and this is probably related to the antioxidant property and improvement of lipid profile observed in this study. PMID:25161923

Akindele, Abidemi J; Iyamu, Endurance A; Dutt, Prabhu; Satti, Naresh K; Adeyemi, Olufunmilayo O

2014-07-01

154

Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function.  

PubMed

Loss of endothelial cell-derived nitric oxide (NO) in hypertension is a hallmark of arterial dysfunction. Experimental hypertension created by the removal of NO, however, involves mechanisms in addition to decreased arterial vasodilator activity. These include augmented endothelin-1 (ET-1) release, increased sympathetic nervous system activity, and elevated tissue oxidative stress. We hypothesized that increased venous smooth muscle (venomotor) tone plays a role in Nomega-nitro-L-arginine (LNNA) hypertension through these mechanisms. Rats were treated with the NO synthase inhibitor LNNA (0.5 g/L in drinking water) for 2 weeks. Mean arterial pressure of conscious rats was 119 +/- 2 mm Hg in control and 194 +/- 5 mm Hg in LNNA rats (P<0.05). Carotid arteries and vena cava were removed for measurement of isometric contraction. Maximal contraction to norepinephrine was modestly reduced in arteries from LNNA compared with control rats whereas the maximum contraction to ET-1 was significantly reduced (54% control). Maximum contraction of vena cava to norepinephrine (37% control) also was reduced but no change in response to ET-1 was observed. Mean circulatory filling pressure, an in vivo measure of venomotor tone, was not elevated in LNNA hypertension at 1 or 2 weeks after LNNA. The superoxide scavenger tempol (30, 100, and 300 micromol kg(-1), IV) did not change arterial pressure in control rats but caused a dose-dependent decrease in LNNA rats (-18 +/- 8, -26 +/- 15, and -54 +/- 11 mm Hg). Similarly, ganglionic blockade with hexamethonium caused a significantly greater fall in LNNA hypertensive rats (76 +/- 9 mm Hg) compared with control rats (35 +/- 10 mm Hg). Carotid arteries, vena cava, and sympathetic ganglia from LNNA rats had higher basal levels of superoxide compared with those from control rats. These data suggest that while NO deficiency increases oxidative stress and sympathetic activity in both arterial and venous vessels, the impact on veins does not make a major contribution to this form of hypertension. PMID:16810074

Thakali, Keshari M; Lau, Yanny; Fink, Gregory D; Galligan, James J; Chen, Alex F; Watts, Stephanie W

2006-06-01

155

Protective effect of a JNK inhibitor against retinal ganglion cell loss induced by acute moderate ocular hypertension  

PubMed Central

Purpose To correlate retinal ganglion cell (RGC) loss and optic nerve (ON) damage with the duration of acute glaucoma attacks in a rat experimental model and to determine whether the c-Jun N-terminal kinase (JNK) inhibitor SP600125 protects against such attacks. Methods To model an acute glaucoma attack, rat intraocular pressure (IOP) was elevated by a controllable compression method using pulleys and specific weights. Intraocular pressure was measured with a TonoLab® rebound tonometer. Time-dependent ocular hypertension-induced damage was evaluated by ON morphology, retina morphology (both retina layer thickness in cross-sections and RGC counts in Dextran tetramethylrhodamine crystals [DTMR] labeled flatmounts), and scotopic flash electroretinography (ERG). A c-Jun N-terminal kinase (JNK) inhibitor, SP600125 (0, 1.5, 5, or 15 mg/kg), was administered by intraperitoneal injection immediately before and after induction of ocular hypertension, then once daily for seven days. Retinal cross-sections were measured to determine the thickness of various retinal layers and the cell density in the ganglion cell layer (GCL). Retinal flatmounts immunolabeled with anti-rat Brn-3a primary antibody were used to quantify RGC numbers. Results Elevated rat IOP induced by corneal limbus compression correlated with the different weights. Elevation to 45 mmHg for up to 7 h did not significantly affect the thicknesses of the outer nuclear layer, outer plexiform layer, or inner nuclear layer. Amplitudes of A- and B-waves were not affected. However, elevation to 45 mmHg for up to 7 h decreased the inner retinal thickness and caused ON damage. Most importantly, IOP elevation induced a time-dependent RGC loss. Cell density in the GCL decreased to 70%, 62%, and 49% of that of the control after 5 h, 6 h, and 7 h, respectively, of pressure increases. In retinal flatmount studies, labeled RGCs were reduced 56±4% (mean±SEM) versus the control (p<0.001) after 7 h of ocular hypertension. SP600125 dose-dependently protected against ocular hypertension-induced RGC loss. The difference in RGC density between the vehicle and SP600125-treated (15 mg/kg) groups was statistically significant (p<0.001). Conclusions The correlation of inner retinal morphological changes with the duration of the application of 45 mmHg IOP was demonstrated. Treatment with SP600125 significantly protected RGC survival against this insult. Inhibitors of JNK may be an interesting pharmacological class for treating glaucoma. PMID:21527996

Sun, Hui; Wang, Ying; Pang, Iok-Hou; Shen, Jiaquan; Tang, Xia; Li, Ying; Liu, Chuanyong

2011-01-01

156

Impaired Adaptive Cytoprotection to Ethanol-Induced Damage in Gastric Mucosa of Portal Hypertensive Rats  

Microsoft Academic Search

Portal hypertension predisposes gastric mucosato increased damage by noxious agents. Adaptivecytoprotection has not been studied in portalhypertensive gastric mucosa. We evaluated adaptivecytoprotection in the gastric mucosa of portal hypertensiverats by exposure to ethanol. The injury index (percentgross lesions) was significantly higher in portalhypertensive rats than in sham-operated rats. The ratio of adaptive cytoprotection, calculated as thedegree of decrease in the

Koichi Ninomiya; Seigo Kitano; Takanori Yoshida; Toshio Bandoh; Dolgor Baatar; Sadaki Tsuboi

1999-01-01

157

Nitric Oxide Deficiency in Fenfluramine and Dexfenfluramine-induced Pulmonary Hypertension  

Microsoft Academic Search

Dexfenfluramine and fenfluramine greatly increase the risk of developing pulmonary hypertension (PHT). The mechanism of anorexigen-associated PHT (AA-PHT) and the reason PHT occurs in a mi- nority of people exposed are unknown. Anorexigens are weak pulmonary vasoconstrictors, but they become potent when synthesis of the endogenous vasodilator nitric oxide (NO) is suppressed. We hypothesized NO deficiency predisposes affected individuals to

STEPHEN L. ARCHER; KHIER DJABALLAH; MARC HUMBERT; E. KENNETH WEIR; MURIEL FARTOUKH; JOSETTE DALL' AVA-SANTUCCI; JEAN-CHRISTOPHE MERCIER; GERALD SIMONNEAU; A. TUAN DINH-XUAN

1998-01-01

158

Prenatal programming of pulmonary hypertension induced by chronic hypoxia or ductal ligation in sheep  

PubMed Central

Abstract Pulmonary hypertension of the newborn is caused by a spectrum of functional and structural abnormalities of the cardiopulmonary circuit. The existence of multiple etiologies and an incomplete understanding of the mechanisms of disease progression have hindered the development of effective therapies. Animal models offer a means of gaining a better understanding of the fundamental basis of the disease. To that effect, a number of experimental animal models are being used to generate pulmonary hypertension in the fetus and newborn. In this review, we compare the mechanisms associated with pulmonary hypertension caused by two such models: in utero ligation of the ductus arteriosus and chronic perinatal hypoxia in sheep fetuses and newborns. In this manner, we make direct comparisons between ductal ligation and chronic hypoxia with respect to the associated mechanisms of disease, since multiple studies have been performed with both models in a single species. We present evidence that the mechanisms associated with pulmonary hypertension are dependent on the type of stress to which the fetus is subjected. Such an analysis allows for a more thorough evaluation of the disease etiology, which can help focus clinical treatments. The final part of the review provides a clinical appraisal of current treatment strategies and lays the foundation for developing individualized therapies that depend on the causative factors. PMID:25006393

2013-01-01

159

Diesel Exhaust-Induced Pulmonary and Cardiovascular Impairment: The Role of Hypertension Intervention  

EPA Science Inventory

Background?Exposure to diesel exhaust (DE) particles and associated gases is linked to cardiovascular impairments; however the susceptibility of hypertensive individuals is less well understood. Objective?1) To determine cardiopulmonary effects of gas-phase versus whole-DE, and 2...

160

Sodium-sensitivity and exercise training-induced blood pressure reduction in older hypertensives  

Microsoft Academic Search

Exercise training has been shown to reduce blood pressure in patients with hypertension, but individual responses are variable. Blood pressure responses to sodium loading are also heterogeneous. No studies have determined if sodium-sensitivity status differentially affects the blood pressure response to exercise training. Thus, we sought to determine whether blood pressure reductions with exercise training are different between sodium-sensitive (SS)

Jung-Jun Park; Michael D. Brown; Donald R. Dengel; Mark A. Supiano

2001-01-01

161

Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters  

Microsoft Academic Search

BACKGROUND: Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-?1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette

Tao Wang; Su-Xia Han; Shang-Fu Zhang; Yun-Ye Ning; Lei Chen; Ya-Juan Chen; Guang-Ming He; Dan Xu; Jin An; Ting Yang; Xiao-Hong Zhang; Fu-Qiang Wen

2010-01-01

162

iPLA2? Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling  

PubMed Central

Objectives Calcium independent group VIA phospholipase A2 (iPLA2?) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA2? affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA2? transgenic (iPLA2? -Tg) mice. Method and Results Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA2?-Tg than iPLA2?-Wt mice, whereas, the basal blood pressure was not significantly different. The media thickness and media?lumen ratio of the mesenteric arteries were significantly increased in angiotensin II-infused iPLA2?-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA2? overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced [3H]-leucine incorporation, indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun phosphorylation in vascular smooth muscle cells overexpressing iPLA2? to higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In addition, we found that angiotensin II up-regulated the endogenous iPLA2? protein in-vitro and in-vivo. Conclusion The present study reports that iPLA2? up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways. PMID:22363752

Calderon, Lindsay E.; Liu, Shu; Su, Wen; Xie, Zhongwen; Guo, Zhenheng; Eberhard, Wanda; Gong, Ming C.

2012-01-01

163

Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain  

PubMed Central

Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

2011-01-01

164

Curcumin Induces Nrf2 Nuclear Translocation and Prevents Glomerular Hypertension, Hyperfiltration, Oxidant Stress, and the Decrease in Antioxidant Enzymes in 5/6 Nephrectomized Rats  

PubMed Central

Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8–10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60?mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes. PMID:22919438

Tapia, Edilia; Soto, Virgilia; Ortiz-Vega, Karla Mariana; Zarco-Marquez, Guillermo; Molina-Jijon, Eduardo; Cristobal-Garcia, Magdalena; Santamaria, Jose; Garcia-Nino, Wylly Ramses; Correa, Francisco; Zazueta, Cecilia; Pedraza-Chaverri, Jose

2012-01-01

165

Prevalence of systemic arterial hypertension, electrocardiogram abnormalities, and noise-induced hearing loss in agricultural workers.  

PubMed

ABSTRACT The literature suggests that farmers nowadays are more likely to contract cardiovascular diseases than in the past. This study involved 79 farmers and 64 controls. The workers completed a questionnaire to identify exclusion factors for audiological and cardiovascular risk factors. The participants underwent medical examination, measurement of blood pressure, electrocardiogram, blood tests, audiometry, and measurement of noise exposure. The farmers were found to have a higher prevalence of systolic and diastolic arterial hypertension as well as electrocardiogram (ECG) abnormalities compared with the controls. A significant prevalence of arterial hypertension was detected in the farmers exposed to noise, when compared with those who were not exposed. These results suggest that farmers are at risk of cardiovascular effects and that noise is a cardiovascular risk factor for farmers. PMID:23697692

Tomei, Gianfranco; Sancini, Angela; Tomei, Francesco; Vitarelli, Antonio; Andreozzi, Giorgia; Rinaldi, Giovanni; Di Giorgio, Valeria; Samperi, Ilaria; Fiaschetti, Maria; Tasciotti, Zaira; Cetica, Carlotta; Capozzella, Assunta; Ciarrocca, Manuela; Caciari, Tiziana

2013-01-01

166

Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib  

PubMed Central

SUMMARY Vascular endothelial growth factor inhibitors (VEGFi) are known to cause hypertension and renal injury that severely limits their use as an anticancer therapy. We hypothesized that the angiotensin-converting enzyme inhibitor captopril not only prevents hypertension, but also decreases renal injury caused by the VEGFi sorafenib.Rats were administered sorafenib (20 mg/kg per day) alone or in combination with captopril (40 mg/kg per day) for 4 weeks. Sorafenib administration increased blood pressure, which plateaued by day 10.Concurrent treatment with captopril for 4 weeks resulted in a 30 mmHg decrease in blood pressure compared with sorafenib alone (155 ± 5 vs 182 ± 6 mmHg, respectively; P < 0.05). Furthermore, concurrent captopril treatment reduced albuminuria by 50% compared with sorafenib alone (20 ± 8 vs 42 ± 9 mg/day, respectively; P < 0.05) and reduced nephrinuria by eightfold (280 ± 96 vs 2305 ± 665 ?g/day, respectively; P < 0.05). Glomerular injury, thrombotic micro-angiopathy and tubular cast formation were also decreased in captopril-treated rats administered sorafenib. Renal autoregulatory efficiency was determined by evaluating the afferent arteriolar constrictor response to ATP. Sorafenib administration attenuated the vasoconstriction to ATP, whereas concurrent captopril treatment improved ATP reactivity.In conclusion, captopril attenuated hypertension and renal injury and improved renal autoregulatory capacity in rats administered sorafenib. These findings indicate that captopril treatment, in addition to alleviating the detrimental side-effect of hypertension, decreases the renal injury associated with anticancer VEGFi therapies such as sorafenib. PMID:22443474

Nagasawa, Tasuku; Khan, Abdul Hye; Imig, John D

2013-01-01

167

Propolis reduces oxidative stress in l-NAME-induced hypertension rats.  

PubMed

The inhibition in the synthesis or bioavailability of nitric oxide (NO) has an important role in progress of hypertension. The blocking of nitric oxide synthase activity may cause vasoconstriction with the formation of reactive oxygen species (ROS). Propolis is a resinous substance collected by honey bees from various plants. Propolis has biological and pharmacological properties. The aim of this study was to examine the effect of propolis on catalase (CAT) activity, malondialdehyde (MDA) and NO levels in the testis tissues of hypertensive rats by N?-nitro-l-arginine methyl ester (l-NAME). Rats have received nitric oxide synthase inhibitor (l-NAME, 40 mg kg(-1) , intraperitoneally) for 15 days to produce hypertension and propolis (200 mg kg(-1) , by gavage) during the last 5 days. MDA level in l-NAME-treated group significantly increased compared with control group (P < 0.01). MDA level of l-NAME + propolis-treated rats significantly reduced (P < 0.01) compared with l-NAME-treated group. CAT activity and NO level significantly reduced (P < 0.01) in l-NAME group compared with control group. There were no statistically significant increases in the CAT activity and NO level of the l-NAME + propolis group compared with the l-NAME-treated group (P > 0.01). These results suggest that propolis changes CAT activity, NO and MDA levels in testis of l-NAME-treated animals, and so it may modulate the antioxidant system. PMID:23788129

Selamoglu Talas, Zeliha

2014-03-01

168

Increased nitric oxide bioavailability in adult GRK2 hemizygous mice protects against angiotensin II-induced hypertension.  

PubMed

G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous serine/threonine protein kinase able to phosphorylate and desensitize the active form of several G protein-coupled receptors. Given the lack of selective inhibitors for GRK2, we investigated the effects elicited by GRK2 inhibition in vascular responses using global adult hemizygous mice (GRK2(+/-)). The vasodilator responses to acetylcholine or isoproterenol were increased in aortas and mesenteric resistance arteries from GRK2(+/-) mice compared with wild-type (WT) littermates. After angiotensin II (AngII) infusion, GRK2(+/-) mice were partially protected against hypertension, vascular remodeling, and mechanical alterations, even when resting basal blood pressures were not significantly different. AngII infusion also (1) increased GRK2 levels in WT but not in GRK2(+/-) vessels; (2) increased vasoconstrictor responses to phenylephrine in WT but not in GRK2(+/-) mice; and (3) decreased vasodilator responses to acetylcholine and vascular pAkt and eNOS levels more in WT than in GRK2(+/-) animals. Vascular NO production and the modulation of vasoconstrictor responses by endothelial-derived NO remained enhanced in GRK2(+/-) mice infused with AngII. Thus, GRK2(+/-) mice are resistant to the development of vascular remodeling and mechanical alterations, endothelial dysfunction, increased vasoconstrictor responses, and hypertension induced by AngII at least partially through the preservation of NO bioavailability. In conclusion, our results describe an important role for GRK2 in systemic hypertension and further establish that an inhibition of GRK2 could be a beneficial treatment for this condition. PMID:24191280

Avendaño, María S; Lucas, Elisa; Jurado-Pueyo, María; Martínez-Revelles, Sonia; Vila-Bedmar, Rocío; Mayor, Federico; Salaices, Mercedes; Briones, Ana M; Murga, Cristina

2014-02-01

169

Protective effects of 10-nitro-oleic acid in a hypoxia-induced murine model of pulmonary hypertension.  

PubMed

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment. The infiltration of macrophages and the generation of reactive oxygen species were elevated in lung tissue of mice on hypoxia and were diminished by OA-NO2 treatment. Moreover, OA-NO2 decreased superoxide production of activated macrophages and PASMCs in vitro. Vascular structural remodeling was also limited by OA-NO2. In support of these findings, proliferation and activation of extracellular signal-regulated kinases 1/2 in cultured PASMCs was less pronounced on application of OA-NO2.Our results show that the oleic acid nitroalkene derivative OA-NO2 attenuates hypoxia-induced pulmonary hypertension in mice. Thus, OA-NO2 represents a potential therapeutic agent for the treatment of PAH. PMID:24521348

Klinke, Anna; Möller, Annika; Pekarova, Michaela; Ravekes, Thorben; Friedrichs, Kai; Berlin, Matthias; Scheu, Katrin M; Kubala, Lukas; Kolarova, Hana; Ambrozova, Gabriela; Schermuly, Ralph T; Woodcock, Steven R; Freeman, Bruce A; Rosenkranz, Stephan; Baldus, Stephan; Rudolph, Volker; Rudolph, Tanja K

2014-07-01

170

Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.  

PubMed

The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASCCOX-1) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASCCOX-1 or untransduced ASCs. The intratracheal administration of ASCCOX-1 3 × 10(6) cells on day 14 after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured on day 35 after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASCCOX-1 persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASCCOX-1 in the lung. These data emphasize the effectiveness of ASCCOX-1 in the treatment of experimentally induced PH. PMID:25320332

Somanna, Naveen K; Wörner, Philipp M; Murthy, Subramanyam N; Pankey, Edward A; Schächtele, Deborah J; St Hilaire, Rose-Claire; Jansen, David; Chaffin, Abigail E; Nossaman, Bobby D; Alt, Eckhard U; Kadowitz, Philip J; Izadpanah, Reza

2014-10-15

171

Angiotensin II-induced hypertension increases plasma membrane Na pump activity by enhancing Na entry in rat thick ascending limbs.  

PubMed

Thick ascending limbs (TAL) reabsorb 30% of the filtered NaCl load. Na enters the cells via apical Na-K-2Cl cotransporters and Na/H exchangers and exits via basolateral Na pumps. Chronic angiotensin II (ANG II) infusion increases net TAL Na transport and Na apical entry; however, little is known about its effects on the basolateral Na pump. We hypothesized that in rat TALs Na pump activity is enhanced by ANG II-infusion, a model of ANG II-induced hypertension. Rats were infused with 200 ng·kg(-1)·min(-1) ANG II or vehicle for 7 days, and TAL suspensions were obtained. We studied plasma membrane Na pump activity by measuring changes in 1) intracellular Na (Nai) induced by ouabain; and 2) ouabain-sensitive oxygen consumption (QO2). We found that the ouabain-sensitive rise in Nai in TALs from ANG II-infused rats was 12.8 ± 0.4 arbitrary fluorescent units (AFU)·mg(-1)·min(-1) compared with only 9.9 ± 1.1 AFU·mg(-1)·min(-1) in controls (P < 0.024). Ouabain-sensitive oxygen consumption was 17 ± 5% (P < 0.043) greater in tubules from ANG II-treated than vehicle rats. ANG II infusion did not alter total Na pump expression, the number of Na pumps in the plasma membrane, or the affinity for Na. When furosemide (1.1 mg·kg(-1)·day(-1)) was coinfused with ANG II, no increase in plasma membrane Na pump activity was observed. We concluded that in ANG II-induced hypertension Na pump activity is increased in the plasma membrane of TALs and that this increase is caused by the chronically enhanced Na entry occurring in this model. PMID:23986517

Gonzalez-Vicente, Agustin; Garvin, Jeffrey L

2013-11-01

172

INCREASED ANGIOTENSIN II INDUCED HYPERTENSION AND INFLAMMATORY CYTOKINES IN MICE LACKING ANGIOTENSIN CONVERTING ENZYME N DOMAIN ACTIVITY  

PubMed Central

Angiotensin converting enzyme (ACE) is composed of the N- and C-terminal catalytic domains. To study the role of the ACE domains in the inflammatory response, N-KO and C-KO mice, models lacking one of the two ACE domains, were analyzed during angiotensin II-induced hypertension. At 2 weeks, N-KO mice have systolic blood pressures that averaged 173 ± 4.6 mm Hg, which is more than 25 mm Hg higher than the blood pressures observed in wild-type or C-KO mice (146 ± 3.2 and 147 ± 4.2 mm Hg). After 3 weeks, blood pressure differences between N-KO, C-KO and WT were even more pronounced. Macrophages from N-KO mice have increased expression of tumor necrosis factor ? after stimulation with either lipopolysaccharide (about 4-fold) or angiotensin II (about 2-fold), as compared to C-KO or wild-type mice. Inhibition of the enzyme prolyl oligopeptidase, responsible for the formation of acetyl SDKP and other peptides, eliminated the blood pressure difference and the difference in tumor necrosis factor ? expression between angiotensin II treated N-KO and wild-type mice. However, this appears independent of acetyl SDKP. These data establish significant differences in the inflammatory response as a function of ACE N- or C-domain catalytic activity. They also indicate a novel role of prolyl oligopeptidase in the cytokine regulation and in the blood pressure response to experimental hypertension. PMID:22203735

Ong, Frank S.; Lin, Chentao X.; Campbell, Duncan J.; Okwan-Duodu, Derick; Chen, Xu; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien; Bernstein, Kenneth E.

2012-01-01

173

Amlodipine induces a flow and pressure-independent vasoactive effect on the brachial artery in hypertension.  

PubMed Central

1. The objectives of this study were to study the flow-dependent arterial reactivity and pressure-independent arterial compliance of the calcium antagonist amlodipine in hypertensive men. 2. Twenty-one hypertensive patients were randomized to receive 2 months treatment with placebo (n = 10) or 5-10 mg amlodipine (n = 11) once a day. Non-invasive measurement of brachial artery mean blood pressure, diameter and flow (pulsed Doppler) and compliance (arterial mechanography and logarithmic elastic model) were obtained before and after drug administration. Vasoreactivity was studied by means of response of the brachial artery during exclusion of the hand and hyperaemia post-ischaemia. 3. Compared with placebo, amlodipine reduced mean blood pressure (% change +/- s.e. mean 11 +/- 1% vs 4 +/- 3%, P < 0.05), and increased arterial compliance at prevailing pressure (44 +/- 13%, vs 1 +/- 8%, P < 0.05) and at isobaric pressure (26 +/- 10% vs -3 +/- 6%, P < 0.05). A significant % change increase from baseline in brachial artery diameter between placebo and amlodipine was observed at rest (-2 +/- 3 vs 8 +/- 3%; P < 0.05), after wrist occlusion (-3 +/- 3 vs 6 +/- 2%; P < 0.05) and during reactive hyperaemia (-5 +/- 3 vs 18 +/- 5%; P < 0.05). No significant differences between amlodipine and placebo groups were observed in blood velocity after forearm manoeuvres before and after treatment. 4. No differences were observed between groups in brachial flow-dependent vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7654482

Megnien, J L; Levenson, J; Del-Pino, M; Simon, A

1995-01-01

174

Naringenin adds to the protective effect of L-arginine in monocrotaline-induced pulmonary hypertension in rats: favorable modulation of oxidative stress, inflammation and nitric oxide.  

PubMed

The present study was directed to investigate the possible modulatory effect of naringenin when co-administered with L-arginine in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). L-arginine (500 mg/kg) and naringenin (50 mg/kg) were orally administered daily, alone and in combination, for 3 weeks. Mean arterial blood pressure, electrocardiography and echocardiography were then recorded and rats were sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Combined therapy provided a significant improvement in L-arginine protective effect toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline treatment. Furthermore, combined therapy prevented monocrotaline-induced changes in endothelial and inducible nitric oxide synthase protein expression as well as histological analysis compared with either treatment alone. In conclusion, naringenin significantly adds to the protective effect of L-arginine in pulmonary hypertension induced by monocrotaline in rats. PMID:24878387

Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M

2014-10-01

175

CTGF disrupts alveolarization and induces pulmonary hypertension in neonatal mice: implication in the pathogenesis of severe bronchopulmonary dysplasia  

PubMed Central

The pathological hallmarks of bronchopulmonary dysplasia (BPD), one of the most common long-term pulmonary complications associated with preterm birth, include arrested alveolarization, abnormal vascular growth, and variable interstitial fibrosis. Severe BPD is often complicated by pulmonary hypertension characterized by excessive pulmonary vascular remodeling and right ventricular hypertrophy that significantly contributes to the mortality and morbidity of these infants. Connective tissue growth factor (CTGF) is a multifunctional protein that coordinates complex biological processes during tissue development and remodeling. We have previously shown that conditional overexpression of CTGF in airway epithelium under the control of the Clara cell secretory protein promoter results in BPD-like architecture in neonatal mice. In this study, we have generated a doxycycline-inducible double transgenic mouse model with overexpression of CTGF in alveolar type II epithelial (AT II) cells under the control of the surfactant protein C promoter. Overexpression of CTGF in neonatal mice caused dramatic macrophage and neutrophil infiltration in alveolar air spaces and perivascular regions. Overexpression of CTGF also significantly decreased alveolarization and vascular development. Furthermore, overexpression of CTGF induced pulmonary vascular remodeling and pulmonary hypertension. Most importantly, we have also demonstrated that these pathological changes are associated with activation of integrin-linked kinase (ILK)/glucose synthesis kinase-3? (GSK-3?)/?-catenin signaling. These data indicate that overexpression of CTGF in AT II cells results in lung pathology similar to those observed in infants with severe BPD and that ILK/GSK-3?/?-catenin signaling may play an important role in the pathogenesis of severe BPD. PMID:21239535

Chen, Shaoyi; Rong, Min; Platteau, Astrid; Hehre, Dorothy; Smith, Heather; Ruiz, Philip; Whitsett, Jeffrey; Bancalari, Eduardo

2011-01-01

176

Protein complex formation with heat shock protein 90 in chronic hypoxia-induced pulmonary hypertension in newborn piglets.  

PubMed

Aberrant interactions between heat shock protein (Hsp)90 and its client proteins could contribute to pulmonary hypertension. We tested the hypotheses that 1) the interaction between Hsp90 and its known client protein, endothelial nitric oxide synthase (eNOS), is impaired in pulmonary resistance arteries (PRAs) from piglets with pulmonary hypertension caused by exposure to 3 or 10 days of hypoxia and 2) Hsp90 interacts with the prostanoid pathway proteins prostacyclin synthase (PGIS) and/or thromboxane synthase (TXAS). We also determined whether Hsp90 antagonism with geldanamycin alters the agonist-induced synthesis of prostacyclin and thromboxane or alters PRA responses to these prostaglandin metabolites. Compared with normoxic piglets, less eNOS coimmunoprecipitated with Hsp90 in PRAs from hypoxic piglets. Despite reduced Hsp90-eNOS interactions, dilation to ACh was enhanced in geldanamycin-treated PRAs from hypoxic, but not normoxic, piglets. In PRAs from all groups of piglets, PGIS and TXAS coimmunoprecipitated with Hsp90. Geldanamycin reduced the ACh-induced synthesis of prostacyclin and thromboxane and altered responses to the thromboxane mimetic U-46619 in PRAs from all groups. Although geldanamycin enhanced responses to prostacyclin in PRAs from both groups of hypoxic piglets, geldanamycin had no effect on prostacyclin responses in PRAs from either group of normoxic piglets. Our findings indicate that Hsp90 influences both prostanoid and eNOS signaling in the pulmonary circulation of newborn piglets and that the impact of pharmacological inhibition of Hsp90 on these signaling pathways is altered during exposure to chronic hypoxia. PMID:20693398

Fike, Candice D; Pfister, Sandra L; Slaughter, James C; Kaplowitz, Mark R; Zhang, Yongmei; Zeng, Heng; Frye, Naila Rashida; Aschner, Judy L

2010-10-01

177

Pharmacological inhibition of inducible nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, convalesce behavior and biochemistry of hypertension induced vascular dementia in rats.  

