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1

Parent-Offspring Conflict and the Persistence of Pregnancy-Induced Hypertension in Modern Humans  

PubMed Central

Preeclampsia is a major cause of perinatal mortality and disease affecting 5–10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved through the ability of fetal genes to increase maternal blood pressure as this enhances general nutrient supply. However, such mechanisms for inducing hypertension in pregnancy would need to incur sufficient offspring health benefits to compensate for the obvious risks for maternal and fetal health towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show that offspring exposed to pregnancy-induced hypertension (PIH) in trimester 1 had significantly reduced overall later-life disease risks, but increased risks when PIH exposure started or developed as preeclampsia in later trimesters. Similar patterns were found for first-year mortality. These results suggest that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health. PMID:23451092

Lykke, Jacob; Boomsma, Jacobus J.

2013-01-01

2

Serum calcium and magnesium levels in women presenting with pre-eclampsia and pregnancy-induced hypertension: a case¿control study in the Cape Coast metropolis, Ghana.  

PubMed

BackgroundHypertensive disorders of pregnancy are important causes of morbidity and mortality. The levels of calcium (Ca2+) and magnesium (Mg2+) in pregnancy may implicate their possible role in pregnancy-induced hypertension. This study assessed serum Ca2+ and Mg2+ levels in women with PIH (pregnancy-induced hypertension) and PE (pre-eclampsia), compared to that in normal pregnancy.MethodsThis case¿control study was conducted on 380 pregnant women (¿20 weeks gestation) receiving antenatal care at three hospitals in the Cape Coast metropolis, Ghana. This comprised 120 women with PIH, 100 women with PE and 160 healthy, age-matched pregnant women (controls). Demographic, anthropometric, clinical and obstetric data were gathered using an interview-based questionnaire. Venous blood samples were drawn for the estimation of calcium and magnesium.ResultsSystolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly raised in women with PIH (p¿=¿0.001) and PE (p¿=¿0.001). Women with hypertensive disorders (PE and PIH) had significantly lower serum calcium and magnesium levels than those in the control group (p¿<¿0.0001 each). Of those with PIH, SBP correlated positively with BMI (r¿=¿0.575, p¿<¿0.01) and Ca2+ correlated positively with Mg2+ (r¿=¿0.494, p¿<¿0.01). This was similar amongst the PE group for SBP and BMI as well as for Ca2+and Mg2+ but was not significant. Multivariate analysis showed that women aged ¿40 years were at a significant risk of developing PIH (OR¿=¿2.14, p¿=¿0.000).ConclusionIn this study population, serum calcium and magnesium levels are lower in PIH and PE than in normal pregnancy. Mineral supplementation during the antenatal period may influence significantly, the occurrence of hypertensive disorders in pregnancy. PMID:25410280

Ephraim, Richard; Osakunor, Derick; Denkyira, Seth; Eshun, Henrietta; Amoah, Samuel; Anto, Enoch

2014-11-20

3

(pih11\\/2)  

Microsoft Academic Search

Predictions are made for the spectra associated with the ( pih 11\\/2) n configuration when n=4, 5 and 6. Since{64\\/146}Gd82 acts as if it is a closed shell, these states are expected to be low-lying in the nuclei{68\\/150}Er82,{69\\/151}Tm82 and{70\\/152}Yb82. The residual h 11\\/2 interaction is taken from the experimental spectrum of{66\\/148}Dy82 and it is shown that this conserves seniority to

R. D. Lawson

1981-01-01

4

Proteinuria in hypertensive pregnancy diseases is associated with a longer persistence of hypertension postpartum.  

PubMed

As there is growing evidence that hypertensive pregnancy disorders are associated with a risk of cardiovascular diseases later, the resolution of hypertension postpartum (PP) is of high clinical significance. However, there is little knowledge about the factors that influence this normalization. The objectives of our study were (a) to investigate whether or not there are differences in the resolution of hypertension between the distinct types of hypertensive pregnancy disorders and (b) to analyse what clinical parameters may determine the resolution pattern PP. In this retrospective study, 52 patients with preeclampsia (PE), seven with HELLP syndrome (haemolysis, elevated liver enzymes, low platelets), 10 with chronic hypertension (CH) and 21 with pregnancy-induced hypertension (PIH) were recruited. The course of the clinical parameters until day 7 PP was documented. Patients with proteinuria (PE/HELLP) showed the highest blood pressure values PP, while patients with PIH and CH showed no blood pressure changes up to day 7 PP. In patients with proteinuric diseases, there was a significantly higher percentage of cases with persisting hypertension at day 3 PP (71% vs 48% PIH/CH group, P<0.05), and even at day 7 PP this percentage remained significantly higher (31% vs 19% PIH/CH group). Our study shows that patients with proteinuric pregnancy disorders have a delayed PP of hypertension. A high percentage of these women are discharged from hospital with persisting hypertension and proteinuria. These observations demand a more specific and long-term PP care for these women. PMID:16239899