PubMed

Cognitive disorders are likely to increase over the coming years (5-10). Vascular dementia (VaD) has heterogeneous pathology and is a challenge for clinicians. Current Alzheimer's disease drugs have had limited clinical efficacy in treating VaD and none have been approved by major regulatory authorities specifically for this disease. Role of iNOS and NADPH-oxidase has been reported in various pathological conditions but there role in hypertension (Hypt) induced VaD is still unclear. This research work investigates the salutiferous effect of aminoguanidine (AG), an iNOS inhibitor and 4'-hydroxy-3'-methoxyacetophenone (HMAP), a NADPH oxidase inhibitor in Hypt induced VaD in rats. Deoxycorticosterone acetate-salt (DOCA-S) hypertension has been used for development of VaD in rats. Morris water-maze was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Mean arterial blood pressure (MABP), oxidative stress [aortic superoxide anion, serum and brain thiobarbituric acid reactive species (TBARS) and brain glutathione (GSH)], nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity-AChE) were also measured. DOCA-S treated rats have shown increased MABP with impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate & brain GSH levels along with increase in serum & brain TBARS, and brain AChE activity. AG as well as HMAP significantly convalesce Hypt induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that AG, an iNOS inhibitor and HMAP, a NADPH-oxidase inhibitor may be considered as potential agents for the management of Hypt induced VaD. PMID:23201648

Sharma, Bhupesh; Singh, Nirmal

2013-02-01

178

Effects of angiotensin 1-7 on the actions of angiotensin II in the renal and mesenteric vasculature of hypertensive and streptozotocin-induced diabetic rats  

Microsoft Academic Search

Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin–angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent

Murugan Dharmani; Mohd. Rais Mustafa; Francis I. Achike; Meng-Kwoon Sim

2007-01-01

179

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2  

Microsoft Academic Search

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin–angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH

Su-Xia Han; Guang-Ming He; Tao Wang; Lei Chen; Yun-Ye Ning; Feng Luo; Jin An; Ting Yang; Jia-Jia Dong; Zeng-lin Liao; Dan Xu; Fu-Qiang Wen

2010-01-01

180

Disulfiram-Induced Reversible Hypertension: A Prospective Case Series and Review of The Literature  

PubMed Central

Disulfiram (DSF) is one of the recommended aids in the management of selected patients with alcohol dependence. Hypertension (HTN) as an adverse effect of DSF therapy is less understood. In our prospective case series of 7 subjects with co-morbid alcohol and nicotine dependence, a temporal, dose-dependent, and reversible grade 1-3 HTN within 1-6 weeks of initiation of DSF therapy (125-500 mg/day) with no other detectable causes of HTN was noted. Challenges and strategies surrounding diagnosis and treatment along with mean change and percentage rise in blood pressure are described. Literature review and clinical description of case series may suggest neurobiological role in its causation. HTN may be a clinically significant, dose-dependent, and reversible adverse effect of DSF therapy, especially in co-morbid alcohol and nicotine-dependent patients. Awareness amongst clinicians may render better health care delivery to subjects with alcohol dependence. PMID:25336781

Kulkarni, Ranganath R.; Ramdurg, Santosh I.; Bairy, Bhavya K.

2014-01-01

181

Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension.  

PubMed

The physiological and pathophysiological significance of collecting duct (CD)-derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP and renal salt and water excretion. Mice containing loxP-flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin-2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal-Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400 ng·kg(-1)·min(-1) resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 ± 4 mmHg in KO vs. 128 ± 3 mmHg in controls). Urinary renin excretion and epithelial Na(+) channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane-associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression. PMID:25122048

Ramkumar, Nirupama; Stuart, Deborah; Rees, Sara; Hoek, Alfred Van; Sigmund, Curt D; Kohan, Donald E

2014-10-15

182

Role of blood cell-associated angiotensin II type 1 receptors in the cerebral microvascular response to ischemic stroke during angiotensin-induced hypertension  

PubMed Central

Background Angiotensin II type 1 receptor (AT1R) blockers lower the incidence of ischemic stroke in hypertensive patients and attenuate brain inflammation and injury in animal models. Although AT1R on both blood cells (BC) and vascular endothelial cells (EC) can be activated by angiotensin II (Ang II) to elicit inflammation, little is known about the relative contributions of AT1R expressed on BC and EC to the brain injury responses to ischemia and reperfusion (I/R) in the setting of angiotensin-induced hypertension. Methods The contributions of BC- and EC-associated AT1R to I/R-induced brain inflammation and injury were evaluated using wild type (WT), AT1aR-/-, and bone marrow chimera mice with either a BC+/EC+ (WT?WT) or BC-/EC+ (AT1aR-/-?WT) distribution of AT1aR. The adhesion of leukocytes and platelets in venules, blood brain barrier (BBB) permeability and infarct volume were monitored in postischemic brain of normotensive and Ang II-induced hypertensive mice. Results The inflammatory (blood cell adhesion) and injury (BBB permeability, infarct volume) responses were greatly exaggerated in the presence of Ang II-induced hypertension. The Ang II-enhanced responses were significantly blunted in AT1aR-/- mice. A similar level of protection was noted in AT1aR-/- ?WT mice for BBB permeability and infarct volume, while less or no protection was evident for leukocyte and platelet adhesion, respectively. Conclusions BC- and EC-associated AT1aR are both involved in the brain injury responses to ischemic stroke during Ang II-hypertension, with EC AT1aR contributing more to the blood cell recruitment response and BC AT1aR exerting a significant influence on the BBB disruption and tissue necrosis elicited by I/R. PMID:22087550

2011-01-01

183

AAV Delivery of Tumor Necrosis Factor-? Short Hairpin RNA Attenuates Cold-Induced Pulmonary Hypertension and Pulmonary Arterial Remodeling.  

PubMed

Cold temperatures are associated with increased mortality and morbidity of cardiovascular and pulmonary disease. Cold exposure causes lung inflammation, pulmonary hypertension (PH), and right ventricle hypertrophy, but there is no effective therapy because of unknown mechanism. Here, we investigated whether RNA interference silencing of tumor necrosis factor (TNF)-? decreases cold-induced macrophage infiltration, PH, and pulmonary arterial (PA) remodeling. We found for the first time that continuous cold exposure (5.0°C) increased TNF-? expression and macrophage infiltration in the lungs and PAs right before elevation of right ventricle systolic pressure. The in vivo RNA interference silencing of TNF-? was achieved by intravenous delivery of recombinant AAV-2 carrying TNF-? short hairpin small-interfering RNA 24 hours before cold exposure. Cold exposure for 8 weeks significantly increased right ventricle pressure compared with the warm controls (40.19±4.9 versus 22.9±1.1 mm Hg), indicating that cold exposure caused PH. Cold exposure increased TNF-?, interleukin-6, and phosphodiesterase-1C protein expression in the lungs and PAs and increased lung macrophage infiltration. Notably, TNF-? short hairpin small-interfering RNA prevented the cold-induced increases in TNF-?, interleukin-6, and phosphodiesterase-1C protein expression, abolished lung macrophage infiltration, and attenuated PH (26.28±1.6 mm Hg), PA remodeling, and right ventricle hypertrophy. PA smooth muscle cells isolated from cold-exposed animals showed increased intracellular superoxide levels and cell proliferation along with decreased intracellular cGMP. These cold-induced changes were prevented by TNF-? short hairpin small-interfering RNA. In conclusions, upregulation of TNF-? played a critical role in the pathogenesis of cold-induced PH by promoting pulmonary macrophage infiltration and inflammation. AAV delivery of TNF-? short hairpin small-interfering RNA may be an effective therapeutic approach for cold-induced PH and PA remodeling. PMID:25185133

Crosswhite, Patrick; Chen, Kai; Sun, Zhongjie

2014-11-01

184

Eosinophils are necessary for pulmonary arterial remodeling in a mouse model of eosinophilic inflammation-induced pulmonary hypertension.  

PubMed

There is increasing evidence that inflammation plays a pivotal role in the pathogenesis of some forms of pulmonary hypertension (PH). We recently demonstrated that deficiency of adiponectin (APN) in a mouse model of PH induced by eosinophilic inflammation increases pulmonary arterial remodeling, pulmonary pressures, and the accumulation of eosinophils in the lung. Based on these data, we hypothesized that APN deficiency exacerbates PH indirectly by increasing eosinophil recruitment. Herein, we examined the role of eosinophils in the development of inflammation-induced PH. Elimination of eosinophils in APN-deficient mice by treatment with anti-interleukin-5 antibody attenuated pulmonary arterial muscularization and PH. In addition, we observed that transgenic mice that are devoid of eosinophils also do not develop pulmonary arterial muscularization in eosinophilic inflammation-induced PH. To investigate the mechanism by which APN deficiency increased eosinophil accumulation in response to an allergic inflammatory stimulus, we measured expression levels of the eosinophil-specific chemokines in alveolar macrophages isolated from the lungs of mice with eosinophilic inflammation-induced PH. In these experiments, the levels of CCL11 and CCL24 were higher in macrophages isolated from APN-deficient mice than in macrophages from wild-type mice. Finally, we demonstrate that the extracts of eosinophil granules promoted the proliferation of pulmonary arterial smooth muscle cells in vitro. These data suggest that APN deficiency may exacerbate PH, in part, by increasing eosinophil recruitment into the lung and that eosinophils could play an important role in the pathogenesis of inflammation-induced PH. These results may have implications for the pathogenesis and treatment of PH caused by vascular inflammation. PMID:21908591

Weng, M; Baron, D M; Bloch, K D; Luster, A D; Lee, J J; Medoff, B D

2011-12-01

185

TRPV4 channel contributes to serotonin-induced pulmonary vasoconstriction and the enhanced vascular reactivity in chronic hypoxic pulmonary hypertension  

PubMed Central

Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive channel in pulmonary arterial smooth muscle cells (PASMCs). Its upregulation by chronic hypoxia is associated with enhanced myogenic tone, and genetic deletion of trpv4 suppresses the development of chronic hypoxic pulmonary hypertension (CHPH). Here we further examine the roles of TRPV4 in agonist-induced pulmonary vasoconstriction and in the enhanced vasoreactivity in CHPH. Initial evaluation of TRPV4-selective antagonists HC-067047 and RN-1734 in KCl-contracted pulmonary arteries (PAs) of trpv4?/? mice found that submicromolar HC-067047 was devoid of off-target effect on pulmonary vasoconstriction. Inhibition of TRPV4 with 0.5 ?M HC-067047 significantly reduced the sensitivity of serotonin (5-HT)-induced contraction in wild-type (WT) PAs but had no effect on endothelin-1 or phenylephrine-activated response. Similar shift in the concentration-response curve of 5-HT was observed in trpv4?/? PAs, confirming specific TRPV4 contribution to 5-HT-induced vasoconstriction. 5-HT-induced Ca2+ response was attenuated by HC-067047 in WT PASMCs but not in trpv4?/? PASMCs, suggesting TRPV4 is a major Ca2+ pathway for 5-HT-induced Ca2+ mobilization. Nifedipine also attenuated 5-HT-induced Ca2+ response in WT PASMCs but did not cause further reduction in the presence of HC-067047, suggesting interdependence of TRPV4 and voltage-gated Ca2+ channels in the 5-HT response. Chronic exposure (3–4 wk) of WT mice to 10% O2 caused significant increase in 5-HT-induced maximal contraction, which was partially reversed by HC-067047. In concordance, the enhancement of 5-HT-induced contraction was significantly reduced in PAs of CH trpv4?/? mice and HC-067047 had no further effect on the 5-HT induced response. These results suggest unequivocally that TRPV4 contributes to 5-HT-dependent pharmaco-mechanical coupling and plays a major role in the enhanced pulmonary vasoreactivity to 5-HT in CHPH. PMID:23739180

Xia, Yang; Fu, Zhenzhen; Hu, Jinxing; Huang, Chun; Paudel, Omkar; Cai, Shaoxi; Liedtke, Wolfgang

2013-01-01

186

Effect of Small Hairpin RNA Targeting Endothelin-Converting Enzyme-1 in Monocrotaline-Induced Pulmonary Hypertensive Rats  

PubMed Central

The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ETA) were significantly decreased in the shRNA group in week 4. The protein levels of ETA were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-? and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension. PMID:23255850

Son, Jae Sung; Kim, Kwan Chang; Kim, Bo Kyung; Cho, Min-Sun

2012-01-01

187

Asymmetrical changes in blood–brain barrier permeability during pentylenetetrazol-induced seizures and in acute hypertension  

Microsoft Academic Search

The asymmetrical breakdown of the blood–brain barrier to Evans-blue was studied in male and female rats during epileptiform seizures and in acute hypertension. The animals were divided into six groups. Group I: control female; Group II: control male; Group III: female+acute hypertension; Group IV: male+acute hypertension; Group V: female+seizure; Group VI: male+seizure. Asymmetric breakdown of the blood–brain barrier had been

Baria Özta?

1998-01-01

188

Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis  

PubMed Central

Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. ?-Galactosidase staining in PRCPgt/gt mice reveals expression in kidney and vasculature. Invasive telemetric monitorings show that PRCPgt/gt mice have significantly elevated blood pressure. PRCPgt/gt mice demonstrate shorter carotid artery occlusion times in 2 models, and their plasmas have increased thrombin generation times. Pharmacologic inhibition of PRCP with Z-Pro-Prolinal or plasma kallikrein with soybean trypsin inhibitor, Pro-Phe-Arg-chloromethylketone or PKSI 527 also shortens carotid artery occlusion times. Aortic and renal tissues have uncoupled eNOS and increased reactive oxygen species (ROS) in PRCPgt/gt mice as detected by dihydroethidium or Amplex Red fluorescence or lucigenin luminescence. The importance of ROS is evidenced by the fact that treatment of PRCPgt/gt mice with antioxidants (mitoTEMPO, apocynin, Tempol) abrogates the hypertensive, prothrombotic phenotype. Mechanistically, our studies reveal that PRCPgt/gt aortas express reduced levels of Kruppel-like factors 2 and 4, thrombomodulin, and eNOS mRNA, suggesting endothelial cell dysfunction. Further, PRCP siRNA treatment of endothelial cells shows increased ROS and uncoupled eNOS and decreased protein C activation because of thrombomodulin inactivation. Collectively, our studies identify PRCP as a novel regulator of vascular ROS and homeostasis. PMID:21297000

Adams, Gregory N.; LaRusch, Gretchen A.; Stavrou, Evi; Zhou, Yihua; Nieman, Marvin T.; Jacobs, Gretta H.; Cui, Yingjie; Lu, Yuan; Jain, Mukesh K.; Mahdi, Fakhri; Shariat-Madar, Zia; Okada, Yoshio; D'Alecy, Louis G.

2011-01-01

189

Alterations of N-3 Polyunsaturated Fatty Acid-Activated K2P Channels in Hypoxia-Induced Pulmonary Hypertension  

PubMed Central

Polyunsaturated fatty acid (PUFA)-activated two-pore domain potassium channels (K2P) have been proposed to be expressed in the pulmonary vasculature. However, their physiological or pathophysiological roles are poorly defined. Here we tested the hypothesis that PUFA-activated K2P are involved in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch clamp (PC), and myography. K2P-gene expression was examined in chronic hypoxic mice. QRT-PCR showed that the K2P2.1 and K2P6.1 were the predominantly expressed K2P in the murine lung. IHC revealed protein expression of K2P2.1 and K2P6.1 in the endothelium of pulmonary arteries and of K2P6.1 in bronchial epithelium. PC showed pimozide-sensitive K2P-like K+-current activated by docosahexaenoic acid (DHA) in freshly isolated endothelial cells as well as DHA-induced membrane hyperpolarization. Myography on pulmonary arteries showed that DHA-induced concentration-dependent and instantaneous relaxations that were resistant to endothelial removal and inhibition of NO and prostacyclin synthesis and to a cocktail of blockers of calcium-activated K+ channels but were abolished by high extracellular (30 mM) K+-concentration. Gene expression and protein of K2P2.1 were not altered in chronic hypoxic mice while K2P6.1 was up-regulated by fourfold. In conclusion, the PUFA-activated K2P2.1 and K2P6.1 are expressed in murine lung and functional K2P-like channels contribute to endothelium-hyperpolarization and pulmonary artery relaxation. The increased K2P6.1-gene expression may represent a novel counter-regulatory mechanism in pulmonary hypertension, and suggest that arterial K2P2.1 and K2P6.1 could be novel therapeutic targets. PMID:23724868

Nielsen, Gorm; Wandall-Frostholm, Christine; Sadda, Veeranjaneyulu; Olivan-Viguera, Aida; Lloyd, Eric E.; Bryan, Robert M.; Simonsen, Ulf; Kohler, Ralf

2013-01-01

190

Angiotensin II-induced hypertension in the rat. Effects on the plasma concentration, renal excretion, and tissue release of prostaglandins.  

PubMed Central

We examined in rats the effects of intraperitoneal angiotensin II (AII) infusion for 12 d on urinary excretion, plasma concentration, and in vitro release of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a PGI2 metabolite. AII at 200 ng/min increased systolic blood pressure (SBP) progressively from 125 +/- 3 to 170 +/- 9 mmHg (P less than 0.01) and elevated fluid intake and urine volume. Urinary 6-keto-PGF1 alpha excretion increased from 38 +/- 6 to 55 +/- 5 and 51 +/- 7 ng/d (P less than 0.05) on days 8 and 11, respectively, of AII infusion, but urinary PGE2 excretion did not change. Relative to a control value of 129 +/- 12 pg/ml in vehicle-infused (V) rats, arterial plasma 6-keto-PGF1 alpha concentration increased by 133% (P less than 0.01) with AII infusion. Aortic rings from AII-infused rats released more 6-keto-PGF1 alpha (68 +/- 7 ng/mg) during 15-min incubation in Krebs solution than did rings from V rats (40 +/- 3 ng/mg); release of PGE2, which was less than 1% of that of 6-keto-PGF1 alpha, was also increased. Slices of inner renal medulla from AII-infused rats released more 6-keto-PGF1 alpha (14 +/- 1 ng/mg) during incubation than did slices from V rats (8 +/- 1 ng/mg, P less than 0.05), but PGE2 release was not altered. In contrast, AII infusion did not alter release of 6-keto-PGF1 alpha or PGE2 from inferior vena cava segments or from renal cortex slices. Infusion of AII at 125 ng/min also increased SBP, plasma 6-keto-PGF1 alpha concentration, and in vitro release of 6-keto-PGF1 alpha from rings of aorta and renal inner medulla slices; at 75 ng/min AII had no effect. SBP on AII infusion day 11 correlated positively with both 6-keto-PGF1 alpha plasma concentration (r = 0.54) and net aortic ring release (r = 0.70) when data from all rats were combined. We conclude that augmentation of PGI2 production is a feature of AII-induced hypertension. The enhancement of PGI2 production may be an expression of nonspecific alteration in vascular structure and metabolic functions during AII-induced hypertension, as well as the result of a specific effect of the peptide on the arachidonate-prostaglandin system. PMID:6575977

Diz, D I; Baer, P G; Nasjletti, A

1983-01-01

191

Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation.  

PubMed

Since inhibition of angiotensin II type 1 (AT1) receptor reduces chronic inflammation associated with hypertension, we evaluated the anti-inflammatory potential and the underlying mechanism of fimasartan, a Korean Food and Drug Administration approved anti-hypertension drug, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Fimasartan suppressed the expressions of inducible nitric oxide synthase (iNOS) by down-regulating its transcription, and subsequently inhibited the productions of nitric oxide (NO). In addition, fimasartan attenuated LPS-induced transcriptional and DNA-binding activities of nuclear factor-kappa B (NF-?B) and activator protein-1 (AP-1). These reductions were accompanied by parallel reductions in the nuclear translocation of NF-?B and AP-1. Taken together, our data suggest that fimasartan down-regulates the expression of the iNOS in macrophages via NF-?B and AP-1 inactivation. PMID:23449332

Ryu, Suran; Shin, Ji-Sun; Cho, Young-Wuk; Kim, Hyoung Kook; Paik, Soo Heui; Lee, Joo Han; Chi, Yong Ha; Kim, Ji Han; Kim, Je Hak; Lee, Kyung-Tae

2013-01-01

192

Gender differences in hypothalamic tyrosine hydroxylase and alpha(2)-adrenoceptor subtype gene expression in cafeteria diet-induced hypertension and consequences of neonatal androgenization.  

PubMed

This study investigated the incidence of cafeteria-diet induced hypertension on hypothalamic tyrosine hydroxylase (TH) and alpha(2)-adrenoceptor subtype gene expression in male, female, and neonatally testosterone-imprinted female rats. After 10 weeks of cafeteria diet, all these rats were hyperleptinemic. In contrast, males and testosterone-treated females developed hypertension, whereas intact females remained normotensive. In these rats, cafeteria diet up-regulated TH gene expression only in males and testosterone-treated females. On the other hand, cafeteria diet differentially affected hypothalamic gene expression of alpha(2)-adrenoceptor subtypes. In fact, this diet increased alpha(2A)-adrenoceptor mRNA levels only in intact normotensive females. In contrast, gene expression of the alpha(2B)-adrenoceptor was up-regulated only in male and testosterone-treated female cafeteria-fed rats. Furthermore, an alpha(2C)-adrenoceptor gene over-expression was also induced, but only in male cafeteria-fed rats. If one assumes that the up-regulations in TH and alpha(2B)-adrenoceptor gene expression are indicative of increased sympathetic nervous activity, then, these altered gene expressions could be responsible for the maintenance of high blood pressure in male and testosterone-treated female cafeteria-fed rats. Conversely, in intact females, the absence of these over-expressions and the up-regulation of the alpha(2A)-adrenoceptor gene expression could reflect an adaptive response to the diet and, consequently, could be protective against cafeteria diet-induced hypertension. Moreover, neonatal testosterone imprinting in females could have induced an irreversible android susceptibility to the cafeteria diet, leading to the onset of hypertension. PMID:12130711

Plut, Charles; Ribiere, Catherine; Giudicelli, Yves; Dausse, Jean-Pierre

2002-08-01

193

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy  

NASA Technical Reports Server (NTRS)

BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)

2000-01-01

194

SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO AIRWAY DISEASE INDUCED BY SULFUR DIOXIDE  

EPA Science Inventory

Rodent models of chronic pulmonary diseases induced by sulfur dioxide (SO2), elastase or tobacco smoke have limited utility because of their lack of chronicity of inflammation, and they demonstrate limited sensitivity to a given experimental manipulation. We hypothesized that dis...

195

Hypoxia-induced pulmonary hypertension in an optimized environment for the guineapig  

Microsoft Academic Search

Summary Prolonged exposure to hypoxia elicits a variety of time-related morphologic and physiologic changes in the pulmonary vasculature of mammals, including humans. The study of hypoxia- induced changes in rodents generally requires a prolonged exposure to 9% oxygen for a minimum of 10 days in an airtight chamber, which has only been generally described in the literature as large (200-4001),

Steven Bochnowicz; Ruth R. Osborn; W. P. Hay; David C. Underwood

1997-01-01

196

Glomerular Filtration Rate Measured by 51Cr-EDTA Clearance: Evaluation of Captopril-Induced Changes in Hypertensive Patients with and without Renal Artery Stenosis  

PubMed Central

INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis (51Cr-EDTA) and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m2 in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m2 in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/ kg/1.73m2, p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m2, p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show significant differences in differential renal function from baseline to post-captopril images in either group. CONCLUSIONS: Captopril induced a decrease in the GFR that could be quantitatively measured with 51Cr-EDTA. The reduction is more pronounced in hypertensive patients with RAS. PMID:20613937

Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit

2010-01-01

197

Effectiveness of diode laser trans-scleral cyclophotocoagulation in patients following silicone oil-induced ocular hypertension in Chinese eyes.  

PubMed

We evaluated the effectiveness of diode laser trans-scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in nine patients having raised IOP following use of silicone oil (SO) for retinal detachment (RD) surgery in a retrospective observational case series. Diode laser TSCPC was applied at a power setting of 1.75 to 2.5 watts, for two sec with a maximum of 30 applications. The patients were followed up for 40 to 312 weeks. The mean pre-laser IOP was 32.06 mm Hg (SD 7.32). The mean post-laser IOP at one month, three months and six months was 17.89 mm Hg (SD 8.23), 21.89 mm Hg (SD 8.16) and 21.67 mm Hg (SD 7.55) respectively. The final IOP (at the last follow-up) was 19.56 mm Hg (SD 7.85) (P=0.021). Seven of them had undergone SO removal. In our observation, effectiveness of TSCPC in long-term control of SO-induced ocular hypertension was limited as compared to short-term control of IOP. PMID:21157080

Gangwani, Rita; Liu, David T L; Congdon, Nathan; Lam, Philip T H; Lee, Vincent Y W; Yuen, Nancy S Y; Lam, Dennis S C

2011-01-01

198

Repeated administration of frusemide does not offer an advantage over single dosing in attenuating exercise-induced pulmonary hypertension in thoroughbred horses.  

PubMed

The objective of the present study was to ascertain whether administration of a second dose of frusemide would attenuate exercise-induced pulmonary hypertension more than a single dose. Right atrial, right ventricular and pulmonary vascular pressures were determined in 7 healthy, sound, exercise-trained Thoroughbred horses at rest and during exercise (14.2 m/s + a 3.5% uphill grade) performed at maximal heart rate (217 +/- 3 beats/min [mean +/- s.e.]). Horses were studied during the following 3 treatments in random order 7 days apart: control (no medication), frusemide single dose (250 mg i.v. 4 h pre-exercise), and frusemide double dose (250 mg i.v., 4 h pre-exercise + 250 mg i.v. 2 h pre-exercise). In the control study, exercise resulted in significant (P < 0.05) right atrial as well as pulmonary arterial, capillary and venous hypertension. In the frusemide single dose experiments, a significant (P < 0.05) attenuation of the exercise-induced rise in right atrial and pulmonary vascular pressures was observed. However, compared with frusemide single dose experiments, significant changes in the exercise-induced right atrial and pulmonary arterial, capillary and venous hypertension were not observed in the frusemide double dose experiments. Therefore, it is concluded that administration of an additional dose of frusemide is unlikely to affect the severity of EIPH in racing Thoroughbred horses more than a single dose. PMID:10659314

Goetz, T E; Manohar, M; Magid, J H

1999-07-01

199

Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension  

PubMed Central

Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) in response to an inflammatory perturbation. When human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and related to enhanced messenger RNA (mRNA) translation. The mechanism was associated with disruption of stress granule formation. Specifically, loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34–PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2?), and derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused donor controls revealed heightened PA expression of GM-CSF co-distributing with increased TNF and expanded populations of hematopoietic and endothelial GM-CSF receptor ? (GM-CSFR?)–positive cells. Moreover, a 3-wk infusion of GM-CSF in mice increased hypoxia-induced PAH, in association with increased perivascular macrophages and muscularized distal arteries, whereas blockade of GM-CSF repressed these features. Thus, reduced BMPR2 can subvert a stress granule response, heighten GM-CSF mRNA translation, increase inflammatory cell recruitment, and exacerbate PAH. PMID:24446489

Sawada, Hirofumi; Saito, Toshie; Nickel, Nils P.; Alastalo, Tero-Pekka; Glotzbach, Jason P.; Chan, Roshelle; Haghighat, Leila; Fuchs, Gabriele; Januszyk, Michael; Cao, Aiqin; Lai, Ying-Ju; Perez, Vinicio de Jesus; Kim, Yu-Mee; Wang, Lingli; Chen, Pin-I; Spiekerkoetter, Edda; Mitani, Yoshihide; Gurtner, Geoffrey C.; Sarnow, Peter

2014-01-01

200

Clenbuterol administration does not attenuate the exercise-induced pulmonary arterial, capillary or venous hypertension in strenuously exercising Thoroughbred horses.  

PubMed

The present study was carried out to ascertain whether beta2-adrenergic receptor stimulation with clenbuterol would attenuate the pulmonary arterial, capillary and venous hypertension in horses performing high-intensity exercise and, in turn, modify the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Experiments were carried out on 6 healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications) and the clenbuterol (0.8 pg/kg bwt, i.v.) treatments. The sequence of these treatments was randomised for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, right heart/pulmonary vascular pressures were determined at rest, sub-maximal exercise and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate and induced EIPH in all horses. In the control experiments, incremental exercise resulted in progressive significant increments in right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures and all horses experienced EIPH. Clenbuterol administration to standing horses caused tachycardia, but significant changes in mean right atrial or pulmonary vascular pressures were not observed. During exercise performed after clenbuterol administration, heart rate as well as right atrial and pulmonary arterial, capillary and wedge pressures also increased progressively with increasing work intensity. However, these values were not found to be statistically significantly different from corresponding data in the control study and the incidence of EIPH remained unaffected. Since clenbuterol administration also does not affect the transpulmonary pressure during exercise, it is unlikely that the transmural force exerted onto the blood-gas barrier of exercising horses is altered following i.v. clenbuterol administration at the recommended dosage. PMID:11093630

Manohar, M; Goetz, T E; Rothenbaum, P; Humphrey, S

2000-11-01

201

Continuous inhalation of carbon monoxide induces right ventricle ischemia and dysfunction in rats with hypoxic pulmonary hypertension.  

PubMed

We aimed to investigate the toxicity of carbon monoxide (CO) in rats with right ventricle (RV) remodeling induced by hypoxic pulmonary hypertension (PHT). A group of Wistar rats was exposed to 3-wk hypobaric hypoxia (H). A second group was exposed to 50 ppm CO for 1 wk (CO). A third group was exposed to chronic hypoxia including 50 ppm CO during the third week (H+CO). These groups were compared with controls. RV and left ventricle (LV) functions were assessed by echocardiography and transparietal catheterization. Ventricular perfusion was estimated with the fluorescent microsphere method. Results were confirmed by histology. PHT induced RV hypertrophy and function enhancement. In the H group, RV shortening fraction (RVSF; 71 +/- 12% vs. 41 +/- 2%) and RV end-systolic pressure (RVESP; 54 +/- 6 vs. 19 +/- 2 mmHg) were increased compared with controls. Moreover, myocardial perfusion was increased in the RV (36 +/- 2% vs. 22 +/- 2%) and decreased in the LV (64 +/- 3% vs. 78 +/- 2%). In the H+CO group, RVSF (45 +/- 3% vs. 71 +/- 12%) and RVESP (38 +/- 3 vs. 54 +/- 6 mmHg) were decreased compared with the H group. RV perfusion was decreased in the H+CO group compared with the H group (21 +/- 5% vs. 36 +/- 2%), and LV perfusion was increased (79 +/- 5% vs. 64 +/- 3%). PHT and RV hypertrophy were still present in the H+CO group, and fibroses localized in the RV were detected. Similar lesions were observed in an additional group exposed simultaneously to hypoxia and 50 ppm CO over 3 wk. We demonstrated that rats with established PHT were more sensitive to CO, which dramatically alters the RV adaptive response to PHT, leading to ischemic lesions. PMID:17483237

Gautier, Mathieu; Antier, Daniel; Bonnet, Pierre; Le Net, Jean-Loic; Hanton, Gilles; Eder, Veronique

2007-08-01

202

Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B  

PubMed Central

Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF-?B-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF-?B, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF-?B p65, TNF-?, IL-1?, IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases. PMID:24223475

Chen, Xingyong; Shi, Xiaogeng; Zhang, Xu; Lei, Huixin; Long, Simei; Su, Huanxing; Pei, Zhong; Huang, Ruxun

2013-01-01

203

An increase in adenosine-5'-triphosphate (ATP) content in rostral ventrolateral medulla is engaged in the high fructose diet-induced hypertension  

PubMed Central

Background The increase in fructose ingestion has been linked to overdrive of sympathetic activity and hypertension associated with the metabolic syndrome. The premotor neurons for generation of sympathetic vasomotor activity reside in the rostral ventrolateral medulla (RVLM). Activation of RVLM results in sympathoexcitation and hypertension. Neurons in the central nervous system are able to utilize fructose as a carbon source of ATP production. We examined in this study whether fructose affects ATP content in RVLM and its significance in the increase in central sympathetic outflow and hypertension induced by the high fructose diet (HFD). Results In normotensive rats fed with high fructose diet (HFD) for 12 weeks, there was a significant increase in tissue ATP content in RVLM, accompanied by the increases in the sympathetic vasomotor activity and blood pressure. These changes were blunted by intracisternal infusion of an ATP synthase inhibitor, oligomycin, to the HFD-fed animals. In the catecholaminergic-containing N2a cells, fructose dose-dependently upregulated the expressions of glucose transporter 2 and 5 (GluT2, 5) and the rate-limiting enzyme of fructolysis, ketohexokinase (KHK), leading to the increases in pyruvate and ATP production, as well as the release of the neurotransmitter, dopamine. These cellular events were significantly prevented after the gene knocking down by lentiviral transfection of small hairpin RNA against KHK. Conclusion These results suggest that increases in ATP content in RVLM may be engaged in the augmented sympathetic vasomotor activity and hypertension associated with the metabolic syndrome induced by the HFD. At cellular level, the increase in pyruvate levels via fructolysis is involved in the fructose-induced ATP production and the release of neurotransmitter. PMID:24467657

2014-01-01

204

Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats  

EPA Science Inventory

Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

205

Role of Extracellular Fluid Volume in Inducing or Aggravating Obstructive Sleep Apnea-hypopnea in Patients with Resistant Hypertension.  

E-print Network

??Accumulating evidence suggests that volume overload in drug-resistant hypertension (RH) may contribute to the high prevalence of obstructive sleep apnea-hypopnea (OSAH). Upon recumbency, leg fluid… (more)

Friedman, Oded

2010-01-01

206

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced hypertension: The beneficial effects of melatonin.  

PubMed

Objective: The purpose of the present study was to evaluate the effects of melatonin on biochemical and cardiovascular changes resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a polychlorinated dibenzo-para-dioxin.Methods: A total of 24 Sprague-Dawley rats were divided equally into the following four groups: (1) control group was administered with 0.5 mL corn oil by gavage and 0.5 cc vehicle of melatonin (proportionally nine parts physiological serum + one part ethyl alcohol) intraperitoneally for 4 weeks, (2) the melatonin group was given 5 mg/kg/day melatonin intraperitoneally for 4 weeks, (3) the TCDD group was given 500 ng/kg/day TCDD by gavage for 4 weeks and (4) the TCDD + melatonin group was given TCDD (500 ng/kg/day) by gavage and melatonin (5 mg/kg/day) intraperitoneally simultaneously for 4 weeks. Systolic blood pressure was evaluated by the tail-cuff method. Vascular responses to phenylephrine and acetylcholine were evaluated in the isolated thoracic aortas.Results: TCDD not only augmented the systolic blood pressure but also increased the contractile responses to phenylephrine in aorta. Melatonin reversed the blood pressure augmented by TCDD and decreased the contractile responses to phenylephrine in aorta. TCDD induced an increase in the malondialdehyde levels in kidney tissue and melatonin did not change it. Therefore, TCDD caused a decrease in glutathione levels in kidney tissues and melatonin reversed it.Conclusion: Present data demonstrated that TCDD may lead to an increase in blood pressure via increased renal oxidative stress and vascular reactivity. However, melatonin might ameliorate the blood pressure disturbed by TCDD in part by decreasing the oxidant activity induced by TCDD. PMID:23308013

Ilhan, Selcuk; Atessahin, Dilek; Atessahin, Ahmet; Mutlu, Emre; Onat, Elif; Sahna, Engin

2013-01-23

207

A pivotal role of the vascular endothelial growth factor signaling pathway in the formation of venous hypertension-induced dural arteriovenous fistulas.  

PubMed

Dural arteriovenous fistulas (DAVFs) are associated with venous hypertension. Numerous studies have revealed high expression levels of vascular endothelial growth factor (VEGF) in human DAVF specimens, as well as in animal models of experimental venous hypertension. The objective of the present study was to clarify whether the VEGF signaling pathway is important in the development of DAVFs. Rats (n=216) were randomly divided into six groups. In the rats from five groups (groups A and C-E, n=45 in each group; group B, n=12), experimental venous hypertension was induced by right common carotid artery (CCA)?external jugular vein (EJV) anastomosis, superior sinus occlusion and left transver sinus occlusion, while the remaining group (group F, n=24) underwent sham surgery. The rats in group A received a VEGF recombinant adenovirus injection into the distal section of the right EJV 30 min prior to anastomosis of the CCA and EJV. An equivalent control adenovirus was injected into the right EJV of group B rats prior to anastomosis. The rats in group C received no virus prior to anastomosis and no medicine subsequent to surgery. The group D rats were lavaged with Vatalanib, a VEGF receptor (VEGFR) inhibitor, and the group E rats were lavaged with an equal quantity of saline weekly following surgery. Six rats from groups A-E and one rat from group F were sacrificed in the first, second, fourth and twelfth weeks after surgery for immunohistochemical analysis of VEGF expression and analysis of microvessel density. Cerebral angiography was performed on the remaining rats in each group on the twelfth week after surgery. The results revealed that following transfection with VEGF recombinant adenovirus, angiogenesis in the dura mater of venous hypertensive rats was increased subsequent to the increase in the VEGF expression levels of the brain and dura mater. The rate of DAVF induction by venous hypertension was significantly reduced by the VEGFR antagonist due to reduced angiogenesis in the dura mater. In conclusion, VEGF and its receptor may be important in the formation of venous hypertension-induced DAVFs. PMID:24626343

Li, Qiang; Zhang, Qi; Huang, Qing-Hai; Fang, Yi-Bin; Zhang, Zhao-Long; Xu, Yi; Liu, Jian-Min

2014-05-01

208

Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats.  

PubMed

The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with high-salt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of ?-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms. PMID:24190226

Arima, Shiho; Uto, Hirofumi; Ibusuki, Rie; Kumamoto, Ryo; Tanoue, Shirou; Mawatari, Seiichi; Oda, Kohei; Numata, Masatsugu; Fujita, Hiroshi; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

2014-01-01

209

Upregulation of the Na(+)-K(+)-2Cl(-) cotransporter 1 via histone modification in the aortas of angiotensin II-induced hypertensive rats.  

PubMed

The Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is upregulated in diverse models of hypertension. We hypothesized that NKCC1 is upregulated via histone modification in the aortas of angiotensin II (Ang II)-induced hypertensive rats. An osmotic mini-pump containing Ang II was implanted in the subcutaneous tissues of the backs of Sprague-Dawley (SD) rats for 7 days. The systolic blood pressure was recorded every day by the tail-cuff method. On days 3 and 7, the mesenteric arteries were excised, cut into rings, mounted in organ baths and subjected to vascular contraction. The levels of Nkcc1 mRNA and protein in the aortas were measured using real-time PCR and Western blotting, respectively. The histone modifications and recruited proteins at the Nkcc1 promoter were determined by chromatin immunoprecipitation. The inhibition of concentration-response curves to phenylephrine by bumetanide, an inhibitor of NKCCs, was greater in Ang II-infused rats than in sham-operated (sham) rats . The levels of Nkcc1 mRNA and protein in the aortas increased gradually as Ang II was infused into the rats. Acetylated histone H3 (H3Ac), an activating histone code, was increased but trimethylated histone H3 at lysine 27 (H3K27me3), a repressive histone code, was greatly decreased in Ang II-infused rats compared with sham. RNA polymerase II was recruited to the Nkcc1 promoter with increased KDM6b. We conclude that the NKCC1 is upregulated via histone modification in the aortas of Ang II-induced hypertensive rats. Thus, we suggest that this ion transporter is epigenetically upregulated by histone modification or DNA demethylation upon the development of hypertension. PMID:22495607

Cho, Hyun-Min; Lee, Dong-Youb; Kim, Hye Young; Lee, Hae-Ahm; Seok, Young Mi; Kim, In Kyeom

2012-08-01

210

Pulmonary Oxidative Stress Is Increased in Cyclooxygenase-2 Knockdown Mice with Mild Pulmonary Hypertension Induced by Monocrotaline  

PubMed Central

The aim of this study was to examine the role of cyclooxygenase-2 (COX-2) and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH) using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD) mice, characterized by 80–90% suppression of COX-2, and wild-type (WT) control mice were treated weekly with monocrotaline (MCT) over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1) expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ?4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ?85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling. PMID:21850273

Seta, Francesca; Rahmani, Mahboubeh; Turner, Patricia V.; Funk, Colin D.

2011-01-01

211

Changes of Gene Expression after Bone Marrow Cell Transfusion in Rats with Monocrotaline-Induced Pulmonary Hypertension  

PubMed Central

Pulmonary artery hypertension (PAH) causes right ventricular failure and possibly even death by a progressive increase in pulmonary vascular resistance. Bone marrow-derived mesenchymal stem cell therapy has provided an alternative treatment for ailments of various organs by promoting cell regeneration at the site of pathology. The purpose of this study was to investigate changes of pulmonary haemodynamics, pathology and expressions of various genes, including ET (endothelin)-1, ET receptor A (ERA), endothelial nitric oxide synthase (NOS) 3, matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinase (TIMP), interleukin (IL)-6 and tumor necrosis factor (TNF)-? in monocrotaline (MCT)-induced PAH rat models after bone marrow cell (BMC) transfusion. The rats were grouped as the control (C) group, monocrotaline (M) group, and BMC transfusion (B) group. M and B groups received subcutaneous (sc) injection of MCT (60 mg/kg). BMCs were transfused by intravenous injection at the tail 1 week after MCT injection in B group. Results showed that the average RV pressure significantly decreased in the B group compared with the M group. RV weight and the ratio of RH/LH+septum significantly decreased in the B group compared to the M group. Gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-? significantly decreased in week 4 in the B group compared with the M group. In conclusion, BMC transfusion appears to improve survival rate, RVH, and mean RV pressure, and decreases gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-?. PMID:22690090

Kim, Kwan Chang; Lee, Hae Ryun; Kim, Sung Jin; Cho, Min-Sun

2012-01-01

212

Reduction of endoplasmic reticulum stress by 4-phenylbutyric acid prevents the development of hypoxia-induced pulmonary arterial hypertension.  

PubMed

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling of the pulmonary artery (PA). Recently, endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) have been disclosed in various types of diseases. Here we examined whether ER stress is involved in the pathogenesis of PAH. Four weeks of chronic normobaric hypoxia increased right ventricular (RV) systolic pressure by 63% compared with that in normoxic controls and induced RV hypertrophy and medial thickening of the PA in C57BL/6J mice. Treatment with 4-phenylbutyric acid (4-PBA), a chemical chaperone, significantly reduced RV systolic pressure by 30%, attenuated RV hypertrophy and PA muscularization, and increased total running distance in a treadmill test by 70% in hypoxic mice. The beneficial effects of 4-PBA were associated with suppressed expression of inflammatory cytokines and ER stress markers, including Grp78 and Grp94 in the activating transcription factor-6 branch, sXbp1 and Pdi in the inositol-requiring enzyme-1 branch and Atf4 in the PKR-like ER kinase branch, and reduced phosphorylation of c-Jun NH2-terminal kinase and eukaryotic translation initiation factor-2? in the lung. The pattern of changes in ER stress and inflammatory markers by 4-PBA in the lung of the PAH model was reproduced in PA smooth muscle cells by chronic stimulation of platelet-derived growth factor-BB or hypoxia. Furthermore, knockdown of each UPR branch sensor activated other branches and promoted proliferation of PA smooth muscle cells. The findings indicate that activation of all branches of the UPR and accompanying inflammation play a major role in the pathogenesis of PAH, and that chemical chaperones are potentially therapeutic agents for PAH. PMID:24610918

Koyama, Masayuki; Furuhashi, Masato; Ishimura, Shutaro; Mita, Tomohiro; Fuseya, Takahiro; Okazaki, Yusuke; Yoshida, Hideaki; Tsuchihashi, Kazufumi; Miura, Tetsuji

2014-05-01

213

Heme oxygenase-1 and inflammation in experimental right ventricular failure on prolonged overcirculation-induced pulmonary hypertension.  

PubMed

Heme oxygenase (HO)-1 is a stress response enzyme which presents with cardiovascular protective and anti-inflammatory properties. Six-month chronic overcirculation-induced pulmonary arterial hypertension (PAH) in piglets has been previously reported as a model of right ventricular (RV) failure related to the RV activation of apoptotic and inflammatory processes. We hypothesized that altered HO-1 signalling could be involved in both pulmonary vascular and RV changes. Fifteen growing piglets were assigned to a sham operation (n = 8) or to an anastomosis of the left innominate artery to the pulmonary arterial trunk (n = 7). Six months later, hemodynamics was evaluated after closure of the shunt. After euthanasia of the animals, pulmonary and myocardial tissue was sampled for pathobiological evaluation. Prolonged shunting was associated with a tendency to decreased pulmonary gene and protein expressions of HO-1, while pulmonary gene expressions of interleukin (IL)-33, IL-19, intercellular adhesion molecule (ICAM)-1 and -2 were increased. Pulmonary expressions of constitutive HO-2 and pro-inflammatory tumor necrosis factor (TNF)-? remained unchanged. Pulmonary vascular resistance (evaluated by pressure/flow plots) was inversely correlated to pulmonary HO-1 protein and IL-19 gene expressions, and correlated to pulmonary ICAM-1 gene expression. Pulmonary arteriolar medial thickness and PVR were inversely correlated to pulmonary IL-19 expression. RV expression of HO-1 was decreased, while RV gene expressions TNF-? and ICAM-2 were increased. There was a correlation between RV ratio of end-systolic to pulmonary arterial elastances and RV HO-1 expression. These results suggest that downregulation of HO-1 is associated to PAH and RV failure. PMID:23936023

Belhaj, Asmae; Dewachter, Laurence; Kerbaul, François; Brimioulle, Serge; Dewachter, Céline; Naeije, Robert; Rondelet, Benoît

2013-01-01

214

Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines.  

PubMed

The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5?g/h) or vehicle for 4weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1? and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. PMID:24342267

Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

2014-02-01

215

Tacrolimus-induced hypertension and nephrotoxicity in Fawn-Hooded rats are attenuated by dual inhibition of renin-angiotensin system.  

PubMed

Chronic immunosuppressive therapy is often complicated by the development of both arterial hypertension and renal dysfunction. The principal aim of this study was to assess the effects of dual inhibition of renin-angiotensin system (RAS) and other antihypertensive treatment on blood pressure and renal function in normotensive and hypertensive Fawn-Hooded (FH) strains during chronic calcineurin inhibitor (CNI) administration. Combinations of perindopril (5?mg?kg(-1) per day) and losartan (50?mg?kg(-1) per day) or amlodipine (6?mg?kg(-1) per day) and metoprolol (80?mg?kg(-1) per day) were administered to normotensive (FHL) and hypertensive (FHH) rats, fed with diet containing tacrolimus (Tac; 12?mg?kg(-1) per day). Tac-induced arterial hypertension in both animal strains (FHL: 151±4; FHH: 198±6?mm?Hg) was prevented by dual RAS inhibition (FHL: 132±3?mm?Hg, P<0.05; FHH: 153±3?mm?Hg, P<0.05) as well as by a combination of amlodipine and metoprolol (FHL: 136±3?mm?Hg, P<0.05; FHH: 166±4?mm?Hg, P<0.05). However, significant nephroprotection was observed only in animals on dual RAS inhibition where albuminuria was reduced in both FHL (51.1±3.9 vs. 68.3±4.5??g per day; P<0.05) and FHH rats (13.1±0.3 vs. 18.8±0.7?mg per day; P<0.05). We also found Tac-induced enhancement in renal angiotensin II activity that was significantly reduced by dual RAS inhibition in both FHL (63.5±3.2 vs. 23.1±3.0?fmol?g(-1)) and FHH (79.8±8.5 vs. 32.2±5.8?fmol?g(-1)). In addition, histological analysis revealed that RAS inhibition noticeably diminished glomerulosclerosis and tubulo-interstitial injury. This study indicates that dual blockade of RAS significantly attenuates Tac-induced arterial hypertension and nephrotoxicity in FH rats and further supports the notion that RAS inhibitors display efficient renoprotective properties during CNI treatment. PMID:24718302

Hošková, Lenka; Málek, Ivan; Kautzner, Josef; Honsová, Eva; van Dokkum, Richard P E; Husková, Zuzana; Vojtíšková, Alžbeta; Varcabová, Sárka; Cervenka, Lud?k; Kopkan, Libor

2014-08-01

216

Angiotensin II-Induced Hypertension Regulates AT1 Receptor Subtypes and Extracellular Matrix Turnover in Mouse Retinal Pigment Epithelium  

PubMed Central

Accumulation of specific deposits and extracellular molecules under the retinal pigment epithelium (RPE) have been previously observed in eyes with age-related macular degeneration (AMD) and may play a role in the pathogenesis of AMD. Even though age is the major determinant for developing AMD, clinical studies have revealed hypertension (HTN) as another systemic risk factor. Angiotensin II (Ang II) is considered the most important hormone associated with HTN. To evaluate the relationship of Ang II to AMD, we studied whether mouse RPE expresses functional Ang II receptor subtypes and whether HTN-induced Ang II regulates expression of these receptors as well as critical ECM molecules (MMP-2 and type IV collagen) involved in ECM turnover in RPE. We used 9 month-old C57BL/6 male mice infused with Ang II alone or Ang II in combination with the AT1 receptor antagonist candesartan or the AT2 receptor antagonist PD123319 for 4 weeks to determine whether HTN-associated Ang II was important for ECM regulation in RPE. We found that mouse RPE expressed both Ang II receptor subtypes at the mRNA and protein levels. Infusion with Ang II induced HTN and elevated plasma and ocular Ang II levels. Ang II also regulated AT1a and AT1b receptor mRNA expression, the intracellular concentration of calcium [Ca2+]i, MMP-2 activity, and type IV collagen accumulation. Concurrent administration of Ang II with the AT1 receptor blocker prevented the increase in blood pressure and rise in ocular Ang II levels, as well as the calcium and MMP-2 responses. In contrast, the type IV collagen response to Ang II was prevented by blockade of AT2 receptors, but not AT1 receptors. Plasma Ang II levels were not modified by the AT1 or AT2 receptor blockade. Since the effects of Ang II on MMP-2 and type IV collagen require inhibition of both Ang II receptor subtypes, these receptors may play a role as a potential therapeutic targets to prevent ECM turnover dysregulation in the RPE basement membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD. PMID:19281810

Praddaude, Francoise; Cousins, Scott W.; Pecher, Christiane; Marin-Castano, Maria E.

2009-01-01

217

Essential hypertension.  

PubMed

Essential hypertension can be defined as a rise in blood pressure of unknown cause that increases risk for cerebral, cardiac, and renal events. In industrialised countries, the risk of becoming hypertensive (blood pressure >140/90 mm Hg) during a lifetime exceeds 90%. Essential hypertension usually clusters with other cardiovascular risk factors such as ageing, being overweight, insulin resistance, diabetes, and hyperlipidaemia. Subtle target-organ damage such as left-ventricular hypertrophy, microalbuminuria, and cognitive dysfunction takes place early in the course of hypertensive cardiovascular disease, although catastrophic events such as stroke, heart attack, renal failure, and dementia usually happen after long periods of uncontrolled hypertension only. All antihypertensive drugs lower blood pressure (by definition) and this decline is the best determinant of cardiovascular risk reduction. However, differences between drugs exist with respect to reduction of target-organ disease and prevention of major cardiovascular events. Most hypertensive patients need two or more drugs for blood-pressure control and concomitant statin treatment for risk factor reduction. Despite the availability of effective and safe antihypertensive drugs, hypertension and its concomitant risk factors remain uncontrolled in most patients. PMID:17707755

Messerli, Franz H; Williams, Bryan; Ritz, Eberhard

2007-08-18

218

Obesity hypertension: role of leptin and sympathetic nervous system  

Microsoft Academic Search

Obesity may account for as much as 65% to 75% of human essential hypertension in most industrialized countries. Excess renal sodium reabsorption and a hypertensive shift of renal-pressure natriuresis play a key role in mediating obesity hypertension. Sympathetic activation contributes to obesity-induced sodium retention and hypertension because adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that

John E. Hall; Drew A. Hildebrandt; Jay Kuo

2001-01-01

219

Role of sympathetic nervous system and neuropeptides in obesity hypertension  

Microsoft Academic Search

Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium reten- tion and hypertension

J. E. Hall; M. W. Brands; D. A. Hildebrandt; J. Kuo; S. Fitzgerald

2000-01-01

220

Pioglitazone reduces angiotensin II-induced COX-2 expression through inhibition of ROS production and ET-1 transcription in vascular cells from spontaneously hypertensive rats.  

PubMed

Glitazones have anti-inflammatory properties by interfering with the transcription of proinflammatory genes, such as cyclooxygenase (COX)-2, and with ROS production, which are increased in hypertension. This study analyzed whether pioglitazone modulates COX-2 expression in hypertension by interfering with ROS and endothelin (ET)-1. In vivo, pioglitazone (2.5 mg·kg(-1)·day(-1), 28 days) reduced the greater levels of COX-2, pre-pro-ET-1, and NADPH oxidase (NOX) expression and activity as well as O2 (·-) production found in aortas from spontaneously hypertensive rats (SHRs). ANG II increased COX-2 and pre-pro-ET-1 levels more in cultured vascular smooth muscle cells from hypertensive rats compared with normotensive rats. The ETA receptor antagonist BQ-123 reduced ANG II-induced COX-2 expression in SHR cells. ANG II also increased NOX-1 expression, NOX activity, and superoxide production in SHR cells; the selective NOX-1 inhibitor ML-171 and catalase reduced ANG II-induced COX-2 and ET-1 transcription. ANG II also increased c-Jun transcription and phospho-JNK1/2, phospho-c-Jun, and p65 NF-?B subunit nuclear protein expression. SP-600125 and lactacystin, JNK and NF-?B inhibitors, respectively, reduced ANG II-induced ET-1, COX-2, and NOX-1 levels and NOX activity. Pioglitazone reduced the effects of ANG II on NOX activity, NOX-1, pre-pro-ET-1, COX-2, and c-Jun mRNA levels, JNK activation, and nuclear phospho-c-Jun and p65 expression. In conclusion, ROS production and ET-1 are involved in ANG II-induced COX-2 expression in SHRs, explaining the greater COX-2 expression observed in this strain. Furthermore, pioglitazone inhibits ANG II-induced COX-2 expression likely by interfering with NF-?B and activator protein-1 proinflammatory pathways and downregulating ROS production and ET-1 transcription, thus contributing to the anti-inflammatory properties of glitazones. PMID:24727493

Pérez-Girón, Jose V; Palacios, Roberto; Martín, Angela; Hernanz, Raquel; Aguado, Andrea; Martínez-Revelles, Sonia; Barrús, María T; Salaices, Mercedes; Alonso, María J

2014-06-01

221

Asiatic Acid Reduces Blood Pressure by Enhancing Nitric Oxide Bioavailability with Modulation of eNOS and p47(phox) Expression in l-NAME-induced Hypertensive Rats.  

PubMed

We investigated the effect of asiatic acid (AA) on hemodynamic status, vascular function, oxidative stress markers, endothelial nitric oxide synthase (eNOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression in N? -nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Male Sprague-Dawley rats treated with l-NAME (40?mg/kg/day) in drinking water for 5?weeks showed significant increases in mean arterial pressure, heart rate, hindlimb vascular resistance, vascular dysfunction, superoxide anion (O2 (•-) ) production, and plasma malondialdehyde. Moreover, NO metabolite (NOx) levels were reduced, aortic eNOS expression was downregulated, and NADPH oxidase subunit p47(phox) was upregulated in hypertensive rats (p?Hypertensive rats that were administered AA (10 or 20?mg/kg/day) for the last 2?weeks of the study showed significant improvement in hemodynamic status and vascular function. The antihypertensive effects of AA were associated with elevated plasma NOx levels, together with upregulation of eNOS expression. Decreased vascular O2 (•-) production, consistent with downregulation of p47(phox) expression, was also observed after AA treatment. Our results are therefore consistent with a model whereby AA reduces blood pressure by enhancing NO bioavailability. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24723332

Bunbupha, Sarawoot; Pakdeechote, Poungrat; Kukongviriyapan, Upa; Prachaney, Parichat; Kukongviriyapan, Veerapol

2014-10-01

222

Characterization of blood pressure and endothelial function in TRPV4-deficient mice with l-NAME- and angiotensin II-induced hypertension  

PubMed Central

Abstract Transient receptor potential vanilloid type 4 (TRPV4) is an endothelial Ca2+ entry channel contributing to endothelium?mediated dilation in conduit and resistance arteries. We investigated the role of TRPV4 in the regulation of blood pressure and endothelial function under hypertensive conditions. TRPV4?deficient (TRPV4?/?) and wild?type (WT) control mice were given l?NAME (0.5 g/L) in drinking water for 7 days or subcutaneously infused with angiotensin (Ang) II (600 ng/kg per minute) for 14 days, and blood pressure measured by radiotelemetry. TRPV4?/? mice had a lower baseline mean arterial pressure (MAP) (12?h daytime MAP, 94 ± 2 vs. 99 ± 2 mmHg in WT controls). l?NAME treatment induced a slightly greater increase in MAP in TRPV4?/? mice (day 7, 13 ± 4%) compared to WT controls (6 ± 2%), but Ang II?induced increases in MAP were similar in TRPV4?/? and WT mice (day 14, 53 ± 6% and 37 ± 11%, respectively, P < 0.05). Chronic infusion of WT mice with Ang II reduced both acetylcholine (ACh)?induced dilation (dilation to 10?5 mol/L ACh, 71 ± 5% vs. 92 ± 2% of controls) and the TRPV4 agonist GSK1016790A?induced dilation of small mesenteric arteries (10?8 mol/L GSK1016790A, 14 ± 5% vs. 77 ± 7% of controls). However, Ang II treatment did not affect ACh dilation in TRPV4?/? mice. Mechanistically, Ang II did not significantly alter either TRPV4 total protein expression in mesenteric arteries or TRPV4 agonist?induced Ca2+ response in mesenteric endothelial cells in situ. These results suggest that TRPV4 channels play a minor role in blood pressure regulation in l?NAME? but not Ang II?induced hypertension, but may be importantly involved in Ang II?induced endothelial dysfunction. PMID:24744878

Nishijima, Yoshinori; Zheng, Xiaodong; Lund, Hayley; Suzuki, Makoto; Mattson, David L.; Zhang, David X.

2014-01-01

223

Persistent perioperative tachycardia and hypertension diagnosed as thyroid storm induced by a hydatidiform mole: a case report  

PubMed Central

Thyroid storm is a critical complication of molar pregnancy. However, early diagnosis of it is difficult because it is a rare complication and usually presents nonspecific findings. In this case report, we present a woman with molar pregnancy who had persistent tachycardia and hypertension. She was diagnosed initially with preeclampsia and sepsis as complications of molar pregnancy. During dilation and curettage under general anesthesia with sevoflurane and remifentanil, tachycardia and hypertension remained even with continuous infusion of labetalol. The patient was subsequently diagnosed with thyroid storm associated with molar pregnancy. She was restored to a clinically euthyroid state 1 day after the operation, and her thyroid function test and ?-hCG values were normal 3 months later. The anesthesiologists should bear in mind the possibility of thyroid storm in patients with molar pregnancies who show persistent tachycardia and hypertension. PMID:25302097

Hwang, Wonjung; Im, Daehwan

2014-01-01

224

Role of protein kinase C beta in phorbol ester-induced c-fos gene expression in neurons of normotensive and spontaneously hypertensive rat brains.  