Stepan, H; Nordmeyer, A K; Faber, R

2006-02-01

5

Maternal Chronic HBV Infection Would Not Increase the Risk of Pregnancy-Induced Hypertension – Results from Pregnancy Cohort in Liuyang Rural China  

PubMed Central

The relationship between maternal HBV (hepatitis B virus) infection and pregnancy-induced hypertension (PIH) is inconclusive. Few studies have been conducted in rural areas of China. In order to examine the association between maternal chronic HBV infection and risk of PIH in Liuyang rural area China, we enrolled 6,195 eligible pregnant women in 2010–2011 in selected 14 towns of Liuyang on their first prenatal visit to local maternity care unit. A total of 461 subjects (7.44% (95%CI: 6.79%, 8.10%)) were identified with positive HBsAg status (exposed group) and 5734 were non-HBV carriers (unexposed group). Multivariate log-binomial regression models were used to estimate the risk of PIH, gestational hypertension (GH), and preeclampsia (PE) in relation to maternal chronic HBV infection. There are total of 455 subjects diagnosed with PIH (7.34% (95%CI: 6.70%, 7.99%)), including 371 GH (5.99% (95%CI: 5.40%, 6.58%)) and 81 PE (1.31% (95%CI: 1.07%, 1.64%)). The crude risk ratio between PIH, GH, PE and maternal HBV infection were 1.20 (95%CI: 0.88, 1.64), 1.30(95%CI: 0.93, 1.81) and 0.79 (95%CI: 0.32, 1.93), respectively. After adjustment for gravidity history, abortion history, family history of Diabetes Mellitus (DM) and family history of hypertension, positive HBsAg status was still not significantly associated with PIH (RR?=?1.18, 95%CI: 0.87, 1.62), GH (RR?=?1.27, 95%CI: 0.91, 1.78) or PE (RR?=?0.79, 95%CI: 0.32, 1.95). Additional adjustment for maternal age, marital status, parity history, family history of DM, Body Mass Index at first antenatal visit, folic acid supplementation, smoking status during pregnancy and economic status of living area, multivariate analysis provided similar results. In conclusion, our study found that maternal chronic HBV infection prevalence rate is 7.4% among Liuyang rural area and there is no significant association between maternal HBV infection and the risk of PIH, GH or PE. PMID:25479003

Huang, Xin; Tan, Hongzhuan; Li, Xun; Zhou, Shujin; Wen, Shi Wu; Luo, Meiling

2014-01-01

6

Pheochromocytoma induced hypertension.  

PubMed

Pheochromocytoma (Pheo) is a rare tumor that develops in the core of a chromaffin cell. This article will focus on pheochromocytoma and its affect on the heart. Because the signs and symptoms of a pheochromocytoma are those of the sympathetic nervous system, this tumor is hard to detect and might not be considered early on. In addition, there are many common deferential diagnoses that may lead to a delay of the correct diagnosis of a pheochromocytoma. Uncontrollable hypertension is one of the primary effects of pheochromocytoma. A severe increase in blood pressure (hypertensive crisis) may occur and this can be a life threatening condition that leads to stroke or arrhythmias. African-Americans are disproportionately affected by hypertension and they often go undiagnosed because of a lack of resources or access to care. This tumor is difficult to detect and its effects often mimic many other diagnoses, which often leads to this tumor being a late consideration. The long-term effects of a pheochromocytoma can lead to damage to the heart muscle, congestive heart failure (CHF), increased risk of diabetes, and even death. Nurses need to be aware of the key signs and symptoms of a pheochromocytoma, and to know when testing for this tumor what symptoms should be considered. Patients who suffer from a diagnosis of this tumor need a lot of emotional support and they must follow a strict diet and medication regimen. Nurses can play a vital role in raising awareness in our community about this tumor as well as being a patient advocate. PMID:21516925

Andrews, Deborah

2010-12-01

7

Drug-induced hypertension: an unappreciated cause of secondary hypertension.  