PubMed

We have previously demonstrated that pressure application of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) onto some neurons in the anterior hypothalamic area of rats increases neural activity in vivo and that this PKC activation-induced increase of neural activity is enhanced in spontaneously hypertensive rats (SHR), an animal model for genetic hypertension. Activation of PKC increases expression of the c-fos gene, an important transcription factor and proto-oncogene thought to be a marker of neural activity. To evaluate PKC isoforms responsible for neural activation, we examined which isoforms of PKC are involved in the PKC activation-induced c-fos gene expression in neuronal cultures of Wistar rat and spontaneously hypertensive rat (SHR) brains. PMA increased c-fos gene expression in neuronal cultures of Wistar rat brain and the PMA-induced c-fos gene expression was inhibited by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7). The PKCalpha,beta,gamma activator thymeleatoxin also increased c-fos gene expression, while the PKCdelta,epsilon activator ingenol did not affect it. In addition, the PMA-induced c-fos gene expression was inhibited by PKCbetaantisense oligonucleotides (AON) but not by PKCalpha and PKCgammaAONs. In SHR brain neuronal cultures, the PMA-induced c-fos gene expression was enhanced as compared with that of Wistar Kyoto rats (WKY), while basal c-fos gene expression was almost the same in both neuronal cultures. The enhancement of PMA-induced c-fos gene expression in SHR brain cultures was abolished by PKCbetaAON. These findings suggest that in rat brain neuronal cultures, PMA increases c-fos gene expression via activation of PKC and that PKCbetaisoforms are partly involved in the PMA-induced c-fos gene expression. In neuronal cultures of SHR brain, it appears that the PMA-induced c-fos gene expression is also enhanced via PKCbeta. PMID:15804434

Amemiya, Takahiro; Kambe, Toshie; Fukumori, Ryuji; Kubo, Takao

2005-04-01

225

Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension  

SciTech Connect

The balance between cell proliferation and cell quiescence is regulated delicately by a variety of mediators, in which cyclin-dependent kinases (CDK) and CDK inhibitors (CDKI) play a very important role. Heparin which inhibits pulmonary artery smooth muscle cell (PASMC) proliferation increases the levels of two CDKIs, p21 and p27, although only p27 is important in inhibition of PASMC growth in vitro and in vivo. In the present study we investigated the expression profile of all the cell cycle regulating genes, including all seven CDKIs (p21, p27, p57, p15, p16, p18, and p19), in the lungs of mice with hypoxia-induced pulmonary hypertension. A cell cycle pathway specific gene microarray was used to profile the 96 genes involved in cell cycle regulation. We also observed the effect of heparin on gene expression. We found that (a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p18 activity, showing a 98% decrease in p27 and 81% increase in p18; (b) other CDKIs, p21, p57, p15, p16, and p19 were not affected significantly in response to hypoxia; (c) heparin treatment restored p27 expression, but did not influence p18; (d) ERK1/2 and p38 were mediators in heparin upregulation of p27. This study provides an expression profile of cell cycle regulating genes under hypoxia in mice with hypoxia-induced pulmonary hypertension and strengthens the previous finding that p27 is the only CDKI involved in heparin regulation of PASMC proliferation and hypoxia-induced pulmonary hypertension.

Yu Lunyin [Department of Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (United States); Quinn, Deborah A. [Department of Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (United States); Garg, Hari G. [Department of Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (United States); Hales, Charles A. [Department of Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 (United States)]. E-mail: chales@partners.org

2006-07-14

226

Novel mechanism of intra?renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats.  

PubMed

The present study aimed to investigate the molecular pharmacodynamic mechanisms of losartan used in the treatment of hypertension. A total of 12 spontaneously hypertensive rats (SHR) were divided randomly into an SHR group treated with saline and LOS group treated with losartan. Six Wistar?kyoto rats (WKY) were enrolled as the WKY group with saline in the study. The LOS group received 30 mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the same volume of saline. The dosage was modulated according to the weekly weight. Changes in blood pressure were measured by the indirect tail cuff method. Angiotensin (Ang) II production in the plasma and renal tissue was measured by an immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid?inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction (qPCR) and western blot analysis. When compared with the WKY group, the blood pressure of the SHR and LOS groups were higher prior to treatment with losartan. Following two weeks, blood pressure was reduced and the trend continued to decrease over the following six weeks. The plasma and renal tissue levels of Ang II in the SHR and LOS groups were significantly higher than those in the WKY group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR group, and losartan reduced the expression of both of them. The results suggested that in hypertensive rats, the circular and tissue renin angiotensin systems were activated, and the increased Ang II stimulated the expression of NHE3 and SGK1, which was reduced by losartan. Therefore, the effects of losartan in hypertension may be associated with the Ang II?SGK1?NHE3 of intra?renal tissue. PMID:25119059

Fan, Xiaoqin; Liu, Kaishan; Cui, Wei; Huang, Jiongmei; Wang, Weina; Gao, Yuan

2014-11-01

227

Hypertension screening  

NASA Technical Reports Server (NTRS)

An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

Foulke, J. M.

1975-01-01

228

Pulmonary hypertension  

MedlinePLUS

... become larger. This condition is called right-sided heart failure, or cor pulmonale. Pulmonary hypertension may be caused ... heart Blood clots in the lung ( pulmonary embolism ) Heart failure Heart valve disease HIV infection Low oxygen levels ...

229

Neonatal Hypertension  

Microsoft Academic Search

\\u000a Hypertension as a clinical problem in newborn infants was first recognized in the 1970s (1). However, recent advances in our ability to identify, evaluate, and care for prmature infants have lead to an increased awareness\\u000a of neonatal hypertension, not only in the neonatal intensive care unit (NICU) but also in the neonatal follow-up clinic. This\\u000a chapter will focus on the

Joseph T. Flynn

230

Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure.  

PubMed

Pulmonary arterial hypertension (PAH) is a debilitating and deadly disease with no known cure. Heart failure is a major comorbidity and a common cause of the premature death of patients with PAH. Increased asymmetrical right ventricular hypertrophy and septal wall thickening compress the left ventricular cavity and elicit diastolic heart failure. In this study, we used the Sugen5416/hypoxia/normoxia-induced PAH rat to determine whether altered pyridine nucleotide signaling in the failing heart contributes to 1) increased oxidative stress, 2) changes in metabolic phenotype, 3) autophagy, and 4) the PAH-induced failure. We found that increased reactive oxygen species, metabolic maladaptation, and autophagy contributed to the pathogenesis of right ventricular remodeling and hypertrophy that lead to left ventricular diastolic dysfunction. In addition, arterial elastance increased in PAH rats. Glucose-6-phosphate dehydrogenase is a major source of pyridine molecule (nicotinamide adenine dinucleotide phosphate), which is a substrate for nicotinamide adenine dinucleotide phosphate oxidases in the heart. Dehydroepiandrosterone, a 17-ketosteroid that reduces pulmonary hypertension and right ventricular hypertrophy, inhibited glucose-6-phosphate dehydrogenase, decreased oxidative stress, increased glucose oxidation and acetyl-coA, and reduced autophagy in the hearts of PAH rats. It also decreased arterial stiffness and improved left ventricular diastolic function. These findings demonstrate that pyridine nucleotide signaling, at least partly, mediates PAH-induced diastolic heart failure, and that reduction of glucose-6-phosphate dehydrogenase-derived nicotinamide adenine dinucleotide phosphate is beneficial to improve left ventricle diastolic function. PMID:25267798

Rawat, Dhawjbahadur K; Alzoubi, Abdallah; Gupte, Rakhee; Chettimada, Sukrutha; Watanabe, Makino; Kahn, Andrea G; Okada, Takao; McMurtry, Ivan F; Gupte, Sachin A

2014-12-01

231

Systemic hypertension.  

PubMed

Hypertension is a growing public health problem worldwide. Only 37% of American hypertensives currently have their blood pressures controlled. Hypertension is traditionally diagnosed in the medical office, but both home and ambulatory blood pressure monitoring can help. Lifestyle modifications are recommended for everyone who has higher than "normal" blood pressure (<120/80 mm Hg). Voluminous clinical trial data support beginning drug therapy with low-dose chlorthalidone, unless the patient has a specific indication for a different drug. Additional drugs (typically in the sequence, angiotensin converting-enzyme inhibitor or angiotensin receptor blocker, calcium antagonist, beta-blocker, alpha-blocker, aldosterone antagonist, direct vasodilator, and centrally acting alpha(2)-agonist) can be added to achieve the blood pressure goal (usually <140/90 mm Hg, but <130/80 mm Hg for diabetics and those with chronic kidney disease). Special circumstances exist for treatment of hypertension in pregnancy, in childhood, in the elderly, and in both extremes of blood pressure (pre-hypertension or hypertensive emergencies). PMID:17398315

Elliott, William J

2007-04-01

232

Beneficial effects of a novel agonist of the adenosine A2A receptor on monocrotaline-induced pulmonary hypertension in rats  

PubMed Central

Background and Purpose Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance, right ventricular hypertrophy and increased right ventricular systolic pressure. Here, we investigated the effects of a N-acylhydrazone derivative, 3,4-dimethoxyphenyl-N-methyl-benzoylhydrazide (LASSBio-1359), on monocrotaline (MCT)-induced pulmonary hypertension in rats. Experimental Approach PAH was induced in male Wistar rats by a single i.p. injection of MCT (60 mg·kg?1) and 2 weeks later, oral LASSBio-1359 (50 mg·kg?1) or vehicle was given once daily for 14 days. Echocardiography was used to measure cardiac function and pulmonary artery dimensions, with histological assay of vascular collagen. Studies of binding to human recombinant adenosine receptors (A1, A2A, A3) and of docking with A2A receptors were also performed. Key Results MCT administration induced changes in vascular and ventricular structure and function, characteristic of PAH. These changes were reversed by treatment with LASSBio-1359. MCT also induced endothelial dysfunction in pulmonary artery, as measured by diminished relaxation of pre-contracted arterial rings, and this dysfunction was reversed by LASSBio-1359. In pulmonary artery rings from normal Wistar rats, LASSBio-1359 induced relaxation, which was decreased by the adenosine A2A receptor antagonist, ZM 241385. In adenosine receptor binding studies, LASSBio-1359 showed most affinity for the A2A receptor and in the docking analyses, binding modes of LASSBio-1359 and the A2A receptor agonist, CGS21680, were very similar. Conclusion and Implications In rats with MCT-induced PAH, structural and functional changes in heart and pulmonary artery were reversed by treatment with oral LASSBio-1359, most probably through the activation of adenosine A2A receptors. PMID:23530610

Alencar, Allan K N; Pereira, Sharlene L; Montagnoli, Tadeu L; Maia, Rodolfo C; Kummerle, Arthur E; Landgraf, Sharon S; Caruso-Neves, Celso; Ferraz, Emanuelle B; Tesch, Roberta; Nascimento, Jose H M; de Sant'Anna, Carlos M R; Fraga, Carlos A M; Barreiro, Eliezer J; Sudo, Roberto T; Zapata-Sudo, Gisele

2013-01-01

233

Prevention and reversal of isolation-induced systolic arterial hypertension in rats by treatment with beta-adrenoceptor antagonists.  

PubMed Central

1. Rats were made hypertensive by 5 days of continuous isolation in glass metabolic cages; in the text "hypertensive" means having a systolic blood pressure greater than 145 mmHg. 2. Daily intraperitoneal injections of either propranolol (5 mg/kg) or atenolol (5 mg/kg) reduced systolic blood pressure within 3 days and the systolic blood pressure remained low provided that the treatment was continued. 3. Treatment with metoprolol also lowered the systolic blood pressure of isolated rats but only when a larger dose (10 mg/kg) was given. 4. Systolic blood pressure returned to hypertensive levels following withdrawal of treatment after 15 days of isolation. However, following cessation of treatment after 27 days of isolation, the systolic blood pressure did not rise. 5. Rats given propranolol in the drinking water (intake equivalent to a daily dose of 5 mg/kg) before and during isolation did not develop hypertension. 6. The possibility that suppression of sympathetic function by the beta-adrenoceptor antagonists was responsible for these changes is discussed. PMID:32946

Bennett, T; Gardiner, S M

1979-01-01

234

Involvement of cytochrome P-450 1B1 in renal dysfunction, injury, and inflammation associated with angiotensin II-induced hypertension in rats  

PubMed Central

We investigated the contribution of cytochrome P-450 1B1 (CYP1B1) to renal dysfunction and organ damage associated with ANG II-induced hypertension in rats. ANG II (300 ng·kg?1·min?1) or vehicle were infused for 2 wk, with daily injections of a selective CYP1B1 inhibitor, 2,4,3?,5?-tetramethoxystilbene (TMS; 300 ?g/kg ip), or its vehicle. ANG II increased blood pressure and renal CYP1B1 activity that were prevented by TMS. ANG II also increased water intake and urine output, decreased glomerular filtration rate, increased urinary Na+ and K+ excretion, and caused proteinuria, all of which were prevented by TMS. ANG II infusion caused hypertrophy, endothelial dysfunction, and increased reactivity of renal and interlobar arteries to vasoconstrictor agents and renal vascular resistance and interstitial fibrosis as indicated by accumulation of ?-smooth muscle actin, fibronectin, and collagen, and inflammation as indicated by increased infiltration of CD-3+ cells; these effects were inhibited by TMS. ANG II infusion also increased production of reactive oxygen species (ROS) and activities of NADPH oxidase, ERK1/2, p38 MAPK, and c-Src that were prevented by TMS. TMS alone had no effect on any of the above parameters. These data suggest that CYP1B1 contributes to the renal pathophysiological changes associated with ANG II-induced hypertension, most likely via increased ROS production and activation of ERK1/2, p38 MAPK, and c-Src and that CYP1B1 could serve as a novel target for treating renal disease associated with hypertension. PMID:22088434

Jennings, Brett L.; Anderson, Larry J.; Estes, Anne M.; Fang, Xiao R.; Song, Chi Young; Campbell, William B.

2012-01-01

235

Stress-Induced Changes In C-Fos And Corticotropin Releasing Hormone Immunoreactivity In The Amygdala Of The Spontaneously Hypertensive Rat  

PubMed Central

The present study was undertaken to test the hypothesis that dysregulation of the amygdala contributes to the exaggerated autonomic response to stress in an animal model of essential hypertension. Spontaneously hypertensive (SHR) and normotensive Wistar male rats were chronically instrumented and exposed to 20 min of either air jet stress (AJS) or air noise alone (CON). AJS induced a significant increase in both heart rate and arterial pressure that was greater in the SHR. AJS induced a significant increase in c-Fos-like immunoreactivity (FLI) throughout the caudal-rostral extent of the basolateral, medial, and central (CEA) subnuclei of the amygdala. Differences in FLI between strains were localized to the rostral CEA and the SHR expressed significantly less FLI. AJS also induced a significant increase in the number of corticotrophin releasing hormone (CRH) positive neurons in the CEA. Differences between strains were localized to the caudal CEA and the number of CRH-positive cells was significantly greater in the SHR. The stress-induced increase in CRH-labeling in caudal CEA of the SHR was coupled to a greater increase in FLI in the rostral locus coeruleus (LC) of the SHR versus the Wistar. AJS also induced significant increases in FLI in several hypothalamus subnuclei, but no strain-related differences were identified. These results suggest for the first time that dysregulation of CRH-positive cells in the caudal CEA and reduced excitation and/or exaggerated inhibition of rostral CEA neurons may contribute to the exaggerated cardiovascular response to stress in the SHR, possibly through descending modulation of the rostral LC. PMID:20832430

Porter, Karen; Hayward, Linda F

2010-01-01

236

Stress-induced changes in c-Fos and corticotropin releasing hormone immunoreactivity in the amygdala of the spontaneously hypertensive rat.  

PubMed

The present study was undertaken to test the hypothesis that dysregulation of the amygdala contributes to the exaggerated autonomic response to stress in an animal model of essential hypertension. Spontaneously hypertensive (SHR) and normotensive Wistar male rats were chronically instrumented and exposed to 20 min of either air jet stress (AJS) or air noise alone (CON). AJS induced a significant increase in both heart rate and arterial pressure that was greater in the SHR. AJS induced a significant increase in c-Fos-like immunoreactivity (FLI) throughout the caudal-rostral extent of the basolateral, medial, and central (CEA) subnuclei of the amygdala. Differences in FLI between strains were localized to the rostral CEA and the SHR expressed significantly less FLI. AJS also induced a significant increase in the number of corticotrophin releasing hormone (CRH) positive neurons in the CEA. Differences between strains were localized to the caudal CEA and the number of CRH-positive cells was significantly greater in the SHR. The stress-induced increase in CRH labeling in caudal CEA of the SHR was coupled to a greater increase in FLI in the rostral locus coeruleus (LC) of the SHR versus the Wistar. AJS also induced significant increases in FLI in several hypothalamus subnuclei, but no strain-related differences were identified. These results suggest for the first time that dysregulation of CRH-positive cells in the caudal CEA and reduced excitation and/or exaggerated inhibition of rostral CEA neurons may contribute to the exaggerated cardiovascular response to stress in the SHR, possibly through descending modulation of the rostral LC. PMID:20832430

Porter, Karen; Hayward, Linda F

2011-01-20

237

Functional and morphological effects of laser-induced ocular hypertension in retinas of adult albino Swiss mice  

PubMed Central

Purpose To investigate the effects of laser photocoagulation (LP)-induced ocular hypertension (OHT) on the survival and retrograde axonal transport of retinal ganglion cells (RGC), as well as on the function of retinal layers. Methods Adult albino Swiss mice (35–45 g) received laser photocoagulation of limbal and episcleral veins in the left eye. Mice were sacrificed at 8, 17, 35, and 63 days. Intraocular pressure (IOP) in both eyes was measured with a Tono-Lab before LP and at various days after LP. Flash electroretinogram (ERG) scotopic threshold response (STR) and a- and b-wave amplitudes were recorded before LP and at various times after LP. RGCs were labeled with 10% hydroxystilbamidine methanesulfonate (OHSt) applied to both superior colliculi before sacrifice and in some mice, with dextran tetramethylrhodamine (DTMR) applied to the ocular stump of the intraorbitally transected optic nerve. Retinas were immunostained for RT97 or Brn3a. Retinas were prepared as whole-mounts and photographed under a fluorescence microscope. Labeled RGCs were counted using image analysis software, and an isodensity contour plot was generated for each retina. Results IOP increased to twice its basal values by 24 h and was maintained until day 5, after which IOP gradually declined to reach basal values by 1 wk. Similar IOP increases were observed in all groups. The mean total number of OHSt+ RGCs was 13,428±6,295 (n=12), 10,456±14,301 (n=13), 12,622±14,174 (n=21), and 10,451±13,949 (n=13) for groups I, II, III, and IV, respectively; these values represented 28%, 23%, 26%, and 22% of the values found in their contralateral fellow retinas. The mean total population of Brn3a+ RGCs was 24,343±5,739 (n=12) and 10,219±8,887 (n=9), respectively, for groups I and III; these values represented 49% and 20%, respectively, of the values found in their fellow eyes. OHT retinas showed an absence of OHSt+ and DTMR+ RGCs in both focal wedge-shaped and diffuse regions of the retina. By 1 wk, there was a discrepancy between the total number of surviving OHSt+ RGCs and Brn3a+ RGCs, suggesting that a large proportion of RGCs had impaired retrograde axonal transport. In the retinal areas lacking backlabeled RGCs, neurofibrillar staining revealed aberrant expression of RT97 within axons and RGC bodies characteristic of axotomy. Elevated IOP induced significant reductions in the registered ERG waves, including positive STR, a- and b-waves, that were observed by 24 h and remained throughout the period of study for the three groups analyzed. Conclusions LP of the perilimbal and episcleral veins resulted in OHT leading to a lack of retrograde axonal transport in approximately 75% of the original RGC population. This lack did not progress further between 8 and 63 days, and it was both focal (in sectors with the apex located in the optic disc) and diffuse within the retina. In addition, severe amplitude diminutions of the STR and a- and b-waves of the ERG appeared as early as 24 h after lasering and did not recover throughout the period of study, indicating that increased IOP results in severe damage to the innermost, inner nuclear, and outer nuclear layers of the retina. PMID:20011633

Salinas-Navarro, Manuel; Alarcon-Martinez, Luis; Valiente-Soriano, Francisco Javier; Ortin-Martinez, Arturo; Jimenez-Lopez, Manuel; Aviles-Trigueros, Marcelino; Villegas-Perez, Maria Paz; de la Villa, Pedro

2009-01-01

238

Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension  

PubMed Central

Background Levels of marinobufagenin (MBG), an endogenous bufadienolide Na/K-ATPase (NKA) inhibitor, increase in preeclampsia and in NaCl-sensitive hypertension. Methods We tested a 3E9 monoclonal anti-MBG antibody (mAb) for the ability to lower blood pressure (BP) in NaCl-sensitive hypertension and to reverse the preeclampsia-induced inhibition of erythrocyte NKA. Measurements of MBG were performed via immunoassay based on 4G4 anti-MBG mAb. Results In hypertensive Dahl-S rats, an intraperitoneal administration of 50 ?g/kg 3E9 mAb lowered BP by 40 mmHg and activated Na/K-pump in thoracic aorta by 51%. NaCl supplementation of pregnant rats (n = 16) produced a 37 mmHg increase in BP, a 3.5-fold rise in MBG excretion, and a 25% inhibition of the Na/K-pump in the thoracic aorta, compared with pregnant rats on a normal NaCl intake. In eight pregnant hypertensive rats, 3E9 mAb reduced the BP (25 mmHg) and restored the vascular Na/K-pump. In 14 patients with preeclampsia (mean BP, 126 ± 3 mmHg; 26.9 ± 1.4 years; gestational age, 37 ± 0.8 weeks), plasma MBG was increased three-fold and erythrocyte NKA was inhibited compared with that of 12 normotensive pregnant women (mean BP, 71 W 3 mmHg)(1.5 ± 0.1 vs. 3.1 ± 0.2 ?mol Pi/ml/h, respectively; P < .01). Ex-vivo 3E9 mAb restored NKA activity in erythrocytes from patients with preeclampsia. As compared with 3E9 mAb, Digibind, an affinity-purified antidigoxin antibody, was less active with respect to lowering BP in both hypertensive models and to restoration of NKA from erythrocytes from patients with preeclampsia. Conclusion Anti-MBG mAbs may be a useful tool in the studies of MBG in vitro and in vivo and may offer treatment of preeclampsia. PMID:19008721

Fedorova, Olga V.; Simbirtsev, Andrey S.; Kolodkin, Nikolai I.; Kotov, Alexander Y.; Agalakova, Natalia I.; Kashkin, Vladimir A.; Tapilskaya, Natalia I.; Bzhelyansky, Anton; Reznik, Vitaly A.; Frolova, Elena V.; Nikitina, Elena R.; Budny, Georgy V.; Longo, Dan L.; Lakatta, Edward G.; Bagrov, Alexei Y.

2008-01-01

239

Primary Pulmonary Hypertension  

MedlinePLUS

... ENews Home > Lung Disease > Primary Pulmonary Hypertension Primary Pulmonary Hypertension Primary pulmonary hypertension (PPH) is a rare lung ... Lung Association also provides patients with information about pulmonary arterial hypertension (PAH). In-Depth Resources Symptoms, Diagnosis and Treatment ...

240

Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic Wistar-Kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment.  

PubMed

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

Erejuwa, Omotayo O; Sulaiman, Siti A; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N S; Salleh, Md Salzihan Md; Gurtu, Sunil

2011-01-01

241

Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment  

PubMed Central

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

2011-01-01

242

Immune mechanisms in hypertension.  

PubMed

Low grade inflammation may have a key role in the pathogenesis of hypertension and cardiovascular disease. Several studies showed that both innate and adaptive immune systems may be involved, being T cells the most important players. Particularly, the balance between Th1 effector lymphocytes and Treg lymphocytes may be crucial for blood pressure elevation and related organ damage development. In the presence of a mild elevation of blood pressure, neo-antigens are produced. Activated Th1 cells may then contribute to the persistent elevation of blood pressure by affecting vasculature, kidney and perivascular fat. On the other hand, Tregs represent a lymphocyte subpopulation with an anti-inflammatory role, being their activity crucial for the maintenance of cardiovascular homeostasis. Indeed, Tregs were demonstrated to be able to protect from blood pressure elevation and from the development of organ damage, including micro and macrovascular alterations, in different animal models of genetic or experimental hypertension. In the vasculature, inflammation leads to vascular remodeling through cytokine activity, smooth muscle cell proliferation and oxidative stress. It is also known that a consistent part of ischemia-reperfusion-induced acute kidney injury is mediated by inflammatory infiltration and that Treg cell infusion have a protective role. Also the central nervous system has an important role in the maintenance of cardiovascular homeostasis. In conclusion, hypertension development involves chronic inflammatory process. Knowledge of cellular and molecular players in the progression of hypertension has dramatically improved in the last decade, by assessing the central role of innate and adaptive immunity cells and proinflammatory cytokines driving the development of target organ damage. The new concept of role of immunity, especially implicating T lymphocytes, will eventually allow discovery of new therapeutic targets that may improve outcomes in hypertension and cardiovascular or renal disease in humans and uncover an entirely novel approach in the treatment of hypertension and vascular disease. PMID:24446309

De Ciuceis, Carolina; Rossini, Claudia; La Boria, Elisa; Porteri, Enzo; Petroboni, Beatrice; Gavazzi, Alice; Sarkar, Annamaria; Rosei, Enrico Agabiti; Rizzoni, Damiano

2014-12-01

243

Full-length human chromogranin-A cardioactivity: myocardial, coronary, and stimulus-induced processing evidence in normotensive and hypertensive male rat hearts.  

PubMed

Plasma chromogranin-A (CgA) concentrations correlate with severe cardiovascular diseases, whereas CgA-derived vasostatin-I and catestatin elicit cardiosuppression via an antiadrenergic/nitric oxide-cGMP mediated mechanism. Whether these phenomena are related is unknown. We here investigated whether and to what extent full-length CgA directly influences heart performance and may be subjected to stimulus-elicited intracardiac processing. Using normotensive and hypertensive rats, we evaluated the following: 1) direct myocardial and coronary effects of full-length CgA; 2) the signal-transduction pathway involved in its action mechanism; and 3) CgA intracardiac processing after ?-adrenergic [isoproterenol (Iso)]- and endothelin-1(ET-1)-dependent stimulation. The study was performed by using a Langendorff perfusion apparatus, Western blotting, affinity chromatography, and ELISA. We found that CgA (1-4 nM) dilated coronaries and induced negative inotropism and lusitropism, which disappeared at higher concentrations (10-16 nM). In spontaneously hypertensive rats (SHRs), negative inotropism and lusitropism were more potent than in young normotensive rats. We found that perfusion itself, Iso-, and endothelin-1 stimulation induced intracardiac CgA processing in low-molecular-weight fragments in young, Wistar Kyoto, and SHR rats. In young normotensive and adult hypertensive rats, CgA increased endothelial nitric oxide synthase phosphorylation and cGMP levels. Analysis of the perfusate from both Wistar rats and SHRs of untreated and treated (Iso) hearts revealed CgA absence. In conclusion, in normotensive and hypertensive rats, we evidenced the following: 1) full-length CgA directly affects myocardial and coronary function by AkT/nitric oxide synthase/nitric oxide/cGMP/protein kinase G pathway; and 2) the heart generates intracardiac CgA fragments in response to hemodynamic and excitatory challenges. For the first time at the cardiovascular level, our data provide a conceptual link between systemic and intracardiac actions of full-length CgA and its fragments, expanding the knowledge on the sympathochromaffin/CgA axis under normal and physiopathological conditions. PMID:23751870

Pasqua, Teresa; Corti, Angelo; Gentile, Stefano; Pochini, Lorena; Bianco, Mimma; Metz-Boutigue, Marie-Hélène; Cerra, Maria Carmela; Tota, Bruno; Angelone, Tommaso

2013-09-01

244

The Effect of Amlodipine and Sildenafil on the NT-ProBNP Level of Patients with COPD-Induced Pulmonary Hypertension  

PubMed Central

Pulmonary hypertension (PH) is an important cause of heart failure in chronic obstructive pulmonary disease (COPD). The pro brain natriuretic peptide N-terminal (NT-proBNP) has been suggested as a noninvasive marker to evaluate ventricular function. However, there is no evidence to support the use of NT-proBNP in monitoring the benefits of vasodilators in COPD induced PH. Thus, we used NT-proBNP as a biomarker to evaluate the effect of oral vasodilators on cardiac function in COPD-induced PH. Forty clinically-stable PH patients were enrolled with history of COPD, normal left ventricular ejection-fraction (LVEF), right ventricular systolic pressure (RVSP) > 45 mmHg and baseline blood NT-proBNP levels >100 pg/mL. Patients were randomized into two groups, one group received sildenafil and second group were given amlodipine for two weeks. NT-proBNP and systolic pulmonary arterial pressure (systolic PA-pressure) were measured at the beginning and the end of study. Mean NT-proBNP level in the first group was 1297 ± 912 pg/mL before therapy and 554 ± 5 pg/mL after two weeks drug therapy, respectively. Similarly, in second group NT-proBNP level was 1657 ± 989 pg/mL and 646 ± 5 pg/mL before and after treatment. Amlodipine or sildenafil significantly reduced NT-proBNP levels in COPD-induced PH patients (p < 0.05). Our study shows that amlodipine and sildenafil have a similar effect on NT-proBNP levels. In both groups NT- proBNP levels were significantly reduced after treatment. Therefore, our findings support the potential benefits of treatment with vasodilators in COPD induced PH. Pulmonary hypertension, Chronic obstructive pulmonary disease, NT-proBNP, Amlodipine, Sildenafil PMID:24711842

Sharif-kashani, Babak; Hamraghani, Ali; Salamzadeh, Jamshid; Abbasi Nazari, Mohammad; Malekmohammad, Majid; Behzadnia, Neda; Fahimi, Fanak

2014-01-01

245

Peroxisome proliferator-activated receptor-? activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats  

Microsoft Academic Search

We investigated the effects of a high-fat (HF) diet and peroxisome proliferator-activated receptor (PPAR)-? activation on the intrarenal lipotoxicity associated with the renin–angiotensin system (RAS) and oxidative stress using spontaneously hypertensive (SHR) rats. Male SHR and Wistar–Kyoto (WKY) rats at 8 weeks of age were fed either a normal-fat diet or an HF diet without or with fenofibrate treatment for

Seok Joon Shin; Ji Hee Lim; Sungjin Chung; Dong-Ye Youn; Hyun Wha Chung; Hyung Wook Kim; Jeong-Hwa Lee; Yoon Sik Chang; Cheol Whee Park

2009-01-01

246

616. Protection of Monocrotaline-Induced Pulmonary Hypertension by Adeno-Associated Virus Vector-Mediated Interleukin10 Expression  

Microsoft Academic Search

Background: Inflammation in the pulmonary vasculature plays a pivotal role in the pathogenesis of primary pulmonary hypertension (PH). Interleukin (IL)-10, an antiinflammatory cytokine, exerts pleiotropic vasculoprotective effects by attenuating inflammatory responses, endothelial dysfunction, and smooth muscle cell proliferation. Adeno-associated virus (AAV) vectors can achieve sustained gene expression with minimal inflammatory and immune responses. We examined whether AAV-mediated IL-10 expression could

Takayuki Ito; Takashi Okada; Hiroshi Miyashita; Tatsuya Nomoto; Yoshikazu Maeda; Mutsuko Sarukawa; Masahisa Shimpo; Toru Yoshioka; Takashi Matsushita; Hiroaki Mizukami; Akihiro Kume; Keiji Yamamoto; Uichi Ikeda; Kazuyuki Shimada; Keiya Ozawa

2005-01-01

247

Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice  

PubMed Central

BACKGROUND AND PURPOSE The calcium-activated potassium channel KCa3.1 is expressed in the vascular endothelium where its activation causes endothelial hyperpolarization and initiates endothelium-derived hyperpolarization (EDH)-dependent dilatation. Here, we investigated whether pharmacological activation of KCa3.1 dilates skeletal muscle arterioles and whether myoendothelial gap junctions formed by connexin40 (Cx40) are required for EDH-type dilatations and pressure depressor responses in vivo. EXPERIMENTAL APPROACH We performed intravital microscopy in the cremaster muscle microcirculation and blood pressure telemetry in Cx40-deficient mice. KEY RESULTS In wild-type mice, the KCa3.1-activator SKA-31 induced pronounced concentration-dependent arteriolar EDH-type dilatations, amounting to ?40% of maximal dilatation, and enhanced the effects of ACh. These responses were absent in mice devoid of KCa3.1 channels. In contrast, SKA-31-induced dilatations were not attenuated in mice with endothelial cells deficient in Cx40 (Cx40fl/fl:Tie2-Cre). In isolated endothelial cell clusters, SKA-31 induced hyperpolarizations of similar magnitudes (by ?38 mV) in Cx40fl/fl:Tie2-Cre, ubiquitous Cx40-deficient mice (Cx40-/-) and controls (Cx40fl/fl), which were reversed by the specific KCa3.1-blocker TRAM-34. In normotensive wild-type and Cx40fl/fl:Tie2-Cre as well as in hypertensive Cx40-/- animals, i.p. injections of SKA-31 (30 and 100 mg·kg?1) decreased arterial pressure by ?32 mmHg in all genotypes. The depressor response to 100 mg·kg?1 SKA-31 was associated with a decrease in heart rate. CONCLUSIONS AND IMPLICATIONS We conclude that endothelial hyperpolarization evoked by pharmacological activation of KCa3.1 channels induces EDH-type arteriolar dilatations that are independent of endothelial Cx40 and Cx40-containing myoendothelial gap junctions. As SKA-31 reduced blood pressure in hypertensive Cx40-deficient mice, KCa3.1 activators may be useful drugs for severe treatment-resistant hypertension. PMID:23734697

Radtke, Josephine; Schmidt, Kjestine; Wulff, Heike; Kohler, Ralf; Wit, Cor

2013-01-01

248

Blood pressure and the susceptibility to renal damage after unilateral nephrectomy and L-NAME-induced hypertension in rats  

Microsoft Academic Search

BACKGROUND: Fawn-hooded hypertensive (FHH) rats carry several genes which\\u000a determine the susceptibility to develop renal damage, while renal damage\\u000a resistant August x Copenhagen Irish (ACI) rats do not. Kidneys from\\u000a heterozygous (FHH x ACI) F(1) rats, appear to be largely, but not\\u000a completely, protected after blood pressure elevation with\\u000a N(omega)-nitro-L-arginine methyl ester (L-NAME). We examined the role of\\u000a an increased

Dokkum van R. P. E; H. J. Jacob; A. P. Provoost

2000-01-01

249

Sex differences in primary hypertension  

PubMed Central

Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477

2012-01-01

250

Hypertension Subtypes among Hypertensive Patients in Ibadan  

PubMed Central

Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH), isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5%) and IDH (4.9% versus 4.7%) were more prevalent among females, ISH (10.1% versus 6.2%) was higher among males (P = 0.048). Female subjects were more obese (P < 0.0001) and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations. PMID:25389499

Salako, Babatunde L.; Ogunniyi, Adesola; Cooper, Richard S.

2014-01-01

251

Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure.  

PubMed

We examined the effects of thyroid hormones (THs) on left ventricular (LV) function and myocyte remodeling in rats with spontaneously hypertensive heart failure (SHHF). SHHF rats were treated with three different TH doses from 20-21 mo of age. In terminal experiments, LV function (as determined by echocardiography and catheterization) and isolated myocyte shape were examined in SHHF rat groups and age-matched Wistar-Furth control animals. Compared with Wistar-Furth rats, the ratio of alpha- to beta-myosin was reduced in untreated SHHF rats. The alpha-to-beta-myosin ratio increased in all TH groups, which suggests a reversal of the fetal gene program. Low-dose TH produced no changes in LV myocyte size or function, but high-dose TH produced signs of hyperthyroidism (e.g., increased heart weight, tachycardia). The chamber diameter-to-wall thickness ratio declined with increasing dose due to reduced chamber diameter and increased wall thickness. This resulted in a 38% reduction in LV systolic wall stress in the middle- and high-dose groups despite sustained hypertension. Isolated myocyte data indicated that chamber remodeling and reduced wall stress were due to a unique alteration in myocyte transverse shape (e.g., reduced major diameter and increased minor diameter). Based on our present understanding of ventricular remodeling and wall stress, we believe these changes are likely beneficial. Results suggest that TH may be an important regulator of myocyte transverse shape in heart disease. PMID:15604125

Thomas, Tracy A; Kuzman, James A; Anderson, Brent E; Andersen, Susan M K; Schlenker, Evelyn H; Holder, Maurice S; Gerdes, A Martin

2005-05-01

252

Vascular and antioxidant effects of an aqueous Mentha cordifolia extract in experimental N(G)-nitro-L-arginine methyl ester-induced hypertension.  

PubMed

The effect of an aqueous Mentha cordifolia (MC) extract on the haemodynamic status, vascular remodeling, function, and oxidative status in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was investigated. Male Sprague-Dawley rats were given L-NAME [50 mg/(kg body weight (BW) d)] in their drinking water for 5 weeks and were treated by intragastric administration with the MC extract [200 mg/(kgBWd)] for 2 consecutive weeks. Quercetin [25 mg/(kg BW d)] was used as a positive control. The effects of the MC extract on the haemodynamic status, thoracic aortic wall thickness, and oxidative stress markers were determined, and the vasorelaxant activity of the MC extract was tested in isolated mesenteric vascular beds in rats. Significant increases in the mean arterial pressure (MAP), heart rate (HR), hind limb vascular resistance (HVR), wall thickness, and cross-sectional area of the thoracic aorta, as well as oxidative stress markers were found in the L-NAME-treated group compared to the control (P < 0.05). MAP, HVR, wall thickness, cross-sectional area of the thoracic aorta, plasma malondialdehyde (MDA), and vascular superoxide anion production were significantly reduced in L-NAME hypersensitive rats treated with the MC extract or quercetin. Furthermore, the MC extract induced vasorelaxation in the pre-constricted mesenteric vascular bed with intact and denuded endothelium of normotensive and hypertensive rats. Our results suggest that the MC extract exhibits an antihypertensive effect via its antioxidant capacity, vasodilator property, and reduced vascular remodeling. PMID:24772821

Pakdeechote, Poungrat; Prachaney, Parichat; Berkban, Warinee; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Khrisanapant, Wilaiwan; Phirawatthakul, Yada

2014-01-01

253

Resistant hypertension.  

PubMed

A 53 year old woman with hypercholesterolemia treated with statins, with no history of cardiovascular disease, was referred to the Hypertension and Vascular Risk Unit for management of hypertension resistant to 4 antihypertensive agents at full doses. The patient had obesity, with a body mass index of 36.3kg/m(2) and office blood pressure 162/102mm Hg. Physical examination showed no data of interest. Analysis: glucose 120mg/dl, glycated Hb: 6.4%, albuminuria 68mg/g, kidney function and study of the renin angiotensin system and other biochemical parameters were normal. Echocardiography: left ventricular mass, 131g/m(2) (normal, <110g/m(2)). True resistant hypertension was confirmed by ambulatory monitoring of blood pressure during 24h (153/89mm Hg). Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4.1mmol/l) following the treatment. After 8 weeks, blood pressure was well controlled: office blood pressure 132/86mm Hg and 24h-ambulatory blood pressure: 128/79mm Hg. PMID:23827205

Armario, P; Oliveras, A; de la Sierra, A

2013-11-01

254

NF-?B pathway is involved in CRP-induced effects on pulmonary arterial endothelial cells in chronic thromboembolic pulmonary hypertension.  

PubMed

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombofibrotic obstruction of proximal pulmonary arteries. The cellular and molecular mechanisms underlying the pathogenesis remain incompletely understood, although we recently evidenced the potential involvement of the inflammatory marker C-reactive protein (CRP). We aimed to investigate the intracellular mechanisms induced by CRP in proximal pulmonary arterial endothelial cells (PAEC). PAEC were isolated from vascular material obtained during pulmonary endarterectomy. RNA was extracted from CRP-stimulated PAEC, and first-stand cDNA was generated. A RT(2) profiler PCR Array was used to evaluate the expression of 84 key genes related to NF-?B-mediated signal transduction. CRP-induced NF-?B activation was studied. The effects of pyrrolidine-dithio-carbamate ammonium (PDTC), an inhibitor of the NF-?B pathway, were investigated on CRP-induced adhesion of monocytes to PAEC, adhesion molecule expression, endothelin-1 (ET-1), interleukin-6 (IL-6), and von Willebrand factor (vWF) secretion. Compared with nonstimulated PAEC, serotonin receptor 2B was downregulated by 25%, inhibitor of NF-?B kinase subunit epsilon (IKBKE) by 30%, and toll-like receptor-4 and -6 by 18 and 39%, respectively, in CRP-stimulated PAEC. The transcription factor FOS was threefold upregulated. CRP induced RelA/NF-?Bp65 phosphorylation. PDTC dose dependently inhibited the adhesion of monocytes to CRP-stimulated PAEC. PDTC also inhibited the CRP-induced expression of ICAM-1 at the surface of PAEC. PDTC impaired the secretion of ET-1 by 18% and tended to inhibit the secretion of IL-6 by CRP-stimulated PAEC by 46%. PDTC did not inhibit the CRP-induced secretion of vWF. These results suggest an involvement of the NF-?B pathway in mediating different effects of CRP on proximal CTEPH-PAEC. PMID:24097561

Wynants, Marijke; Vengethasamy, Leanda; Ronisz, Alicja; Meyns, Bart; Delcroix, Marion; Quarck, Rozenn

2013-12-01

255

Postoperative hypertension following radical neck dissection  

PubMed Central

Baroreflex failure results in wide excursions of blood pressure and heart rate. We report two cases that developed severe postoperative hypertension after radical neck dissection. Carotid sinus denervation during neck dissection may be the cause of the reflex hypertension once general anesthesia-induced vasodilatation has ended. PMID:22345960

Prakash, Smita; Rapsang, Amy; Kumar, Suresh S; Bhatia, Parminder S; Gogia, Anoop R

2012-01-01

256

Impaired ?-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced K(Ca) channel activity.  

PubMed

?-Adrenoceptor (?-AR)-mediated relaxation plays an important role in the regulation of vascular tone. ?-AR-mediated vascular relaxation is reduced in various disease states and aging. We hypothesized that ?-AR-mediated vasodilatation is impaired in DOCA-salt hypertension due to alterations in the cAMP pathway. ?-AR-mediated relaxation was determined in small mesenteric arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses were determined in the presence of l-NNA and indomethacin, NO synthase inhibitor and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA) inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not abolish the difference in ISO-induced relaxation between the groups. Forskolin (adenylyl cyclase activator)-induced relaxation was similar between the groups. The inhibition of IK(Ca)/SK(Ca) channels (TRAM-34 plus UCL1684) or BK(Ca) channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SK(Ca) channel was decreased in DOCA-salt arteries. The expression of BK(Ca) channel ? subunit was increased whereas the expression of BK(Ca) channel ? subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BK(Ca) channel and negatively modulates its activity, was increased in DOCA-salt arteries. These results suggest that the impairment of ?-AR-mediated relaxation in DOCA-salt mesenteric arteries may be attributable to altered IK(Ca)/SK(Ca) and/or BK(Ca) channels activities rather than cAMP/PKA pathway. Impaired ?-AR-stimulated BK(Ca) channel activity may be due to the imbalance between its subunit expressions and RACK1 upregulation. PMID:22388053

Matsumoto, Takayuki; Szasz, Theodora; Tostes, Rita C; Webb, R Clinton

2012-05-01

257

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2  

SciTech Connect

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China); Wen Fuqiang, E-mail: wenfuqiang.scu@gmail.co [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041 (China)

2010-05-15

258

Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133+ progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats.  

PubMed

Although hypoxia is detrimental to most cell types, it aids survival of progenitor cells and is associated with diseases like cancer and pulmonary hypertension in humans. Therefore, understanding the underlying mechanisms that promote survival of progenitor cells in hypoxia and then developing novel therapies to stop their growth in hypoxia-associated human diseases is important. Here we demonstrate that the proliferation and growth of human CD133(+) progenitor cells, which contribute to tumorigenesis and the development of pulmonary hypertension, are increased when cultured under hypoxic conditions. Furthermore, glucose-6-phosphate dehydrogenase (G6PD) activity was increased threefold in hypoxic CD133(+) cells. The increased G6PD activity was required for CD133(+) cell proliferation, and their growth was arrested by G6PD inhibition or knockdown. G6PD activity upregulated expression of HIF1?, cyclin A, and phospho-histone H3, thereby promoting CD133(+) cell dedifferentiation and self-renewal and altering cell cycle regulation. When CD133(+) cells were cocultured across a porous membrane from pulmonary artery smooth muscle cells (PASMCs), G6PD-dependent H2O2 production and release by PASMCs recruited CD133(+) cells to the membrane, where they attached and expressed smooth muscle markers (?-actin and SM22?). Inhibition of G6PD reduced smooth muscle marker expression in CD133(+) cells under normoxia but not hypoxia. In vivo, CD133(+) cells colocalized with G6PD(+) cells in the perivascular region of lungs from rats with hypoxia-induced pulmonary hypertension. Finally, inhibition of G6PD by dehydroepiandrosterone in pulmonary arterial hypertensive rats nearly abolished CD133(+) cell accumulation around pulmonary arteries and the formation of occlusive lesions. These observations suggest G6PD plays a key role in increasing hypoxia-induced CD133(+) cell survival in hypertensive lungs that differentiate to smooth muscle cells and contribute to pulmonary arterial remodeling during development of pulmonary hypertension. PMID:25063801

Chettimada, Sukrutha; Joshi, Sachindra Raj; Alzoubi, Abdallah; Gebb, Sarah A; McMurtry, Ivan F; Gupte, Rakhee; Gupte, Sachin A

2014-10-01

259

Neonatal hypertension.  

PubMed

The incidence of neonatal hypertension (HTN) remains low, at less than 2%, and its etiology is varied. Strict definitions of HTN in neonates are unavailable, and the decision to treat is based on opinion rather than evidence. More studies are needed to define normal blood pressure in neonates and to refine current reference values, thus permitting a better definition of HTN. Most causes of neonatal HTN, the most common of which seems to be renovascular disease, are determined by history and basic clinical investigations. Treatment is guided by clinical judgment and expert opinion, given the limited number of clinical trials. PMID:25155725

Batisky, Donald L

2014-09-01

260

Broiler breeder survivors of chronic unilateral pulmonary artery occlusion produce progeny resistant to pulmonary hypertension syndrome (ascites) induced by cool temperatures.  

PubMed

Chronic occlusion of one pulmonary artery triggers a high incidence of pulmonary hypertension syndrome (PHS, ascites) in broilers. In the present study, the left pulmonary artery was chronically occluded in 295 male and 255 female chicks pedigreed from 18 sire families, leading to PHS in 74% of the males and 45% of the females. Survivors were reared to breeding age and served as parents for the resulting PHS-resistant chicks (Resistant), whereas control chicks were produced from the base population for this line (Base). In two experiments, male and female Resistant and Base chicks were reared separately by sex but mixed by group within environmental chambers, where they were exposed to cool (14 C) temperatures. In both experiments, the incidence of PHS was at least 50% lower in the Resistant males and females than in the Base males and females, respectively. When compared within a sex, the Base and Resistant broilers surviving to the end of both experiments did not differ in final body weight or body weight gain, nor did their right:total ventricular weight (RV:TV) ratios differ. These results demonstrate that broiler breeders capable of thriving after having their entire cardiac output forced to flow through one lung, subsequently produced male and female progeny with substantially improved resistance to the onset of PHS induced by fast growth and exposure to cool environmental temperatures. Fast growth and cool temperatures are primary triggers for PHS under most conditions of commercial broiler growout. In both experiments, final necropsies revealed higher RV:TV ratios in ascitic than in nonascitic broilers, whereas normalizing the left ventricle plus septum weight for differences in body weight generated similar values for ascitic and nonascitic males or females, respectively. These results support a primary role for pulmonary hypertension but not cardiomyopathy in the pathogenesis of ascites triggered by cool temperatures in both the Base and Resistant populations. PMID:10090268

Wideman, R F; French, H

1999-03-01

261

Atomoxetine-induced increases in monoamine release in the prefrontal cortex are similar in spontaneously hypertensive rats and Wistar-Kyoto rats.  

PubMed

Spontaneously hypertensive rats (SHRs) are used as a model for attention-deficit/hyperactivity disorder (ADHD), since SHRs are hyperactive and show defective sustained attention in behavioral tasks. The psychostimulants amphetamine and methylphenidate and the selective norepinephrine reuptake inhibitor atomoxetine are used as ADHD medications. The effects of high K(+) stimulation or psychostimulants on brain norepinephrine or dopamine release in SHRs have been previously studied both in vitro and in vivo, but the effects of atomoxetine on these neurotransmitters have not. The present study examined the effects of administration of atomoxetine on extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex of juvenile SHRs and Wistar-Kyoto (WKY) rats. Baseline levels of prefrontal norepinephrine, dopamine, and serotonin were similar in SHRs and WKY rats. Systemic administration of atomoxetine (3 mg/kg) induced similar increases in prefrontal norepinephrine and dopamine, but not serotonin, levels in both strains. Furthermore, there was no difference in high K(+)-induced increases in extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex between SHRs and WKY rats. These findings indicate that monoamine systems in the prefrontal cortex are similar between SHRs and WKY rats. PMID:24634253

Ago, Yukio; Umehara, Masato; Higashino, Kosuke; Hasebe, Shigeru; Fujita, Kazumi; Takuma, Kazuhiro; Matsuda, Toshio

2014-05-01

262

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats  

SciTech Connect

Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)] [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

2011-05-06

263

Baroreflex hypertension therapy for resistant hypertension  

Microsoft Academic Search

At least 10% of all patients with hypertension are resistant to existing therapies. These patients are at increased risk of cardiovascular events and progressive kidney disease. In the face of uncontrolled hypertension, alternative therapies are needed. A device based Baroreflex Hypertension Therapy (BHT) is being developed to treat these patients. This therapy works by electrically activating the carotid baroreflex. The

D. A. Sica; R. S. Kieval; R. C. Martin; E. D. Irwin

2005-01-01

264

Resolution of pulmonary hypertension and other features induced by chronic hypoxia in rats during complete and intermittent normoxia.  

PubMed Central

Rats subjected to 10% O2 (hypoxic rats) for various periods and recovery regimens were compared with control animals with respect to pulmonary artery pressure (Ppa), right ventricular hypertrophy (RVH), and muscularisation of small pulmonary vessels. Mean Ppa was measured in anaesthetised animals spontaneously breathing air and rose from 16 mmHg in controls to 36 mmHg in rats exposed to hypoxia for three weeks. Ppa had returned to normal after 20 weeks' recovery in air. RVH regressed a little more quickly, but muscularisation of small pulmonary vessels. Mean Ppa was measured in anaesthetised animals spontaneously breathing air and rose from 16 mmHg in controls to 36 mmHg in rats exposed to hypoxia for three weeks. Ppa had returned to normal after 20 weeks' recovery in air. RVH regressed a little more quickly, but muscularisation of small pulmonary vessels was still apparent after 20 weeks. Some hypoxic rats were subjected to an intermittent normoxic recovery regimen for either 40 or 80 hours a week in air, the remainder in 10% O2. Some reduction in RVH probably occurred after six weeks on the 80-hour regimen, but there was no reduction in Ppa or muscularisation of small pulmonary vessels. These results suggest that the pulmonary hypertension of chronic alveolar hypoxia resolves very slowly and is probably related to structural changes in the pulmonary vessels. Their relevance to human cor pulmonale and intermittent long-term oxygen treatment for these patients is discussed. PMID:151344

Herget, J; Suggett, A J; Leach, E; Barer, G R

1978-01-01

265

Correlation of bevacizumab-induced hypertension and outcome in the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection  

PubMed Central

Background: Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer, but to date, despite extensive research, no predictive or prognostic biomarkers for bevacizumab have been identified. The development of bevacizumab-induced arterial hypertension has recently been suggested as a potential predictive biomarker. Methods: Blood pressure was recorded during the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection. In this analysis, the development of bevacizumab-induced hypertension was correlated with clinical outcomes. Results: Fifteen percent of patients developed ?grade 1 hypertension while receiving neoadjuvant chemotherapy, and 4% developed grade 3 hypertension. There was no correlation between the development of hypertension and radiological response rate (P=0.642), progression-free survival (P=0.644) or overall survival (P=0.480) in those who developed hypertension compared with those who did not. Conclusion: Bevacizumab-induced hypertension did not predict radiological response or survival in our study. The results highlight a number of important issues regarding the use of hypertension as a biomarker. PMID:22531628

Dewdney, A; Cunningham, D; Barbachano, Y; Chau, I

2012-01-01

266

Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II-induced hypertensive mice.  

PubMed

NAD(P)H oxidase (Nox)2 and Nox4 are the isoforms of Nox expressed in the macula densa (MD). MD-derived superoxide (O??), primarily generated by Nox2, is enhanced by acute ANG II stimulation. However, the effects of chronic elevations in ANG II during ANG II-induced hypertension on MD-derived O?? are unknown. We infused a slow pressor dose of ANG II (600 ng·min?¹·kg?¹) for 2 wk in C57BL/6 mice and found that mean arterial pressure was elevated by 22.3 ± 3.4 mmHg (P < 0.01). We measured O?? generation in isolated and perfused MDs and found that O?? generation by the MD was increased from 9.4 ± 0.9 U/min in control mice to 34.7 ± 1.8 U/min in ANG II-induced hypertensive mice (P < 0.01). We stimulated MMDD1 cells, a MD-like cell line, with ANG II and found that O?? generation increased from 921 ± 91 to 3,687 ± 183 U·min?¹·10? cells?¹, which was inhibited with apocynin, oxypurinol, or NS-398 by 46%, 14%, and 12%, respectively. We isolated MD cells using laser capture microdissection and measured mRNA levels of Nox. Nox2 and Nox4 levels increased by 3.7 ± 0.17- and 2.6 ± 0.15-fold in ANG II-infused mice compared with control mice. In MMDD1 cells treated with Nox2 or Nox4 small interfering (si)RNAs, ANG II-stimulated O?? generation was blunted by 50% and 41%, respectively. In cells treated with p22(phox) siRNA, ANG II-stimulated O?? generation was completely blocked. In conclusion, we found that a subpressor dose of ANG II enhances O?? generation in the MD and that the sources of this O?? are primarily Nox2 and Nox4. PMID:24285500

Zhang, Jie; Chandrashekar, Kiran; Lu, Yan; Duan, Yanhua; Qu, Phillip; Wei, Jin; Juncos, Luis A; Liu, Ruisheng

2014-02-01

267

An Interaction of Renin-Angiotensin and Kallikrein-Kinin Systems Contributes to Vascular Hypertrophy in Angiotensin II-Induced Hypertension: In Vivo and In Vitro Studies  

PubMed Central

The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R) contributes to vascular hypertrophy in angiotensin II (ANG II)–induced hypertension, through a mechanism involving reactive oxygen species (ROS) generation and extracellular signal-regulated kinase (ERK1/2) activation. Male Wistar rats were infused with vehicle (control rats), 400 ng/Kg/min ANG II (ANG II rats) or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg9-Leu8-bradykinin (ANGII+DAL rats), via osmotic mini-pumps (14 days) or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats). After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg) 184±5.9 vs 115±2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE): 21.8±2.7 vs 6.0±1.8] and ERK1/2 phosphorylation (% of control: 218.3±29.4 vs 100±0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17±3.1) and ERK1/2 phosphorylation (137±20.7%) in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC) stimulated with low concentrations (0.1 nM) of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM), B1R antagonist (10 µM) and Tiron (superoxide anion scavenger, 10 mM). These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth. Our findings highlight an important cross-talk between the DABK and ANG II in the vascular system and contribute to a better understanding of the mechanisms involved in vascular remodeling in hypertension. PMID:25369284

Ceravolo, Graziela S.; Montezano, Augusto C.; Jordao, Maria T.; Akamine, Eliana H.; Costa, Tiago J.; Takano, Ana P.; Fernandes, Denise C.; Barreto-Chaves, Maria L.; Laurindo, Francisco R.; Tostes, Rita C.; Fortes, Zuleica B.; Chopard, Renato P.; Touyz, Rhian M.; Carvalho, Maria Helena C.

2014-01-01

268

Adrenergic genetic mechanisms in hypertension and hypertensive kidney disease.  

PubMed

Catecholamine secretory traits were significantly heritable, as were stress-induced blood pressure changes. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis. In the tyrosine hyroxylase promoter, significant associations were found for urinary catecholamine excretion and for blood pressure response to stress. TH promoter haplotype 2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, 2 independent case-control studies (1,266 subjects with 53% women and 927 subjects with 24% women) replicated the effect of C-824T in the determination of blood pressure. Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in the storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive kidney disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed such regulatory regions as the proximal promoter and 3'-UTR. In chromaffin cell-transfected CHGA 3'-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3'-UTR displayed statistical associations with hypertension and hypertensive end stage renal disease. Therefore, I would like to review the common genetic variation in TH and CHGA as a cause of inter-individual variation in sympathetic activity, and ultimately blood pressure and hypertensive kidney disease. PMID:23946762

Kang, Sun Woo

2013-06-01

269

Effects of an Endothelin Receptor Antagonist on a Model of Hypertensive Retinopathy  

Microsoft Academic Search

Hypertensive retinopathy manifests itself as progressive retinal microvascular pathology in response to aberrant blood flow. The current study sought to evaluate whether dysfunction of the vasoactive endothelin-1 (ET-1) system is involved in the pathogenesis of hypertension-induced retinopathy in an animal model of systemic hypertension. The endothelin receptor antagonist, bosentan, was administered to spontaneously hypertensive rats (SHRs) and comparisons were made

Louise McDonald; Graham R. Lee; Tanyth E. deGooyer; Denise McDonald; Paul Canning; Elizabeth J. Kelso; Barbara J. McDermott; Alan W. Stitt

2010-01-01

270

Fosinopril prevents hyperfiltration and decreases proteinuria in post-transplant hypertensives  

Microsoft Academic Search

Fosinopril prevents hyperfiltration and decreases proteinuria in post-transplant hypertensives. Hypertension and renal mass reduction induce glomerular hypertension (GH), hyperfiltration (HF) and renal injury. GH may contribute to allograft loss in post-transplant hypertensive patients (PT × HT). HF and GH may be evaluated by renal response to acute protein intake (API). Since ACE inhibition may prevent GH, the effects of fosinopril

Tommaso Bochicchio; Guadalupe Sandoval; Oscar Ron; Héctor Pérez-Grovas; Javier Bordes; Jaime Herrera-Acosta

1990-01-01

271

Apelin and pulmonary hypertension  

PubMed Central

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin and the G-protein coupled apelin receptor (APLNR) are expressed in several tissues throughout the organism. Apelin is localized in vascular endothelial cells while the APLNR is localized in both endothelial and smooth muscle cells in vessels and in the heart. Apelin is regulated by hypoxia inducible factor -1? and bone morphogenetic protein receptor-2. Patients with PAH have lower levels of plasma-apelin, and decreased apelin expression in pulmonary endothelial cells. Apelin has therefore been proposed as a potential biomarker for PAH. Furthermore, apelin plays a role in angiogenesis and regulates endothelial and smooth muscle cell apoptosis and proliferation complementary and opposite to vascular endothelial growth factor. In the systemic circulation, apelin modulates endothelial nitric oxide synthase (eNOS) expression, induces eNOS-dependent vasodilatation, counteracts angiotensin-II mediated vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting potential new therapeutic target for PH. PMID:22140623

Andersen, Charlotte U.; Hilberg, Ole; Mellemkjær, Søren; Nielsen-Kudsk, Jens E.; Simonsen, U.

2011-01-01

272

Attenuation of alpha-adrenergic-induced vasoconstriction by dietary wild blueberries (Vaccinium angustifolium) is mediated by the NO-cGMP pathway in spontaneously hypertensive rats (SHRs).  

PubMed

The role of wild blueberries (WB) on key signaling steps of nitric oxide (NO) and cyclooxygenase (COX) pathways was examined in spontaneously hypertensive rats (SHRs) after eight weeks on a control (C) or an 8% w/w WB diet. Aortic rings from SHRs were stimulated with phenylephrine (Phe) in the absence or presence of inhibitors of: soluble guanylyl cyclase (sGC), phosphodiesterase-5 (PDE(5)), prostaglandin I(2) (PGI(2)) synthase and thromboxane A(2) (TXA(2)) synthase. Additionally, enzymatic activities in these pathways were determined by the concentration of NO, cyclic guanosine monophosphate (cGMP), PGI(2) and TXA(2). In the WB-fed SHR, attenuation of Phe-induced vasoconstriction was mediated by an increased synthesis or preservation of cGMP. Despite an increased release of PGI(2) in the WB group, neither inhibition of PGI(2) or TXA(2) synthase resulted in a different response to Phe between the control and the WB rings. Hence, in the SHR, WB decrease Phe-mediated vasoconstriction under basal conditions by enhancing NO-cGMP signaling without a significant involvement of the COX pathway. PMID:23944991

Kristo, Aleksandra S; Kalea, Anastasia Z; Schuschke, Dale A; Klimis-Zacas, Dorothy

2013-12-01

273

Hyperreninemic hypertension secondary to radiation nephritis in a child  

SciTech Connect

Radiation injury to the kidney, first reported almost eighty years ago, may vary from subclinical changes in renal blood flow or enzyme activity to clinically significant hypertension and/or renal failure. A child with radiation-induced hyperreninemic hypertension was cured by nephrectomy. The microscopic, subclinical, and clinical changes of irradiation injury are reviewed. The etiology of radiation-induced hypertension, methods of radioprotection, and early detection of radiation renal damage are discussed.

Hulbert, W.C. Jr.; Ettinger, L.J.; Wood, B.P.; Anderson, V.M.; Putnam, T.C.; Rabinowitz, R.

1985-08-01

274

Granulocyte colony-stimulating factor attenuates monocrotaline-induced pulmonary hypertension by upregulating endothelial progenitor cells via the nitric oxide system  

PubMed Central

Granulocyte colony-stimulating factor (G-CSF) has exhibited efficacy at preventing the progression of pulmonary hypertension (PH); however, the exact mechanism is not completely clear. The aim of the present study was to assess whether this protective effect was mediated by the upregulation of circulating endothelial progenitor cells (EPCs) via the nitric oxide (NO) system. PH was induced in male Sprague-Dawley (SD) rats by the administration of a single subcutaneous injection of monocrotaline (MCT). The rats were treated with recombinant human G-CSF (rhG-CSF, 50 ?g/kg/day) by subcutaneous injection from day five to day seven subsequent to the injection of MCT. N?-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg/day) was intragastrically administered in addition to rhG-CSF as a negative intervention. The changes in hemodynamics and histology, the number and function of circulating EPCs and the concentration of plasma NO were evaluated. With the occurrence of PH in the rat model, the number and function of circulating EPCs were demonstrated to be markedly downregulated. Moreover, a reduced plasma concentration of NO was observed, which was positively correlated with the number of circulating EPCs. Administration of rhG-CSF elevated the plasma level of NO, upregulated the number and function of circulating EPCs and effectively improved pulmonary hemodynamics and vascular reconstruction. Furthermore, the positive correlation between the levels of plasma NO and circulating EPCs was also observed in the rhG-CSF treatment group. However, the protective effect of rhG-CSF in PH was attenuated by L-NAME, which mediated the downregulation of NO and the EPCs. Thus, the present study suggests that G-CSF may attenuate the progression of MCT-induced PH by improving vascular injury repair mechanisms via the NO-mediated upregulation of EPCs. PMID:24255669

LIU, JUN-FENG; DU, ZHONG-DONG; CHEN, ZHI; HAN, ZHONG-CHAO; HE, ZHI-XU

2013-01-01

275

Synergistic vascular protective effects of combined low doses of PPAR? and PPAR? activators in angiotensin II-induced hypertension in rats  

PubMed Central

Background and Purpose: Protective cardiovascular effects of peroxisome proliferator activated receptor (PPAR)? and PPAR? activators have been demonstrated. If used as vasoprotective agents in high risk vascular patients rather than for their metabolic benefits, these agents could be associated with unwanted side effects. As a proof of concept to support the use of combined low doses of PPAR? and PPAR? as vascular protective agents in high risk vascular patients, we tested the hypothesis that combined low doses of PPAR? (fenofibrate) and PPAR? (rosiglitazone) activators would provide vascular protective benefits similar to full individual doses of these PPAR agonists. Experimental Approach: Male Sprague-Dawley rats infused with Ang II (120?ng?kg?1?min?1) were treated with rosiglitazone (1 or 2?mg?kg?1?day?1) alone or concomitantly with fenofibrate (30?mg?kg?1?day?1) for 7 days. Thereafter, vessels was assessed on a pressurized myograph, while NAD(P)H oxidase activity was determined by lucigenin chemiluminescence. Inflammation was evaluated using ELISA for NF?B and Western blotting for adhesion molecules. Key Results: Ang II-induced blood pressure increase, impaired acetylcholine-induced vasorelaxation, altered vascular structure, and enhanced vascular NAD(P)H oxidase activity and inflammation were significantly reduced by low dose rosiglitazone+fenofibrate. Conclusions and Implications: Combined low doses of PPAR? and PPAR? activators attenuated development of hypertension, corrected vascular structural abnormalities, improved endothelial function, oxidative stress, and vascular inflammation. These agents used in low-dose combination have synergistic vascular protective effects. The clinical effects of combined low-dose PPAR? and PPAR? activators as vascular protective therapy, potentially with reduced side-effects and drug interactions, should be assessed. PMID:17351653

De Ciuceis, C; Amiri, F; Iglarz, M; Cohn, J S; Touyz, R M; Schiffrin, E L

2007-01-01

276

Intra-abdominal hypertension due to heparin - induced retroperitoneal hematoma in patients with ventricle assist devices: report of four cases and review of the literature  

PubMed Central

Introduction Elevated intra-abdominal pressure (IAP) has been identified as a cascade of pathophysiologic changes leading in end-organ failure due to decreasing compliance of the abdomen and the development of abdomen compartment syndrome (ACS). Spontaneous retroperitoneal hematoma (SRH) is a rare clinical entity seen almost exclusively in association with anticoagulation states, coagulopathies and hemodialysis; that may cause ACS among patients in the intensive care unit (ICU) and if treated inappropriately represents a high mortality rate. Case Presentation We report four patients (a 36-year-old Caucasian female, a 59-year-old White-Asian male, a 64-year-old Caucasian female and a 61-year-old Caucasian female) that developed an intra-abdominal hypertension due to heparin-induced retroperitoneal hematomas after implantation of ventricular assist devices because of heart failure. Three of the patients presented with dyspnea at rest, fatigue, pleura effusions in chest XR and increased heart rate although b-blocker therapy. A 36-year old female (the forth patient) presented with sudden, severe shortness of breath at rest, 10 days after an "acute bronchitis". At the time of the event in all cases international normalized ratio (INR) was <3.5 and partial thromboplastin time <65 sec. The patients were treated surgically, the large hematomas were evacuated and the systemic manifestations of the syndrome were reversed. Conclusion Identifying patients in the ICU at risk for developing ACS with constant surveillance can lead to prevention. ACS is the natural progression of pressure-induced end-organ changes and develops if IAP is not recognized and treated in a timely manner. Failure to recognize and appropriately treat ACS is fatal while timely intervention - if indicated - is associated with improvements in organ function and patient survival. Means for surgical decision making are based on clinical indicators of adverse physiology, rather than on a single measured parameter. PMID:21067596

2010-01-01

277

Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries.  

PubMed

Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an important role during hypoxia-induced vascular remodeling and pulmonary hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR) is expressed in rat PASMCs. However, little is known about the role of CaSR in phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying mechanisms. In this study, we investigated whether CaSR induces the proliferation of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of medial wall thickness to the external diameter (WT %), and cross-sectional total vessel wall area to the total area (WA %) of small pulmonary arteries were determined by hematoxylin and eosin (HE), masson trichrome and Weigert's staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9, the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p-ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small pulmonary arteries, including calponin, SM?-actin (SMA?), and osteopontin (OPN), were analyzed by immunohistochemistry and Western blotting, respectively. In addition, immunohistochemistry was applied to paraffin-embedded human tissues from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF). Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were gradually increased with the prolonged hypoxia. At the same time, the expressions of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased, while the expressions of SMA? and calponin were significantly reduced in lung tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR) enhanced but NPS2390 (an antagonist of CaSR) weakened these hypoxic effects. We further found that the expression change of CaSR, PCNA, and SMC phenotypic marker proteins in PAH/CHF lungs was similar to those in PAH rats. Our data suggest that CaSR is involved in the pulmonary vascular remodeling and PAH by promoting phenotypic modulation of small pulmonary arteries. PMID:25063217

Peng, Xue; Li, Hong-Xia; Shao, Hong-Jiang; Li, Guang-Wei; Sun, Jian; Xi, Yu-Hui; Li, Hong-Zhu; Wang, Xin-Yan; Wang, Li-Na; Bai, Shu-Zhi; Zhang, Wei-Hua; Zhang, Li; Yang, Guang-Dong; Wu, Ling-Yun; Wang, Rui; Xu, Chang-Qing

2014-11-01

278

Severe pre-eclampsia and hypertensive crises.  

PubMed

Hypertensive disorders of pregnancy are one of the leading causes of peripartum morbidity and mortality globally. Hypertensive disease in pregnancy is associated with a spectrum of severity, ranging from mild pregnancy-induced hypertension to eclampsia. Although most cases of pre-eclampsia may be managed successfully, severe pre-eclampsia is a life-threatening multisystem disease associated with eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, acute kidney injury, pulmonary oedema, placental abruption and intrauterine foetal death. Management of severe pre-eclampsia includes identification of high-risk patients, optimisation of antenatal care, early intervention and the identification and early management of complications. In the first instance, oral anti-hypertensive agents, including labetalol, nifedipine and methyldopa, should be tried. If oral anti-hypertensive agents have failed to adequately control blood pressure, intravenous anti-hypertensives should be considered. Commonly used intravenous anti-hypertensives include labetalol, hydralazine and glyceryl trinitrate. In addition to anti-hypertensive agents, close attention should be given to regular clinical examination, assessment of fluid balance, neurologic status and monitoring of other vital signs. Magnesium sulphate should be considered early to prevent seizures. Delivery of the baby is the definitive management of severe pre-eclampsia. PMID:23962474

Arulkumaran, N; Lightstone, L

2013-12-01

279

Calcineurin inhibitors and hypertension: a role for pharmacogenetics?  

PubMed

Hypertension is a common side effect of calcineurin inhibitors (CNIs), which are drugs used to prevent rejection after transplantation. Hypertension after kidney transplantation has been associated with earlier graft failure and higher cardiovascular mortality in the recipient. Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension. These insights raise the question whether polymorphisms in the genes encoding these proteins increase the risk of CNI-induced hypertension. Predicting who is at risk for CNI-induced hypertension may be useful for when selecting specific interventions, including dietary salt restriction, thiazide diuretics or a CNI-free immunosuppressive regimen. This review aims to explore the pharmacogenetics of CNI-induced hypertension, highlighting the knowns and unknowns. PMID:25141899

Moes, Arthur D; Hesselink, Dennis A; Zietse, Robert; van Schaik, Ron H N; van Gelder, Teun; Hoorn, Ewout J

2014-06-01

280

Refeeding hypertension in dietary obesity  

SciTech Connect

A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac {beta}-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of ({sup 3}H)dihydroalpranolol; and (2) the decrease in heart rate as a result of {beta}-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension.

Ernsberger, P.; Nelson, D.O. (Northwestern Univ. Medical School, Chicago, IL (USA))

1988-01-01

281

Hypertension in women  

PubMed Central

Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. PMID:25028640

Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

2013-01-01

282

Gestational Hypertension and Preeclampsia  

MedlinePLUS

... to your dashboard . Gestational hypertension and preeclampsia 4:17 Gestational hypertension is high blood pressure that develops ... Show with 1:02 Teen2Teen: Truth and 10:17 How your baby grows: 1:27 Executive Engagement ...

283

Pulmonary hypertension - at home  

MedlinePLUS

Pulmonary hypertension (PAH) is abnormally high blood pressure in the arteries of the lungs. With PAH, the right ... al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology ...

284

Epidemiology of hypertensive kidney disease  

Microsoft Academic Search

The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD) attributable to hypertension continues to rise worldwide. Identifying the precise prevalence of CKD attributable to hypertension is difficult owing to the absence of uniform criteria to establish a diagnosis of hypertensive nephropathy. Despite the increasing prevalence of CKD-associated hypertension, awareness of hypertension among individuals with CKD remains

Suneel Udani; Ivana Lazich; George L. Bakris

2010-01-01

285

Hypertension in developing countries.  

PubMed

The past 2 decades have seen a considerable global increase in cardiovascular disease, with hypertension remaining by far the most common. More than one-third of adults in Africa are hypertensive; as in the urban populations of most developing countries. Being a condition that occurs with relatively few symptoms, hypertension remains underdetected in many countries; especially in developing countries where routine screening at any point of health care is grossly underutilized. Because hypertension is directly related to cardiovascular disease, this has led to hypertension being the leading cause of adverse cardiovascular outcomes, as a result of patients living, often unknowingly, with uncontrolled hypertension for prolonged periods of time. In Africa, hypertension is the leading cause of heart failure; whereas at global levels, hypertension is responsible for more than half of deaths from stroke, just less than half of deaths from coronary artery disease, and for more than one-tenth of all global deaths. In this review, we discuss the escalating occurrence of hypertension in developing countries, before exploring the strengths and weaknesses of different measures to control hypertension, and the challenges of adopting these measures in developing countries. On a broad level, these include steps to curb the ripple effect of urbanization on the health and disease profile of developing societies, and suggestions to improve loopholes in various aspects of health care delivery that affect surveillance and management of hypertension. Furthermore, we consider how the industrial sectors' contributions toward the burden of hypertension can also be the source of the solution. PMID:24786443

Tibazarwa, Kemi B; Damasceno, Albertino A

2014-05-01

286

Economics of hypertension control. World Hypertension League.  

PubMed Central

This paper summarizes the key aspects of the problem of estimating the economic burden of hypertension and hypertension-related disease, the use of economic models, and the opportunities for containing the costs. More information is needed on the population-attributable risk of hypertension in various countries, which is indispensable to estimate the part of hypertension in the burden of stroke and heart disease. The population and high-risk approaches to hypertension control also have economic consequences, which may vary in different societies and must be assessed to ensure proper allocation of resources. Cost-containment can be achieved by more selective diagnostic investigations and by opting for cheaper drugs, though the choice of treatment is difficult owing to uncertainties in the quality-of-life estimates. PMID:7554012

1995-01-01

287

PPAR? binding to heme oxygenase 1 promoter prevents angiotensin II-induced adipocyte dysfunction in Goldblatt hypertensive rats  

PubMed Central

Objective: Renin–angiotensin system (RAS) regulates adipogenic response with adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown the role of peroxisome proliferator-activated receptor-? (PPAR?) agonist in attenuation of angiotensin II-induced oxidative stress. The aim of this study was to explore a potential mechanistic link between PPAR? and the cytoprotective enzyme heme oxygenase-1 (HO-1) and to elucidate the contribution of HO-1 to the adipocyte regulatory effects of PPAR? agonism in an animal model of enhanced RAS, the Goldblatt 2 kidney 1 clip (2K1C) model. Method: We first established a direct stimulatory effect of the PPAR? agonist (GW 501516) on the HO-1 gene by demonstrating increased luciferase activity in COS-7 cells transfected with a luciferase-HO-1 promoter construct. Sprague-Dawley rats were divided into four groups: sham-operated animals, 2K1C rats and 2K1C rats treated with GW 501516, in the absence or presence of the HO activity inhibitor, stannous mesoporphyrin (SnMP). Results: 2K1C animals had increased visceral adiposity, adipocyte hypertrophy, increased inflammatory cytokines, increased circulatory and adipose tisssue levels of renin and Ang II along with increased adipose tissue gp91 phox expression (P<0.05) when compared with sham-operated animals. Treatment with GW 501516 increased adipose tissue HO-1 and adiponectin levels (P<0.01) along with enhancement of Wnt10b and ?-catenin expression. HO-1 induction was accompanied by the decreased expression of Wnt5b, mesoderm specific transcript (mest) and C/EBP? levels and an increased number of small adipocytes (P<0.05). These effects of GW501516 were reversed in 2K1C animals exposed to SnMP (P<0.05). Conclusion: Taken together, our study demonstrates, for the first time, that increased levels of Ang II contribute towards adipose tissue dysregulation, which is abated by PPAR?-mediated upregulation of the heme-HO system. These findings highlight the pivotal role and symbiotic relationship of HO-1, adiponectin and PPAR? in the regulation of metabolic homeostasis in adipose tissues. PMID:23779049

Sodhi, K; Puri, N; Kim, D H; Hinds, T D; Stechschulte, L A; Favero, G; Rodella, L; Shapiro, J I; Jude, D; Abraham, N G

2014-01-01

288

Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses.  

PubMed

The stimulation of pulmonary beta2-adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol-a beta2-adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise-induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications), furosemide (250 mg i.v., 4 h pre-exercise)-control, and furosemide (250 mg i.v., 4 h pre-exercise)+clenbuterol (0.8 microg/kg i.v., 11 min pre-exercise) experiments. The sequence of these treatments was randomized for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, pulmonary vascular pressures were determined at rest, sub-maximal exercise, and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate. In the control study, incremental exercise resulted in progressive significant (P<0.05) increments in heart rate, right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures, and all horses experienced EIPH. Furosemide administration caused a significant (P<0.05) reduction in mean right atrial as well as pulmonary capillary and venous pressures of standing horses. Although exercise in the furosemide-control experiments also caused right atrial and pulmonary vascular pressures to increase significantly (P<0.05), the increment in mean pulmonary capillary and wedge pressures was significantly (P<0.05) attenuated in comparison with the control study, but all horses experienced EIPH. Clenbuterol administration to standing horses premedicated with furosemide caused tachycardia, but significant changes in right atrial or pulmonary vascular pressures were not discerned at rest. During exercise in the furosemide+clenbuterol experiments, heart rate, mean right atrial as well as pulmonary arterial, capillary and wedge pressures increased significantly (P<0.05), but these data were not different from the furosemide-control experiments, and all horses experienced EIPH as well. Thus, it was concluded that clenbuterol administration is ineffective in modifying the pulmonary hemodynamic effects of furosemide in standing or exercising horses. Because the intravascular force exerted onto the blood-gas barrier of horses premedicated with furosemide remained unaffected by clenbuterol administration, it is believed that concomitant clenbuterol administration is unlikely to offer additional benefit to healthy horses experiencing EIPH. PMID:11168917

Manohar, M; Goetz, T E; Rothenbaum, P; Humphrey, S

2000-12-01

289

Superoxide Dismutase Mimetic, MnTE-2-PyP, Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension, Pulmonary Vascular Remodeling, and Activation of the NALP3 Inflammasome  

PubMed Central

Abstract Aims: Pulmonary hypertension (PH) is characterized by an oxidant/antioxidant imbalance that promotes abnormal vascular responses. Reactive oxygen species, such as superoxide (O2•?), contribute to the pathogenesis of PH and vascular responses, including vascular remodeling and inflammation. This study sought to investigate the protective role of a pharmacological catalytic antioxidant, a superoxide dismutase (SOD) mimetic (MnTE-2-PyP), in hypoxia-induced PH, vascular remodeling, and NALP3 (NACHT, LRR, and PYD domain-containing protein 3)–mediated inflammation. Results: Mice (C57/BL6) were exposed to hypobaric hypoxic conditions, while subcutaneous injections of MnTE-2-PyP (5?mg/kg) or phosphate-buffered saline (PBS) were given 3× weekly for up to 35 days. SOD mimetic-treated groups demonstrated protection against increased right ventricular systolic pressure, indirect measurements of pulmonary artery pressure, and RV hypertrophy. Vascular remodeling was assessed by Ki67 staining to detect vascular cell proliferation, ?-smooth muscle actin staining to analyze small vessel muscularization, and hyaluronan (HA) measurements to assess extracellular matrix modulation. Activation of the NALP3 inflammasome pathway was measured by NALP3 expression, caspase-1 activation, and interleukin 1-beta (IL-1?) and IL-18 production. Hypoxic exposure increased PH, vascular remodeling, and NALP3 inflammasome activation in PBS-treated mice, while mice treated with MnTE-2-PyP showed an attenuation in each of these endpoints. Innovation: This study is the first to demonstrate activation of the NALP3 inflammasome with cleavage of caspase-1 and release of active IL-1 ? and IL-18 in chronic hypoxic PH, as well as its attenuation by the SOD mimetic, MnTE-2-PyP. Conclusion: The ability of the SOD mimetic to scavenge extracellular O2•? supports our previous observations in EC-SOD-overexpressing mice that implicate extracellular oxidant/antioxidant imbalance in hypoxic PH and implicates its role in hypoxia-induced inflammation. Antioxid. Redox Signal. 18, 1753–1764. PMID:23240585

Villegas, Leah R.; Kluck, Dylan; Field, Carlie; Oberley-Deegan, Rebecca E.; Woods, Crystal; Yeager, Michael E.; El Kasmi, Karim C.; Savani, Rashmin C.; Bowler, Russell P.

2013-01-01

290

Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?  

PubMed Central

Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM <220g  and athletes with LVM >220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue. PMID:25132960

Leischik, Roman; Spelsberg, Norman; Niggemann, Hiltrud; Dworrak, Birgit; Tiroch, Klaus

2014-01-01

291

The Effect of Acetyl Salicylic Acid Induced Nitric Oxide Synthesis in the Normalization of Hypertension through the Stimulation of Renal Cortexin Synthesis and by the Inhibition of Dermcidin Isoform 2, A Hypertensive Protein Production  

PubMed Central

Currently, there is no specific medication for essential hypertension (EH), a major form of the condition, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit dermcidin isoform 2 (dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man. PMID:25324696

Ghosh, Rajeshwary; Bank, Sarbashri; Maji, Uttam K.; Bhattacharya, Rabindra; Guha, Santanu; Khan, Nighat N.; Sinha, A. Kumar

2014-01-01

292

Vascular relaxation and cyclic guanosine monophosphate in hypertension  

SciTech Connect

Isolated aortae from hypertensive rats have a decreased relaxation response to acetylcholine (Ach), A23187, and nitroprusside (SNP). Since cyclic guanosine monophosphate (cGMP) has been shown to increase in response to these vasodilators, the authors measured cGMP in response to these agents in isolated aortae from normotensive rats and DOCA, 1K1C, and coarctation induced hypertension. cGMP was measured by radioimmunoassay in vessels after exposure to phenylephrine followed by either Ach, A23187, or SNP. The aortae from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to Ach and A23187. Rises in cGMP in response to SNP were also attenuated in aortae from the hypertensive rats, even at concentrations which induced similar relaxation in normotensive and hypertensive blood vessels. The data suggest that changes in cGMP do not necessarily reflect changes in endothelium independent vascular relaxation in hypertension.

Otsuka, Y.; DiPiero, A.; Lockette, W.

1986-03-01

293

Quantitative left ventricular contractility analysis under stress: a new practical approach in follow-up of hypertensive patients  

Microsoft Academic Search

Excessive sympathetic activity and stress-induced left ventricular (LV) hypercontractility have been described in hypertensive LV hypertrophy. Recent quantitative data have shown that hypertensive LV hypertrophy is associated with preserved global LV function. However, progression of uncontrolled hypertension have detrimental effects on both the ejection fraction (EF) and LV contractile response to stress. Hypertensive LV hypertrophy has some common characteristics, including

F Yalçin; H Yalçin; N Küçükler; T P Abraham

2011-01-01

294

The role of chemokines in hypertension.  

PubMed

Hypertension is a major risk factor for cardiovascular disease, which is a serious health problem in the highly industrialized countries. In more than 95% of the cases, the etiology of hypertension remains unknown. A key role in the etiology of hypertension is played by endothelial dysfunction and the inflammatory reaction in the vascular wall, in which the low molecular weight proteins so called chemokines are involved. The chemokines involved in the pathogenesis of hypertension include monocyte chemoattractant protein-1, MCP-1, CCL2, interferon-inducible protein (IP-10; CXCL10), interleukin-8 (IL-8; CXCL8), RANTES (CCL5), fractalkine (CX3CL1) and their receptors CCR2, CCR5, CXCR1, CXCR2, CXCR3 and CX3CR1. The mechanisms involving chemokines and their receptors in the pathogenesis of hypertension are complex and not fully understood. They include the impact of the migration of macrophages and monocytes to the vascular wall, endothelial dysfunction, effects on nitric oxide and endothelin-1 and smooth muscle cell proliferation. Chemokines are also involved in the pathogenesis of complications of hypertension, such as atherosclerosis, myocardial and renal fibrosis. In Poland, only about 26% of patients are effectively treated with antihypertensive drugs. The use of new therapeutic methods based on the inhibition of the inflammatory process in the vascular wall, including the impact on the function of chemokines and their receptors, could improve the effectiveness of the treatment of hypertension. PMID:24979502

Martynowicz, Helena; Janus, Agnieszka; Nowacki, Dorian; Mazur, Grzegorz

2014-01-01

295

Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury  

PubMed Central

Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension. PMID:25295006

Hye Khan, Md. Abdul; Falck, John R.; Manthati, Vijaya L.; Campbell, William B.; Imig, John D.

2014-01-01

296

[Genetic markers of hypertension].  

PubMed

Essential hypertension is a widespread multifactorial pathology which is probably controlled by numerous genes. Twenty to forty percent of hypertension may be genetically determined. In this review, polymorphism of three group of candidate genes is analyzed. Products of these genes are most likely involved in hypertension development. These are the genes controlling the renin-angiotensin system, ionic channels, and nitric oxide system and NO-synthase. PMID:10495944

Chistiakov, D A; Turakulov, R I

1999-05-01

297

Nutrition therapy for hypertension  

Microsoft Academic Search

A contemporary approach to hypertension and prevention are covered in this article. It contains important information for\\u000a clinicians, such as hypertension management, metabolic syndrome issues, lifestyle behavioral management, nutrient issues,\\u000a weight loss treatments (ie, medications and surgical procedures) the role of physical activity, and pharmacologic treatment. The Dietary Approaches\\u000a to Stop Hypertension (DASH) trial eating plan is discussed at length,

Elise Zimmerman; Judith Wylie-Rosett

2003-01-01

298

Alcohol consumption and hypertension  

Microsoft Academic Search

Hypertension is a major independent risk factor for cardiovascular disease. In alcohol-consuming populations, the amount of\\u000a alcohol consumption has significant impact on blood pressure values, the prevalence of hypertension, and cardiovascular as\\u000a well as all-cause mortality. In this review, we focus on the connection between alcohol consumption and hypertension, and\\u000a discuss the consequences on cardiovascular risk.

Michael Huntgeburth; Henrik ten Freyhaus; Stephan Rosenkranz

2005-01-01

299

Quantitative estimate of pinocytosis in experimental acute hypertension  

Microsoft Academic Search

Cerebral cortical arterioles in focal neocortical areas develop increased permeability to plasma proteins and protein tracers in experimental hypertensive encephalopathy. The mechanism underlying this increased permeability has been the subject of several studies. In our previous studies of angiotensin-induced acute hypertension, pinocytosis appeared to be the pricipal mechanism for the increased blood-brain barrier (BBB) permeability observed. In the present study

S. Nag; D. M. Robertson; H. B. Dinsdale

1979-01-01

300

Cardiopulmonary Responses of Wistar Kyoto, Spontaneously Hypertensive, and Stroke-prone Spontaneously Hypertensive Rats to Particulate Matter (PM) Exposure  

Microsoft Academic Search

Humans with underlying cardiovascular disease, including stroke, are more susceptible to ambient particulate matter (PM)-induced morbidity and mortality. We hypothesized that stroke-prone spontaneously hypertensive rats (SHRSP) would be more susceptible than healthy Wistar Kyoto (WKY) rats to PM-induced cardiac oxidative stress and pulmonary injury. We further postulated that PM-induced injury would be greater in SHRSP than in spontaneously hypertensive rats

J. Grace Wallenborn; Mette C. Schladweiler; Abraham Nyska; Jo Anne Johnson; Ronald Thomas; Richard H. Jaskot; Judy H. Richards; Allen D. Ledbetter; Urmila P. Kodavanti

2007-01-01

301

Pediatric endocrine hypertension  

PubMed Central

Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140

Bhavani, Nisha

2011-01-01

302

[Hungarian Hypertension Registry].  

PubMed

Today, hypertension is considered endemic throughout the world. The number of individuals with high blood pressure and the increasing risk, morbidity and mortality caused by hypertension despite modern therapy do not decrease sufficiently. Hypertension has become a public health issue. Prevention and effective care require integrated datasets about many features, clinical presentation and therapy of patients with hypertension. The lack of this database in Hungary prompted the development of the registry which could help to provide population-based data for analysis. Data collection and processing was initiated by the Hungarian Society of Hypertension in 2002. Data recording into the Hungarian Hypertension Registry was performed four times (2002, 2005, 2007, 2011) and the registry currently contains data obtained from 108,473 patients. Analysis of these data indicates that 80% of the patients belong to the high or very high cardiovascular risk group. The registry provides data on cardiovascular risk of the hypertensive populations and the effectiveness of antihypertensive therapy in Hungary. Based on international experience and preliminary analysis of data from the Hungarian Hypertension Registry, establishment of hypertension registry may support the effectiveness of public health programs. A further step would be needed for proper data management control and the application of professional principles of evidence-based guidelines in the everyday practice. PMID:24796784

Kiss, István; Kékes, Ede

2014-05-11

303

Pathogenesis of Hypertension  

NSDL National Science Digital Library

Physiology in Medicine review article A clearer understanding of the pathogenesis of hypertension will probably lead to more highly targeted therapies and to greater reduction in hypertension-related cardiovascular disease morbidity than can be achieved with current empirical treatment. Hypertension clusters in families and results from a complex interaction of genetic and environmental factors. Endothelial dysfunction, increased vascular reactivity, and vascular remodeling may be causes, rather than consequences, of blood pressure elevation; increased vascular stiffness contributes to isolated systolic hypertension in the elderly.

MD Suzanne Oparil (University of Alabama at Birmingham Department of Medicine); MD M. Amin Zaman (University of Alabama at Birmingham Dept. of Medicine, Division of Cardiovascular Diseases); MD David A Calhoun (University of Alabama at Birmingham Dept. of Medicine, Division of Cardiovascular Disease)

2003-11-04

304

Renal Pathology: SC23-3 HYPERTENSION-ASSOCIATED VASCULAR DISEASE.  

PubMed

Hypertensive-associated vascular disease of the kidneys or hypertensive nephrosclerosis, rather than implying a linear direct relationship to renal damage induced by hypertension, may indicate complex environmental and genetic factors, which together promote the coexistence of renal lesion and hypertension in this clinical setting. We discuss morphologic findings of hypertension-associated vascular disease of the kidneys. We also discuss possible pathogenetic factors including hypertension, ethnicity, aberrant autoregulation, prothrombotic mechanisms, low birth weight, decreased nephron number, genetic factors, dysmetabolic syndrome, and macrophage polarization. PMID:25188166

Paueksakon, Paisit

2014-10-01

305

Ginkgo biloba extract attenuates the development of hypertension in deoxycorticosterone acetate-salt hypertensive rats.  

PubMed

1. We examined the effects of Ginkgo biloba extract (GBE) on the development of hypertension, platelet activation and renal dysfunction in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Both DOCA-salt hypertensive rats and normotensive rats were fed a 2% GBE diet for 20 days. Blood pressure (BP) was measured by two methods, namely by the tail-cuff and telemetry methods. 2. Development of hypertension was attenuated in rats fed a 2% GBE diet. In addition, an increase in heart weight, an indicator of sustained high BP, was inhibited significantly by feeding of the GBE diet. 3. Decreases in 5-hydroxytryptamine content in platelets, a marker of platelet activation in vivo associated with hypertension, were also prevented by feeding of the GBE diet. Ginkgo biloba extract itself did not inhibit ADP- and collagen-induced platelet aggregation examined in vitro. Feeding of the GBE diet tended to inhibit increases in plasma urea nitrogen due to hypertension. 4. The telemetry study demonstrated that BP and heart rate (HR) showed a clear circadian rhythm and the antihypertensive effect of GBE was prominent in the daytime, a resting period for rats. This anti-hypertensive effect of GBE was not detected in normotensive rats. In contrast, the inhibitory effect of GBE on HR was independent of time and was observed in both normotensive and hypertensive rats. 5. These results indicate that GBE has an anti-hypertensive and bradycardiac action, which are time dependent and independent, respectively. Thus, it appears that the chronopharmacological action of GBE may be ascribed not to pharmacokinetic factors, but rather to a circadian susceptibility rhythm to GBE in DOCA-salt hypertensive rats. PMID:10779125

Umegaki, K; Shinozuka, K; Watarai, K; Takenaka, H; Yoshimura, M; Daohua, P; Esashi, T

2000-04-01

306

Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain  

Microsoft Academic Search

Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present study describes ultrastructural alterations of the cerebrocortical capillary wall, such as thickening and collagen

Eszter Farkas; Gineke I. De Jong; Etelka Apró; Jeanine I. H. Keuker; Paul G. M. Luiten

2001-01-01

307

Exercise Intolerance in Rats With Hypertensive Heart Disease Is Associated With Impaired Diastolic Relaxation  

Microsoft Academic Search

A decrease in functional capacity is one of the most important clinical manifestations of hypertensive heart disease, but its cause is poorly understood. Our purpose was to evaluate potential causes of hypertension-induced exercise intolerance, focusing on identifying the type(s) of cardiac dysfunction associated with the first signs of exercise intolerance during the course of hypertensive heart disease. Exercise capacity was

Marco Guazzi; Daniel A. Brenner; Carl S. Apstein; Kurt W. Saupe

308

Tumor necrosis factor ?: A major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats  

Microsoft Academic Search

Background\\/Aims: Portal hypertension is often accompanied by a hyperdynamic circulatory syndrome. Tumor necrosis factor (TNF) ? causes vasodilatation and a hyperdynamic state in mammals by activating nitric oxide synthesis. The aim of this study was to investigate whether TNF-? plays a role in developing the hyperdynamic syndrome in portal hypertension. Methods: Portal-hypertensive rats, induced by partial ligation of the portal

Juan Carlos Lopez-Talavera; William W. Merrill; Roberto J. Groszmann

1995-01-01

309

Refeeding hypertension in dietary obesity  

PubMed Central

A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state (125 ± 8 vs. 121 ± 4 mmHg in chow-fed controls) or mean arterial pressure under urethan anesthesia (71 ± 4 vs. 63 ± 3 mmHg). In contrast, mild hypertension developed in intermittantly fasted obese animals (a 21-mmHg increase in systolic blood pressures measured in the conscious state and a 16-mmHg increase in mean arterial pressure under anesthesia relative to chow-fed controls). The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure (12 ± 2 mmHg at 2 days) accompanied the onset of supplemented fasting and was maintained thereafter (2.7 ± 2.6 mmHg further decrease during the latter half of the fast). With refeeding, blood pressure rose precipitously (13 ± 3 mmHg in the 1st 2 days), despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period (5.2 ± 2.8 mmHg). After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Despite normophagia, intermittently fasted rats gained 30% more weight and had 96% heavier retroperitoneal fat pads. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since 1) cardiac ?-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of [3H]dihydroalpranolol; and 2) the decrease in heart rate as a result of ?-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension. PMID:3337269

ERNSBERGER, PAUL; NELSON, DOUGLAS O.

2010-01-01

310

Opiate receptors and the endorphin-mediated cardiovascular effects of clonidine in rats: evidence for hypertension-induced mu-subtype to delta-subtype changes.  

PubMed Central

Effects of opiate receptor antagonists on centrally mediated cardiovascular responses to clonidine and beta-endorphin were studied in urethane-anesthetized spontaneously hypertensive Okamoto-Aoki rats (SHR), normotensive Sprague-Dawley rats, and Sprague-Dawley rats made hypertensive with deoxycorticosterone pivalate/salt. Microinjection of 270 pmol of naloxone into the nucleus tractus solitarii (NTS) significantly inhibited the hypotensive and bradycardic response to 5 nmol of similarly administered clonidine in both SHR and normotensive Sprague-Dawley rats. In SHR, a similar inhibition was observed after the delta-opiate receptor antagonist ICI 174864, but not after the mu-receptor antagonist beta-funaltrexamine (both at 270 pmol, intra-NTS), whereas in normotensive Sprague-Dawley rats, beta-funaltrexamine, but not ICI 174864, was an effective inhibitor. The same pattern of differential inhibition was seen when clonidine was given i.v. and the opiate antagonists were given intracisternally in SHR and Sprague-Dawley rats. Intra-NTS microinjection of 280 fmol of beta-endorphin caused hypotension and bradycardia, and these effects were similarly inhibited by ICI 174864 in SHR and by beta-funaltrexamine in Sprague-Dawley rats. In Sprague-Dawley rats made hypertensive by chronic administration of deoxycorticosterone pivalate and salt, the hypotensive and bradycardic effects of intra-NTS clonidine were inhibited by ICI 174864, but not by beta-funaltrexamine, a pattern similar to that in SHR, but different from that in normotensive Sprague-Dawley rats. These results support the hypothesis that beta-endorphin release and subsequent stimulation of opiate receptors in the NTS are involved in the cardiovascular effects of clonidine in rats. These results further suggest, however, that hypertension regulates the subtype of opiate receptors mediating these effects. PMID:2825200

Mosqueda-Garcia, R; Kunos, G

1987-01-01

311

[Arterial hypertension and salt intake].  

PubMed

More than 25% of adult population worldwide and according to the EHUH study 37% of the adult population of Croatia have hypertension. In the last decades, a dramatic increase has been recorded in the prevalence of hypertension, and it is predicted that this trend will lead to an even higher prevalence in the near future. This could primarily be explained by strong influence of environmental factors. Many epidemiological and interventional studies have proved that high salt intake is one of the most important risk factors. High salt intake increases total peripheral vascular resistance, induces oxidative stress and inflammation, thus accelerating the atherosclerotic process. Independently of the effects on blood pressure, salt intake promotes left ventricular hypertrophy and microalbuminuria and increases the risk of stroke. Interventional studies have shown that salt intake reduction is associated with lower blood pressure and lower cardiovascular morbidity and mortality. Reducing salt intake in daily meals should be the main measure in primary prevention of cardiovascular and renal diseases, and it should be repeatedly emphasized not only to hypertensive patients, but also to the population at large. PMID:20649075

Jelakovi?, Bojan; Vukovi?, Ivana; Reiner, Zeljko

2010-05-01

312

Obesity and hypertension  

Microsoft Academic Search

Substantial evidence from epidemiological data supports a link between obesity and hypertension. However, the relationship between the two disorders is not straightforward and most likely represents an interaction of demographic, genetic, hormonal, renal, and hemodynamic factors. Age, race, and sex also modulate the strength of the association between obesity and hypertension. Hyperinsulinemia, which is characteristic of obesity, can contribute to

Nasser Mikhail; Michael S. Golub; Michael L. Tuck

1999-01-01

313

Bothrops jararaca Peptide with AntiHypertensive Action Normalizes Endothelium Dysfunction Involved in Physiopathology of Preeclampsia  

Microsoft Academic Search

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, is a major cause of fetal and maternal morbidity and mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide isolated from Bothrops jararaca venom, has been attributed with potent anti-hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti-hypertensive actions involved NO production in spontaneous hypertensive rats. Using in vitro studies

Gabriel Benedetti; Katia L. P. Morais; Juliano R. Guerreiro; Eduardo Fontana de Oliveira; Mara Sandra Hoshida; Leandro Oliveira; Nelson Sass; Ivo Lebrun; Henning Ulrich; Claudiana Lameu; Antonio Carlos Martins de Camargo

2011-01-01

314

Hypertension in the Elderly  

PubMed Central

Background. The incidence of hypertension in the Western countries is continuously increasing in the elderly population and remains the leading cause of cardiovascular and morbidity. Methods. we analysed some significant clinical trials in order to present the relevant findings on those hypertensive population. Results. Several studies (SYST-EUR, HYVET, CONVINCE, VALUE, etc.) have demonstrated the benefits of treatment (nitrendipine, hydrochrotiazyde, perindopril, indapamide, verapamil, or valsartan) in aged hypertensive patients not only concerning blood pressure values but also the other important risk factors. Conclusion. Hypertension is the most prevalent cardiovascular disorder in the Western countries, and the relevance of receiving pharmacological treatment of hypertension in aged patients is crucial; in addition, the results suggest that combination therapy—nitrendipine plus enalapril—could have more benefits than those observed with the use of nitrendipine alone. PMID:21876789

Gil-Extremera, Blas; Cia-Gomez, Pedro

2012-01-01

315

Hypertension in pregnancy.  

PubMed

Hypertensive disorders of pregnancy represent the second commonest cause of direct maternal death and complicate an estimated 5-10 % of pregnancies. Classification systems aim to separate hypertension similar to that seen outside pregnancy (chronic and gestational hypertension) from the potentially fatal pregnancy-specific conditions. Preeclampsia, HELLP syndrome, and eclampsia represent increasing severities of this disease spectrum. The American College of Obstetricians and Gynecologists' 2013 guidelines no longer require proteinuria as a diagnostic criterion, because of its variable appearance in the disease spectrum. The cause involves inadequate cytotrophoblastic invasion of the myometrium, resulting in placental hypoperfusion and diffuse maternal endothelial dysfunction. Changes in angiogenic and antiangiogentic peptide profiles precede the onset of clinical preeclampsia. Women with preeclampsia should be closely monitored and receive magnesium sulfate intravenously if severe features, HELLP syndrome, or eclampsia occur. Definitive therapy is delivery of the fetus. Hypertension in pregnancy increases future maternal risk of hypertension and cardiovascular disorders. PMID:24477794

Vest, Amanda R; Cho, Leslie S

2014-03-01

316

Influence of anti-hypertensive drug treatment on vascular reactivity in spontaneously hypertensive rats.  

PubMed Central

1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A comparison of the vascular reactivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) was also made in isolated perfused mesenteric artery preparations from treated and control SH- and Sprague-Dawley rats. 2. Chronic treatment from age 4 to 16 weeks with hydrallazine alone, or a combination of hydrallazine/hydrochlorothiazide/reserpine, ad libitum in the drinking water, prevented the development of hypertension in SH-rats and also reduced the vascular reactivity to NA and 5-HT in isolated vessel preparations from treated compared to control rats. 3. Similar drug treatments started in early established hypertension reduced blood pressure in SH-rats over the 12 week treatment period (from age 8 to 20 weeks) without affecting vascular reactivity to NA and 5-HT in the isolated vessel preparation. 4. Drug treatments had little effect on blood pressure of age-matched Sprague-Dawley rats and no effect on vascular reactivity to NA and 5-HT in the isolated perfused mesenteric artery preparation from treated compared to control rats. 5. These results indicate that the development of increased vascular reactivity and of hypertension in SH-rats occurs simultaneously and, therefore, the vascular changes may be a consequence of the structural changes induced by the raised blood pressure. 6. In established hypertension, no regression of vascular changes was observed despite prolonged reduction of blood pressure. The role of an increased vascular reactivity in the maintenance of hypertension is therefore questionable. PMID:1174760

Hamilton, T C

1975-01-01

317

Perioperative hypertension management  

PubMed Central

Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911

Varon, Joseph; Marik, Paul E

2008-01-01

318

Valsartan regulates myocardial autophagy and mitochondrial turnover in experimental hypertension.  

PubMed

Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The angiotensin II receptor blocker, valsartan, lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with valsartan (320 mg/d) or conventional triple therapy (reserpine+hydralazine+hydrochlorothiazide) for 4 weeks after 6 weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function, and myocardial oxygenation and microcirculation were assessed by multidetector computer tomography, blood oxygen level-dependent MRI, and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner. PMID:24752430

Zhang, Xin; Li, Zi-Lun; Crane, John A; Jordan, Kyra L; Pawar, Aditya S; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O

2014-07-01

319

Responses of mean arterial pressure to pressor agents and diuretics in renal hypertensive and salt hypertensive rats  

PubMed Central

1. The responses of the mean arterial pressure to (—)-noradrenaline, tyramine, angiotensin II-val5-amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone. 2. Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals. 3. Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade. 4. Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade. 5. Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension. 6. Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension. PMID:4326321

Nicholas, T. E.

1971-01-01

320

Clinical Manifestations of Portal Hypertension  

PubMed Central

The portal hypertension is responsible for many of the manifestations of liver cirrhosis. Some of these complications are the direct consequences of portal hypertension, such as gastrointestinal bleeding from ruptured gastroesophageal varices and from portal hypertensive gastropathy and colopathy, ascites and hepatorenal syndrome, and hypersplenism. In other complications, portal hypertension plays a key role, although it is not the only pathophysiological factor in their development. These include spontaneous bacterial peritonitis, hepatic encephalopathy, cirrhotic cardiomyopathy, hepatopulmonary syndrome, and portopulmonary hypertension. PMID:23024865

Al-Busafi, Said A.; McNabb-Baltar, Julia; Farag, Amanda; Hilzenrat, Nir

2012-01-01

321

Pulmonary hypertension and chronic mountain sickness.  

PubMed

Chronic mountain sickness is a syndrome of severe symptomatic polycythemia and hypoxemia occurring in natives or long-term high altitude sojourners. The condition may be complicated by pulmonary hypertension in proportion to decreased oxygenation, indicating hypoxic vasoconstriction and remodeling. Exercise in these patients is associated with a steep slope of pulmonary artery pressure-flow relationships and decreased vascular distensibility. Correction of pulmonary vascular resistance for increased hematocrit decreases the severity of pulmonary hypertension. Exercise-induced pulmonary hypertension in chronic mountain sickness does not affect exercise capacity, in relation to high oxygen content of the blood and increased lung diffusing capacity. Right ventricular failure seems to be an uncommon complication of chronic mountain sickness, but the exact prevalence of the condition is not known. Acetazolamide given for 6 months to patients with chronic mountain sickness improves oxygenation, polycythemia, and pulmonary artery pressure. PMID:23795731

Naeije, Robert; Vanderpool, Rebecca

2013-06-01

322

High Blood Pressure (Hypertension)  

MedlinePLUS

... Women and Diabetes Heart Health for Women High Blood Pressure (Hypertension) Print and Share (PDF 109 KB) ... very sick or even die. What does high blood pressure do to your body? High blood pressure ...

323

Hypertension and Spina Bifida  

MedlinePLUS

... smoking. What are the risk factors for hypertension? Family history; Obesity; High salt intake; Sleep apnea; High stress; Excessive alcohol consumption; Smoking; High cholesterol and triglycerides. All of these ...

324

Hypertensive heart disease  

MedlinePLUS

... failure: pathophysiology and diagnosis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

325

Pregnancy and Portal Hypertension  

Microsoft Academic Search

Pregnancy is a normal physiological state characterized by numerous hemodynamic changes. These hemodynamic changes, although\\u000a necessary for a normal pregnancy, pose a special problem in the presence of portal hypertension. In North America, cirrhosis\\u000a of the liver is the most common cause of portal hypertension. Although rare, the occurrence of pregnancy is not altogether\\u000a unknown in this population. This is

Bimaljit Sandhu; Arun J. Sanyal

326

Orthostatic hypertension. Pathogenetic studies.  

PubMed

Among 1800 referred hypertensive patients, 181 had recumbent diastolic blood pressures (DBP) below 90 mm Hg and standing DBP above 90 mm Hg. Orthostatic increments in DBP were greater in these orthostatic hypertensive patients than in 181 persistently hypertensive patients and 134 normotensive subjects. In 12 patients with orthostatic hypertension, the orthostatic fall in cardiac output (27.3 +/- 2.9%, measured by a respiratory method) was double that in 8 normotensive subjects (13.3 +/- 3.7%, p less than 0.01). An inflated pressure suit over the pelvis and lower limbs prevented the excessive fall in cardiac output and significantly reduced (p less than 0.02) the excessive rise in standing DBP in orthostatic hypertensive patients. Gravitational pooling of blood in the legs and reduction of blood in the head was measured by external gamma counting of autologous erythrocytes labeled with sodium pertechnetate Tc 99m through ports in fixed positions over the leg and the temple. Orthostatic intravascular pooling was significantly greater (p less than 0.01) in orthostatic hypertensive subjects than in normotensive subjects, and the magnitudes of orthostatic pooling and orthostatic increases in DBP were closely correlated (r = +0.85). Plasma norepinephrine concentrations were similar in recumbency and after sustained handgrip exercise, but significantly greater (p less than 0.01) after 5 to 60 mins of standing in orthostatic hypertensive subjects than in normotensive subjects. Our results indicate that orthostatic hypertension is common and that its mechanism in representative patients involves excessive orthostatic blood pooling, which results in decreased venous return, decreased cardiac output, increased sympathetic stimulation (presumably through low-pressure cardiopulmonary receptors), and excessive arteriolar, but not venular, constriction. PMID:3980066

Streeten, D H; Auchincloss, J H; Anderson, G H; Richardson, R L; Thomas, F D; Miller, J W

1985-01-01

327

Pharmacotherapy of Pulmonary Hypertension  

PubMed Central

Pulmonary arterial hypertension is a serious disease with significant morbidity and mortality. While it can occur idiopathically, it is more commonly associated with other cardiac or lung diseases. While most of the available therapies were tested in adult populations, and most therapies in children remain off-label, new reports and randomized trials are emerging that inform the treatment of pediatric populations. This review discusses currently available therapies for pediatric pulmonary hypertension, their biologic rationales, and evidence for their clinical effectiveness. PMID:23036248

Steinhorn, Robin H.

2012-01-01

328

Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats  

SciTech Connect

Researchers have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure.

Sankar, R.; Domer, F.R.; Taylor, B.

1982-09-01

329

Reactive oxygen species scavengers improve voltage-gated K+ channel function in pulmonary arteries of newborn pigs with progressive hypoxia-induced pulmonary hypertension  

PubMed Central

Abstract Changes in voltage-gated K+ (Kv) channel function contribute to the pathogenesis of pulmonary hypertension. Yet the mechanisms underlying Kv channel impairments in the pulmonary circulation remain unclear. We tested the hypothesis that reactive oxygen species (ROSs) contribute to the Kv channel dysfunction that develops in resistance-level pulmonary arteries (PRAs) of piglets exposed to chronic in vivo hypoxia. Piglets were raised in either room air (control) or hypoxia for 3 or 10 days. To evaluate Kv channel function, responses to the Kv channel antagonist 4-aminopyridine (4-AP) were measured in cannulated PRAs. To assess the influence of ROSs, PRAs were treated with the ROS-removing agent M40403 (which dismutates superoxide to hydrogen peroxide), plus polyethylene glycol catalase (which converts hydrogen peroxide to water). Responses to 4-AP were diminished in PRAs from both groups of hypoxic piglets. ROS-removing agents had no impact on 4-AP responses in PRAs from piglets exposed to 3 days of hypoxia but significantly increased the response to 4-AP in PRAs from piglets exposed to 10 days of hypoxia. Kv channel function is impaired in PRAs of piglets exposed to 3 or 10 days of in vivo hypoxia. ROSs contribute to Kv channel dysfunction in PRAs from piglets exposed to hypoxia for 10 days but are not involved with the Kv channel dysfunction that develops within 3 days of exposure to hypoxia. Therapies to remove ROSs might improve Kv channel function and thereby ameliorate the progression, but not the onset, of pulmonary hypertension in chronically hypoxic newborn piglets. PMID:24618540

Aschner, Judy L.

2013-01-01

330

Protective actions of nebivolol on chronic nitric oxide synthase inhibition-induced hypertension and chronic kidney disease in the rat: a comparison with angiotensin II receptor blockade  

PubMed Central

Background. Nitric oxide (NO) deficiency contributes to chronic kidney disease (CKD) progression and hypertension. The ?-blocker, nebivolol (N), also enhances NO production, and we studied whether N attenuates CKD and hypertension caused by chronic NO synthase inhibition (CNOSI). Methods. Male Sprague–Dawley rats on 6 weeks of CNOSI (L-NAME, 150 mg/L drinking water) received placebo (P), N (10 mg/kg/day), olmesartan (O, 2.5 mg/kg/day) or N + O. Blood pressure (BP) and urine protein and NOx (metabolites of NO) were monitored throughout. We measured glomerular sclerosis (GS), creatinine clearance (CCr) and components of the NO and oxidant pathways in the renal cortex. Results. BP increased >50 mmHg in P by weeks 4–6, but no change occurred in N, O or N + O. P rats developed proteinuria and GS and CCr was ?30% of normal. In N, O and N + O, all values remained normal. In renal cortex of P, p22phox and nitrotyrosine abundance as well as H2O2 levels were higher and extracellular superoxide dismutase (EC SOD) was lower versus normal kidneys. N, O and N + O normalized p22phox, H2O2 and EC SOD and increased Mn SOD above normal. The cortical neuronal NO synthase (nNOS) ? abundance increased in P and this was prevented by N, O and N + O. Conclusion. We suggest that the major benefit from both N and O is reduction in oxidative stress in the renal cortex, which may potentiate residual local NO. There was no additive benefit of N + O since each drug effectively prevented injury, but a combination may be beneficial where protection is incomplete with each drug. The increased nNOS? protein seen early in the course of the CKD may contribute to the evolving GS. PMID:21856762

Tsarova, Tatsiana; Sasser, Jennifer M.; Baylis, Chris

2012-01-01

331

Heart rate variability in rats with chronic hypoxic pulmonary hypertension  

Microsoft Academic Search

The precise role of pulmonary hypertension as a possible factor inducing a decrease in heart rate variability is poorly known. Spectral analysis of heart rate variability (HRV) was carried out in 21 Wistar rats before and after exposure to normoxia (N=10) or to 3 weeks of hypobaric hypoxia inducing chronic pulmonary hypertension and right ventricular hypertrophy (N=11). Continuous ECG was recorded

L. Fauchier; A. Melin; V. Eder; D. Antier; P. Bonnet

2006-01-01

332

Superoxide dismustase mimetic tempol decreases blood pressure by increasing renal medullary blood flow in hyperinsulinemic-hypertensive rats  

Microsoft Academic Search

Insulin resistance and compensatory hyperinsulinemia often coexist in hypertensive patients, which may play a role in the development of hypertension. Because medullary blood flow (MBF), which is strongly influenced by the nitric oxide (NO) system, is thought to be an important component of blood pressure and sodium balance, we focused particularly on MBF in fructose-induced hypertensive rats. Moreover, it has

Shizuka Onuma; Kazushige Nakanishi

2004-01-01

333

Effect of blood pressure and physical activity on carotid artery intima–media thickness in stage 1 hypertensives and controls  

Microsoft Academic Search

The aim of the study was to investigate whether hypertension and physical training induce parallel changes in the arterial wall. Ninety-seven never-treated stage 1 hypertensive patients (HT) (systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg) aged 18 to 45 years taking part in the Hypertension and Ambulatory Recording Venetia Study and

Edoardo Casiglia; Paolo Palatini; Santina Da Ros; Valeria Pagliara; Massimo Puato; Francesca Dorigatti; Paolo Pauletto

2000-01-01

334

Adaptation, allometry, and hypertension.  

PubMed

Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure. PMID:8039837

Weder, A B; Schork, N J

1994-08-01

335

Angiotensin II-related hypertension and eye diseases  

PubMed Central

Systemic vascular disease, especially hypertension, has been suspected as a risk factor for some eye diseases including, diabetic retinopathy and age-related macular degeneration. Hypertension can contribute to chronic diseases by hemodynamic injury and/or cellular actions induced by hypertension-related hormones or growth factors. Among the most important is Angiotensin II (Ang II), which controls blood pressure and induces different cellular functions that may be dependent or independent of its effect on blood pressure. Importantly, as is true for heart, kidney and other organs, the renin-angiotensin system (RAS) is present in the eye. So, even in the absence of hypertension, local production of Ang II could be involved in eye diseases. The goal of this manuscript is to review the most relevant scientific evidence supporting the role of the RAS activation, in the development of age-related macular degeneration and diabetic retinopathy, and highlight the importance of Ang II in the etiology of these diseases.

Marin Garcia, Pablo Jesus; Marin-Castano, Maria Encarna

2014-01-01

336

The immunological basis of hypertension.  

PubMed

A large number of investigations have demonstrated the participation of the immune system in the pathogenesis of hypertension. Studies focusing on macrophages and Toll-like receptors have documented involvement of the innate immunity. The requirements of antigen presentation and co-stimulation, the critical importance of T cell-driven inflammation, and the demonstration, in specific conditions, of agonistic antibodies directed to angiotensin II type 1 receptors and adrenergic receptors support the role of acquired immunity. Experimental findings support the concept that the balance between T cell-induced inflammation and T cell suppressor responses is critical for the regulation of blood pressure levels. Expression of neoantigens in response to inflammation, as well as surfacing of intracellular immunogenic proteins, such as heat shock proteins, could be responsible for autoimmune reactivity in the kidney, arteries, and central nervous system. Persisting, low-grade inflammation in these target organs may lead to impaired pressure natriuresis, an increase in sympathetic activity, and vascular endothelial dysfunction that may be the cause of chronic elevation of blood pressure in essential hypertension. PMID:25150828

Rodríguez-Iturbe, Bernardo; Pons, Héctor; Quiroz, Yasmir; Johnson, Richard J

2014-11-01

337

[Hypertensive effects of qat].  

PubMed

Chewing of Qat leaves which contain amphetamine alkaloids is a traditional drug practice in the horn of Africa. Cathine and cathinone are responsible for the desired psychogenic (suppression of hunger, mind stimulation, euphoria) and sympathicomimetic effects. In this study, we monitored seven volunteers during a traditional qat ritual. An increase in systolic and diastolic pressure was observed in three patients including one presenting predisposing chronic arterial hypertension. Peak pressure was observed approximately seven hours after beginning the ritual. The three patients presenting pressure changes were not significantly different from the four unaffected patients with regard to age or duration of qat use. These findings suggest that qat use by untreated hypertensive patients who react strongly to vasoconstrictive effects can lead to hypertension and resulting cardiovascular complications. PMID:10088104

Mion, G; Oberti, M; Ali, A W

1998-01-01

338

The role of intestinal mucosa injury induced by intra-abdominal hypertension in the development of abdominal compartment syndrome and multiple organ dysfunction syndrome  

PubMed Central

Introduction Abdominal distension is common in critical illness. There is a growing recognition that intra-abdominal hypertension (IAH) may complicate nonsurgical critical illness as well as after abdominal surgery. However, the pathophysiological basis of the injury to the intestinal mucosal barrier and its influence on the onset of abdominal compartment syndrome (ACS) and multiorgan dysfunction syndrome (MODS) remain unclear. We measured intestinal microcirculatory blood flow (MBF) during periods of raised intra-abdominal pressure (IAP) and examined how this influenced intestinal permeability, systemic endotoxin release, and histopathological changes. Methods To test different grades of IAH to the injury of intestinal mucosa, 96 New Zealand white rabbits aged 5 to 6 months were exposed to increased IAP under nitrogen pneumoperitoneum of 15 mmHg or 25 mmHg for 2, 4 or 6 hours. MBF was measured using a laser Doppler probe placed against the jejunal mucosa through a small laparotomy. Fluorescein isothiocyanate (FITC)-conjugated dextran was administered by gavage. Intestinal injury and permeability were measured using assays for serum FITC-dextran and endotoxin, respectively, after each increase in IAP. Structural injury to the intestinal mucosa at different levels of IAH was confirmed by light and transmission electron microscopy. Results MBF reduced from baseline by 40% when IAP was 15 mmHg for 2 hours. This doubled to 81% when IAP was 25 mmHg for 6 hours. Each indicator of intestinal injury increased significantly, proportionately with IAP elevation and exposure time. Baseline serum FITC-dextran was 9.30 (± SD 6.00) ?g/ml, rising to 46.89 (±13.43) ?g/ml after 15 mmHg IAP for 4 hours (P <0.01), and 284.59 (± 45.18) ?g/ml after 25 mmHg IAP for 6 hours (P <0.01). Endotoxin levels showed the same pattern. After prolonged exposure to increased IAP, microscopy showed erosion and necrosis of jejunal villi, mitochondria swelling and discontinuous intracellular tight junctions. Conclusions Intra-abdominal hypertension can significantly reduce MBF in the intestinal mucosa, increase intestinal permeability, result in endotoxemia, and lead to irreversible damage to the mitochondria and necrosis of the gut mucosa. The dysfunction of the intestinal mucosal barrier may be one of the important initial factors responsible for the onset of ACS and MODS. PMID:24321230

2013-01-01

339

[Methyldopa in therapy of hypertension in pregnant women].  

PubMed

Both chronic hypertensive disorders in pregnancy and pregnancy-induced hypertension are the main causes of morbidity and mortality of mothers and fetuses. The great significance in the prevention of serious complications of them has properly pharmacology treatment. One of the most early and the most often used drug is Methyldopa--a drug from the group acting via central nervous system, causing the depression in the cardio-vascular system. PMID:15108591

Seremak-Mrozikiewicz, Agnieszka; Drews, Krzysztof

2004-02-01

340

Angiotensinogen Gene Polymorphisms and Hypertension  

Microsoft Academic Search

Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure.\\u000a Hypertension affects 50 million Americans with a prevalence rate of 25–30% in the adult Caucasian population. The incidence\\u000a of hypertension and complications resulting from hypertension are even greater in the African-American population. The renin-angiotensin\\u000a system plays an important role in the regulation of

Ashok Kumar

341

Association between pregnancy-related hypertension and severity of hypertension.  

PubMed

Hypertension in pregnancy is an emerging sex-specific risk factor for cardiovascular disease and may lead to more severe hypertension after pregnancy. The objectives of this study were to investigate the frequency of pregnancy-related hypertension among patients referred to a hypertension clinic and its association with the severity of hypertension and evidence of end-organ damage. In this cross-sectional study, women with hypertension were submitted to a systematic clinical evaluation. The occurrence of pregnancy-related hypertension was investigated by questionnaire. The association between pregnancy-related hypertension and severity of hypertension (stage 2 according to Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII)) and end-organ damage was assessed in a logistic regression model. The mean age, systolic and diastolic blood pressure and body mass index (BMI) of the 768 women examined were 51.6+/-12.7 years, 158.2+/-26.6 mm Hg, 93.8+/-14.3 mm Hg and 29.4+/-5.6 kg/m(2), respectively. The proportion of women with pregnancy-related hypertension was 32.9%. It was significantly associated with hypertension at stage 2 (OR: 1.60, 95% CI: 1.14-2.24; P=0.01) after controlling for confounders. The occurrence of a pregnancy-related hypertension was not associated with evidence of optic fundi abnormalities, left ventricular hypertrophy or abnormalities in kidney function. In conclusion, pregnancy-related hypertension is frequent in women referred to a hypertension clinic, and is associated with severe hypertension but not with evidence of end-organ damage. PMID:19020534

Moreira, L B; Gus, M; Nunes, G; Gonçalves, C B C; Martins, J; Wiehe, M; Fuchs, F D

2009-06-01

342

Pregnancy-induced hypertension and diabetes and the risk of cardiovascular disease, stroke, and diabetes hospitalization in the year following delivery.  

PubMed

Although pregnancy events predict the long-term risk of chronic disease, little is known about their short-term impact because of the rarity of clinical events. We examined hospital discharge diagnoses linked to birth certificate data in the year following delivery for 849,639 births during 1995-2004 in New York City, New York. Adjusted odds ratios characterized the relationship between pregnancy complications and subsequent hospitalization for cardiovascular disease, stroke, and diabetes. Gestational hypertension was related to heart failure (adjusted odds ratio = 2.6, 95% confidence interval: 1.5, 4.5). Preeclampsia was related to all of the outcomes considered except type 1 diabetes, with adjusted odds ratios ranging from 2.0 to 4.1. Gestational diabetes was strongly related to the risk of subsequent diabetes (for type 1 diabetes, adjusted odds ratio = 40.4, 95% confidence interval: 23.8, 68.5; for type 2 diabetes, adjusted odds ratio = 22.6, 95% confidence interval: 16.9, 30.4) but to no other outcomes. The relationship of pregnancy complications to future chronic disease is apparent as early as the year following delivery. Moreover, elucidating short-term clinical outcomes offers the potential for etiological insights into the relationship between pregnancy events and chronic disease over the life course. PMID:24879314

Savitz, David A; Danilack, Valery A; Elston, Beth; Lipkind, Heather S

2014-07-01

343

[Glyceryl nitrates may cause hypertension].  

PubMed

The patient was an 82-year-old woman with orthostatism, who was administrated one normal dose of glyceryl nitrate as a part of a tilt table test. The following ten minutes after administration, a paradoxical and significant blood pressure response was registered in the form of a rise to 205/111 mmHg. The conclusion was that her response was a paradoxical response to glyceryl nitrate, orthostatism and a pathological response to massage of the carotid artery. This is the third reported case on paradoxical hypertension induced by glyceryl nitrates. It is speculated that dysfunction of the cerebral bloodflow autoregulation may be one of the causes of this phenomenon. PMID:21586249

Mørup, Peter; Levinsen, Tine Holbæk; Hovind, Peter

2011-05-16

344

A single exposure to particulate or gaseous air pollution increases the risk of aconitine-induced cardiac arrythmia in hypertensive rats  

EPA Science Inventory

Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

345

Early diastolic time intervals during hypertensive pregnancy.  

PubMed

Early diastolic time intervals have been assessed by means of the echopolycardiographic method in 17 pregnant women who developed hypertension during pregnancy (HP) and in 14 normal pregnant women (N). Systolic time intervals (STI), stroke volume (SV), ejection fraction (EF), and mean velocity of myocardial fiber shortening (VCF) were also evaluated. Recordings were performed in the left lateral decubitus (LLD) and then in the supine decubitus (SD). In LLD, isovolumic relaxation period (IRP) was prolonged in the hypertensive pregnant women compared with normal pregnant women (HP 51 +/- 12.5 ms, N 32.4 +/- 15 ms p less than 0.05), whereas time of the mitral valve maximum opening (DE) was not different in the groups. There was no difference in SV, EF, and mean VCF, whereas STI showed only a significant (p less than 0.05) lengthening of pre-ejection period (PEP) in HP. When the subjects shifted from the left lateral to the supine decubitus position, left ventricular ejection time index (LVETi) and SV decreased significantly (p less than 0.05) in both normotensive hypertensive pregnant women. IRP and PEP lengthened significantly (p less than 0.05) only in normals, whereas they were unchanged in HP. DE time did not vary in either group. In conclusion, hypertension superimposed on pregnancy induces lengthening of IRP, as well as of PEP, and minimizes the effects of the postural changes in preload on the above-mentioned time intervals. PMID:3665214

Spinelli, L; Ferro, G; Nappi, C; Farace, M J; Talarico, G; Cinquegrana, G; Condorelli, M

1987-10-01

346

Paranormal healing and hypertension  

Microsoft Academic Search

A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37),

Jaap J Beutler; Johannes T M Attevelt; Sybo A Schouten; Joop A J Faber; Evert J Dorhout Mees; Gijsbert G Geijskes

1988-01-01

347

Treatment of systemic hypertension  

PubMed Central

Systemic hypertension is a major risk factor for cardiovascular disease and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease. Double-blind, randomized, placebo-controlled trials have found that antihypertensive drug therapy reduces cardiovascular events in patients aged younger than 80 years and in patients aged 80 years and older in the Hypertension in the Very Elderly Trial. Although the optimal blood pressure treatment goal has not been determined, existing epidemiologic and clinical trial data suggest that a reasonable therapeutic blood pressure goal should be <140/90 mm Hg in patients younger than 80 years and a systolic blood pressure of 140-145 mm Hg if tolerated in patients aged 80 years and older. Non-pharmacologic lifestyle measures should be encouraged both to prevent development of hypertension and as adjunctive therapy in patients with hypertension. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, calcium channel blockers, and diuretics have all reduced cardiovascular events in randomized trials. The choice of specific drugs depends on efficacy, tolerability, presence of specific comorbidities, and cost. PMID:22937486

Aronow, Wilbert S

2012-01-01

348

Children and Hypertension.  

ERIC Educational Resources Information Center

Since children as young as seven years old can suffer from hypertension, all children should have blood pressure checked during physical examinations. Guidelines for testing children's blood pressure are presented along with suggestions about what schools and parents can do to help deal with the problem. (PP)

Carter, Denise

1983-01-01

349

Project "Hypertension Alert."  

ERIC Educational Resources Information Center

"Hypertension Alert," a 1979-80 blood pressure screening-awareness project of the Yonkers, New York Public Schools, is described. Data is analyzed in tables for ethnic composition, and range of blood pressure readings for the high school, junior high school, and elementary school students tested. (Author/JMK)

Sailors, Emma Lou

1983-01-01

350

[Update on endocrine hypertension].  

PubMed

Endocrine hypertension is the most common cause of secondary hypertension affecting ~3 % of the population, with primary hyperaldosteronism and pheochromocytoma being the principal conditions. Both diseases share an increased cardiovascular risk in comparison with essential hypertension patients (at the same blood pressure level). This augmented cardiovascular risk as well as the availability of specific treatment emphasize the importance of timely and correct diagnosis. Primary hyperaldosteronism, representing one tenth of hypertensive patients, is an under-diagnosed disease partly because of difficult diagnostic steps and absence of standard criteria. Recently, the description of somatic mutations in KCNJ5 gene in Conn adenomas had precipitated a resurgence of research activity to understand the pathophysiology of this common disease. Research had confirmed the role of these mutations in aldosterone hypersecretion; however, its role in adenoma formation is still to be elucidated. Elsewhere, much remains to be done in order to understand the pathogenesis of bilateral idiopathic hyperaldosteronism, the other common subtype of primary hyperaldosteronism. In pheochromocytoma, the revolution of genetics has led to major advances in the characterization of this rare disease. It is now clear that up to 50 % of patients with pheochromocytoma have a genetic abnormality and that different pheochromocytomas segregate into two clusters with distinct genotypes, signal transduction pathways and expression of biomarkers (phenotype). This continuing progress has huge effects on patient's management and follow-up. In this article we will shed light on the recent developments in both diseases with emphasis on their role in patient care. PMID:23089379

Al-Salameh, A; Cohen, R; Chanson, P; Plouin, P F

2012-10-01

351

Hypertension Research Division  

E-print Network

AT1 Receptors vasoconstriction Na Retention BP & end organ damage Drugs used to block RAS renin;Pablo Ortiz: Trafficking of the Na/K/2 Cl cotransporter and changes caused by hypertension AVP c: Mechanism by which Ac-SDKP prevents end organ damage and identifying its receptor #12;Suresh Palaniyandi

Berdichevsky, Victor

352

Sleep Apnea and Hypertension  

Microsoft Academic Search

\\u000a Sleep disordered breathing (SDB) encompasses all forms of respiratory disorders specific to sleep (1). There is a spectrum of SDB ranging from mild to severe with the most severe form being obstructive sleep apnea (OSA) (2). In adults, OSA has been linked to cardiovascular disease, specifically hypertension (HTN) (3). The association between systemic HTN and OSA is well documented in

Alisa A. Acosta

353

Hypertension, a health economics perspective.  

PubMed

The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment. PMID:19124418

Alcocer, Luis; Cueto, Liliana

2008-06-01

354

Reassessing the Impact of Smoking on Preeclampsia/Eclampsia: Are There Age and Racial Differences?  

PubMed Central

Objective To investigate the association between cigarette use during pregnancy and pregnancy-induced hypertension/preeclampsia/eclampsia (PIH) by maternal race/ethnicity and age. Methods This retrospective cohort study was based on the U.S. 2010 natality data. Our study sample included U.S. women who delivered singleton pregnancies between 20 and 44 weeks of gestation without major fetal anomalies in 2010 (n?=?3,113,164). Multivariate logistic regression models were fit to estimate crude and adjusted odds ratios and the corresponding 95% confidence intervals. Results We observed that the association between maternal smoking and PIH varied by maternal race/ethnicity and age. Compared with non-smokers, reduced odds of PIH among pregnant smokers was only evident for non-Hispanic white and non-Hispanic American Indian women aged less than 35 years. Non-Hispanic Asian/Pacific Islander women who smoked during pregnancy had increased odds of PIH regardless of maternal age. Non-Hispanic white and non-Hispanic black women 35 years or older who smoked during pregnancy also had increased odds of PIH. Conclusion Our study findings suggest important differences by maternal race/ethnicity and age in the association between cigarette use during pregnancy and PIH. More research is needed to establish the biologic and social mechanisms that might explain the variations with maternal age and race/ethnicity that were observed in our study. PMID:25337852

Chang, Jen Jen; Strauss, Jerome F.; Deshazo, Jon P.; Rigby, Fidelma B.; Chelmow, David P.; Macones, George A.

2014-01-01

355

Mechanisms and drug therapy of pulmonary hypertension at high altitude.  

PubMed

Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulmonary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension. PMID:23795732

Scherrer, Urs; Allemann, Yves; Rexhaj, Emrush; Rimoldi, Stefano F; Sartori, Claudio

2013-06-01

356

Comparison of survival in patients with pulmonary hypertension associated with fenfluramine to patients with primary pulmonary hypertension  

Microsoft Academic Search

To test whether the clinical presentation and prognosis of fenfluramine-induced pulmonary hypertension (PH) differs from primary PH (PPH), we compared the clinical profile and outcome of 10 patients with fenfluramine-induced PH with that of 70 patients with PPH referred to our center over the same time frame and treated identically. Patients with diet pill PH were similar to those with

Stuart Rich; Alicia Shillington; Vallerie McLaughlin

2003-01-01

357

Cilnidipine induced ankle edema.  

PubMed

Cilnidipine is a 4(th) generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema. PMID:24987189

Annil, Vishal R; Mahajan, Annil; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2014-01-01

358

Cilnidipine induced ankle edema  

PubMed Central

Cilnidipine is a 4th generation dihydropyridine calcium channel blocker approved recently for the treatment of essential hypertension. It is not known to present with ankle edema like amlodipine. Moreover, it has been proposed as an alternative anti-hypertensive for patients with amlodipine-induced edema. We report a case of cilnidipine induced ankle edema. PMID:24987189

Annil, Vishal R.; Mahajan, Annil; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2014-01-01

359

Anti-ischemic effects of angiotensin- converting enzyme inhibition in hypertension  

Microsoft Academic Search

OBJECTIVESWe investigated whether augmentation of bradykinin (BK) bioavailability with angiotensin-converting enzyme (ACE) inhibition is associated with reduced exercise-induced myocardial ischemia in hypertension.BACKGROUNDBradykinin responses are depressed in hypertension, and endothelial dysfunction contributes to myocardial ischemia by promoting abnormal coronary vasomotion during stress.METHODSFourteen hypertensive (HT) and 17 normotensive (NT), mildly symptomatic patients with coronary artery disease (CAD) and ST-segment depression during exercise

Abhiram Prasad; Rita Mincemoyer; Arshed A Quyyumi

2001-01-01

360

Pharmacologically induced release and modulation of /sup 3/H-norepinephrine (NE) from the isolated portal vein of the spontaneously hypertensive rat (SHR)  

SciTech Connect

The purpose of the present study was to probe the mechanism for the enhancement of the field-stimulation induced release of /sup 3/H-NE from blood vessels of the SHR compared to normotensive rats. The results of two types of experiments are reported here. First, the effect of nicotine as well as tyramine in inducing the release of /sup 3/H-NE from the superfused portal vein was compared to field stimulation. Secondly, the modulatory effect of serotonin (5-HT) and methacholine (M) on the field stimulation induced release of /sup 3/H-NE was examined. In contrast to the enhancement of the field stimulation induced release of /sup 3/H-NE from the portal vein of the SHR compared to WKY, both nicotine and tyramine produced a similar release of NE from blood vessel obtained from both strains. The fractional release of /sup 3/H-NE to 10/sup -4/, 10/sup -3/ and 10/sup -2/M nicotine was 0.21, 0.67 and 45.5 from WKY and 0.14, 0.68 and 42.4 from SHR. The fractional release of /sup 3/H-NE to 10/sup -4/ and 10/sup -3/M tyramine was 6 and 17 from WKY compared to 7.5 and 17.5 from SHR. The inhibition of /sup 3/H-NE release from the portal vein by both 5-HT and M was similar in blood vessels obtained from SHR and WKY. These results are consistent with there being a defect in the exocytotic induced release of NE from noradrenergic neurons at the vascular neuroeffector junction.

Zhang, S.Q.; Westfall, T.C.

1986-03-05

361

Is Gestational Hypertension Protective against Perinatal Mortality in Twin Pregnancies?  

PubMed Central

Background Pregnancy-induced or gestational hypertension is a common pregnancy complication. Paradoxically, gestational hypertension has been associated with a protective effect against perinatal mortality in twin pregnancies in analytic models (logistic regression) without accounting for survival time. Whether this effect is real remains uncertain. This study aimed to validate the impact of gestational hypertension on perinatal mortality in twin pregnancies using a survival analysis approach. Methods This was a retrospective cohort study of 278,821 twin pregnancies, using the U.S. 1995–2000 matched multiple birth dataset (the largest dataset available for multiple births). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death (stillbirth and neonatal death) comparing gestational hypertensive vs. non-hypertensive pregnancies controlling for maternal characteristics and twin cluster-level dependence. Results Comparing births in gestational hypertensive vs. non-hypertensive twin pregnancies, perinatal mortality rates were significantly lower (1.20% vs. 3.38%), so were neonatal mortality (0.72% vs. 2.30%) and stillbirth (0.48% vs. 1.10%) rates. The aHRs (95% confidence intervals) were 0.34 (0.31–0.38) for perinatal death, 0.31 (0.27–0.34) for neonatal death, and 0.45 (0.38–0.53) for stillbirth, respectively. The protective effect of gestational hypertension against perinatal death became weaker over advancing gestational age; the aHRs in very preterm (<32 weeks), mild preterm (32–36 weeks) and term (37+ weeks) births were 0.29, 0.48 and 0.76, respectively. The largest risk reductions in neonatal mortality were observed for infections and immaturity-related conditions. Conclusions Gestational hypertension appears to be beneficial for fetal survival in twin pregnancies, especially in those ending more prematurely or for deaths due to infections and immaturity-related conditions. Prospective studies are required to rule out the possibility of unmeasured confounders. PMID:24733364

Luo, Qi-Guang; Zhang, Ji-Yan; Cheng, Wei-Wei; Audibert, Francois; Luo, Zhong-Cheng

2014-01-01

362

Redox Signaling, Vascular Function, and Hypertension  

PubMed Central

Abstract Accumulating evidence supports the importance of redox signaling in the pathogenesis and progression of hypertension. Redox signaling is implicated in many different physiological and pathological processes in the vasculature. High blood pressure is in part determined by elevated total peripheral vascular resistance, which is ascribed to dysregulation of vasomotor function and structural remodeling of blood vessels. Aberrant redox signaling, usually induced by excessive production of reactive oxygen species (ROS) and/or by decreases in antioxidant activity, can induce alteration of vascular function. ROS increase vascular tone by influencing the regulatory role of endothelium and by direct effects on the contractility of vascular smooth muscle. ROS contribute to vascular remodeling by influencing phenotype modulation of vascular smooth muscle cells, aberrant growth and death of vascular cells, cell migration, and extracellular matrix (ECM) reorganization. Thus, there are diverse roles of the vascular redox system in hypertension, suggesting that the complexity of redox signaling in distinct spatial spectrums should be considered for a better understanding of hypertension. Antioxid. Redox Signal. 10, 1045–1059. PMID:18321201

Lee, Moo Yeol

2008-01-01

363

What constitutes controlled hypertension? Patient based comparison of hypertension guidelines  

Microsoft Academic Search

AbstractObjectives: To investigate and quantify the extent to which variations in guidelines influence assessment of control of hypertension.Design: Cross sectional study. Selected patients had hypertension assessed as controlled or uncontrolled with guidelines from New Zealand, Canada, the United States, Britain, and the World Health Organisation.Setting: 18 general practices in Oxfordshire.Subjects: 876 patients with diagnosed hypertension and taking antihypertensive drugs.Main outcome

T P Fahey; T J Peters

1996-01-01

364

Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy  

PubMed Central

Objectives We investigated the effect of reducing mitochondrial oxidative stress by the mitochondrial-targeted antioxidant peptide SS-31 in hypertensive cardiomyopathy. Background Oxidative stress has been implicated in hypertensive cardiovascular diseases. Mitochondria and NADPH oxidase have been proposed as primary sites of reactive oxygen species (ROS) generation. Methods The mitochondrial targeted antioxidant peptide SS-31 was used to determine the role of mitochondrial oxidative stress in Angiotensin II (Ang)-induced cardiomyopathy, as well as in G?q overexpressing mice with heart failure. Results Angiotensin II induces mitochondrial ROS in neonatal cardiomyocytes, which is prevented by SS-31, but not the non-targeted antioxidant N-acetyl cysteine (NAC). Continuous administration of Ang for 4 weeks in mice significantly increased both systolic and diastolic blood pressure, and this was not affected by SS-31 treatment. Ang was associated with upregulation of NADPH oxidase 4 (NOX4) expression, increased cardiac mitochondrial protein oxidative damage and induced the signaling for mitochondrial biogenesis. Reducing mitochondrial ROS by SS-31 substantially attenuated Ang-induced NOX4 upregulation, mitochondrial oxidative damage, upregulation of mitochondrial biogenesis, phosphorylation of p38 MAP kinase, and prevented apoptosis, concomitant with amelioration of Ang induced cardiac hypertrophy, diastolic dysfunction, and fibrosis, despite the absence of blood pressure lowering effect. NAC did not show any beneficial effect. SS-31 administration for 4 weeks also partially rescued the heart failure phenotype of G?q overexpressing mice. Conclusions Mitochondrial targeted peptide SS-31 ameliorates cardiomyopathy resulting from prolonged Ang stimulation as well as G?q overexpression, suggesting its potential clinical application for target organ protection in hypertensive cardiovascular diseases. PMID:21620606

Dai, Dao-Fu; Chen, Tony; Szeto, Hazel; Nieves-Cintron, Madeline; Kutyavin, Vassily; Santana, Luis F.; Rabinovitch, Peter S.

2013-01-01

365

HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats.  

PubMed

Histone deacetylases (HDACs) are transcriptional corepressors. Our recent study demonstrated that HDAC4 protein specifically increases in mesenteric artery from spontaneous hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY). Vascular inflammation is important for pathogenesis of hypertension. We examined whether HDAC4 affects vascular inflammatory responses and promotes hypertension. In vivo, blood pressure, reactive oxygen species (ROS) production, and VCAM-1 expression in isolated mesenteric artery were elevated in young SHR (7 wk old) compared with age-matched WKY, which were prevented by long-term treatment of SHR with an HDACs inhibitor, trichostatin A (TSA; 500 ?g·kg(-1)·day(-1) for 3 wk). In isolated mesenteric artery, the increased angiotensin II-induced contraction in SHR was reversed by TSA. The endothelium-dependent relaxation induced by ACh in SHR was augmented by TSA. In cultured rat mesenteric arterial smooth muscle cells (SMCs), expression of HDAC4 mRNA and protein was increased by TNF-? (10 ng/ml). TSA (10 ?M, pretreatment for 30 min) inhibited VCAM-1 expression and NF-?B phosphorylation induced by TNF (10 ng/ml, 24 h or 20 min) in SMCs. HDAC4 small interfering RNA inhibited TNF-induced monocyte adhesion, VCAM-1 expression, transcriptional activity of NF-?B, and ROS production in SMCs. The present results demonstrated that proinflammatory effects of HDACs may mediate the further development of hypertension in SHR. It is also suggested in cultured vascular SMCs that TNF-induced HDAC4 mediates vascular inflammation likely via VCAM-1 induction through ROS-dependent NF-?B activation. PMID:22389387

Usui, Tatsuya; Okada, Muneyoshi; Mizuno, Wataru; Oda, Mayuko; Ide, Natsuki; Morita, Tomoka; Hara, Yukio; Yamawaki, Hideyuki

2012-05-01

366

Relationship between elevated lipid peroxides, vitamin E deficiency and hypertension in preeclampsia  

Microsoft Academic Search

Preeclampsia or pregnancy-induced hypertension is a major cause of both maternal and fetal-neonatal morbidity and mortality. The deficiency of vitamin E can cause accumulation of lipid peroxidation products, which, in turn, can induce vasoconstriction. This study has examined any evidence of increased cellular lipid peroxidation and accumulation of malonydialdehyde (MDA, an end product of lipid peroxidation) in pregnancy-induced hypertension and

Sushil K. Jain; Rodney Wise

1995-01-01

367

Portal hypertension and variceal hemorrhage.  

PubMed

Portal hypertension, a major hallmark of cirrhosis, is defined as a portal pressure gradient exceeding 5 mm Hg. In portal hypertension, porto-systemic collaterals decompress the portal circulation and give rise to varices. Successful management of portal hypertension and its complications requires knowledge of the underlying pathophysiology, the pertinent anatomy, and the natural history of the collateral circulation, particularly the gastroesophageal varices. PMID:18387376

Toubia, Nagib; Sanyal, Arun J

2008-05-01

368

Portal hypertension with visceral leishmaniasis  

Microsoft Academic Search

We conducted this study to observe evidence of portal hypertension in children with visceral leishmaniasis (VL). Eighty-eight\\u000a consecutive cases (50 male) of VL were subjected to ultrasonography. Those with evidence of portal hypertension also underwent\\u000a upper gastrointestinal endoscopy and liver biopsy. Eight patients had portal hypertension as evidenced by dilated caliber\\u000a of portal and splenic veins. Two patients had periportal,

Rajniti Prasad; Utpal Kant Singh; O. P. Mishra; B. P. Jaiswal; Sunil Muthusami

2010-01-01

369

Epidemiology of pulmonary arterial hypertension.  

PubMed

Changes in the epidemiology of pulmonary arterial hypertension (PAH) have resulted from changes in classification schemes and an increased emphasis on diagnosis because of the availability of effective therapies. The terms primary pulmonary hypertension and secondary pulmonary hypertension are considered inappropriate, confusing, and should not be used. Recent registries of patients with PAH have provided improved data regarding prognosis in the era of advanced therapies. PMID:24267294

Taichman, Darren B; Mandel, Jess

2013-12-01

370

Platelet Aggregation in Portal Hypertension and Its Modification by Ultra-Low Doses of Aspirin  

Microsoft Academic Search

Aspirin (ASA) is widely accepted as antithrombotic drug, but several reports point out that its use in ultra-low doses (ULD) has prothrombotic properties. In this study, we evaluate the effect of portal hypertension in rats on platelet aggregation in an in vivo arterial thrombosis model induced by a laser beam. Portal hypertension was produced by calibrated stenosis of the portal

Francisco X. Eizayaga; Omar Aguejouf; Philippe Belon; Christian Doutremepuich

2005-01-01

371

Lack of protein kinase C-? leads to impaired urine concentrating ability and decreased aquaporin-2 in angiotensin II-induced hypertension.  

PubMed

Regulation of water and urea transport in the inner medullary collecting duct is essential for urine concentration. Aquaporin (AQP)2 water channels and urea transporter (UT)-A1 are inserted into the apical membrane upon phosphorylation of the channels to allow the transcellular movement of water and urea. Since ANG II activates PKC in many cell types, we tested the hypothesis that ANG II-induced regulation of water and urea transport is mediated by PKC. Osmotic minipumps delivered ANG II to wild-type (WT) or PKC-?(-/-) mice for 7 days. Inner medullas were harvested, and protein abundance was determined by immunoblot. ANG II increased systolic blood pressure to a similar degree in WT and PKC-?(-/-) mice. ANG II had no effect on the urine output of WT mice but increased that of PKC-?(-/-) mice. In accordance with observed differences in urine output, AQP2 abundance was unchanged in ANG II-treated WT animals but was decreased in PKC-?(-/-) mice. No change in membrane accumulation was seen. Phosphorylation of the cAMP-induced transcription factor CREB was decreased in PKC-?(-/-) mice in response to ANG II with no change in overall CREB abundance. ANG II did not alter the abundance of UT-A1 protein in WT or PKC-?(-/-) mice. Phosphorylation and overall abundance of tonicity-responsive enhancer-binding protein, a transcription factor that regulates UT-A1, were also unaltered by ANG II in either group. We conclude that PKC-? protects against ANG II-induced decreases in urine concentrating ability by maintaining AQP2 levels through CREB phosphorylation. PMID:22492943

Thai, Tiffany L; Blount, Mitsi A; Klein, Janet D; Sands, Jeff M

2012-07-01

372

Tumor Necrosis Factor-? Produced in the Kidney Contributes to Angiotensin II-dependent Hypertension.  

PubMed

Immune system activation contributes to the pathogenesis of hypertension and the resulting progression of chronic