PubMed

A myriad variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure, or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, or an increase in pressure may be encountered after their discontinuation. In general, drug-induced pressure increases are small and transient: however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. The deleterious effect of therapeutic agents is more pronounced in patients with preexisting hypertension, in those with renal failure, and in the elderly. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and facilitate antihypertensive therapy. Once chemical-induced hypertension has been identified, discontinuation of the causative agent is recommended, although hypertension can often be managed by specific therapy and dose adjustment if continued use of the offending agent is mandatory. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. PMID:22195528

Grossman, Ehud; Messerli, Franz H

2012-01-01

8

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. PMID:25405062

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

2014-01-01

9

Drugs induced pulmonary arterial hypertension.  

PubMed

Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

2013-09-01

10

The Borderline Hypertensive Rat: A Model for Studying the Mechanisms of Environmentally Induced Hypertension  

Microsoft Academic Search

The borderline hypertensive rat (BHR) is a first-generation cross between the spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat. The BHR develops frank hypertension when chronically stressed or when fed a high-sodium diet. Stress-induced hypertension can be blocked by exercise.The role of the central nervous system and kidney in hypertension development in this model is discussed.

James E. Lawler; Ronald H. Cox; Brian J. Sanders; Vicki P. Mitchell

1988-01-01

11

Bevacizumab-induced hypertension: pathogenesis and management.  

PubMed

Bevacizumab, a recombinant humanized monoclonal antibody targeting the vascular endothelial growth factor (VEGF), has been approved in the US as first- and second-line treatment of colorectal cancer and in the first-line treatment of advanced non-small cell lung cancer. The US FDA has also granted approval for the use of bevacizumab for the treatment of patients with metastatic renal cell carcinoma and glioblastoma, and in Europe, it is also approved in metastatic breast cancer in combination with paclitaxel. Bevacizumab is under investigation in the first-line and adjuvant setting of almost all types of solid tumors. However, anti-VEGF therapy is associated with significant toxicity. The incidence of grade 3-4 hypertension differs among the various malignancies in which bevacizumab is administered, possibly because of drug interactions with co-administered chemotherapy drugs. Hypertension appears to be dose dependent, and it is under investigation as a biomarker for VEGF inhibition efficacy. There are three main theories concerning the underlying pathophysiology: (i) the nitric oxide theory; (ii) the renal impairment theory; and (iii) the pre-eclampsia-like theory. The correct evaluation of the levels of hypertension is of critical importance and home blood pressure monitoring seems to be the most effective technique. A baseline assessment and follow-up monitoring of blood pressure is considered necessary for all patients receiving bevacizumab. There are no evidence-based recommendations regarding which antihypertensives are more appropriate for the management of bevacizumab-related hypertension. It has been suggested that the benefits from antihypertensive treatment are largely independent of the drugs used, as long as they adequately lower blood pressure. Randomized prospective studies are necessary to provide data that will be useful for the development of specific guidelines for the management of bevacizumab-related hypertension. In the meantime, treatment of anti-VEGF-induced hypertension should follow current guidelines for diagnosis and management of hypertension in general. PMID:21627340

Syrigos, Kostas N; Karapanagiotou, Eleni; Boura, Paraskevi; Manegold, Christian; Harrington, Kevin

2011-06-01

12

Xanthine oxidase activity in the dexamethasone-induced hypertensive rat  

Microsoft Academic Search

Hypertension may be associated with an increase in oxidative stress as a possible mechanism for the increased vascular tone and organ injury. Previously, we reported an increased production of reactive oxygen species and endothelial cell death in the microcirculation of hypertensive rats. We hypothesize that xanthine oxidase (XO) may be a potential source of oxidants induced by glucocorticoid-induced hypertension. Male

Camille J Wallwork; Dale A Parks; Geert W Schmid-Schönbein

2003-01-01

13

[Role of platelet microaggregates in thrombocytopenia in normal and hypertensive pregnancy].  

PubMed

Platelet count and parameters (mean volume, MPV; volume distribution width, PDW; percent of large elements, PLCR) were examined at the third trimester, at delivery, at days 1 and 4 puerperium, in 9 primigravidae with idiopathic thrombocytopenia and 11 with pregnancy-induced hypertension (PIH) with associated thrombocytopenia, and compared with those from 27 PIH and 22 normotensive, normothrombocytemic primigravidae. All hypertensive women were treated with nifedipine alone or associated to methyldopa, clonidine or labetalol. Platelet count tends to a progressive fall during normal pregnancy, and to rough rise in puerperium, the remaining parameters being unchanged. In idiopathic thrombocytopenia the reduced count remains unchanged even in puerperium, and the increased MPV and PLCR are consistent with the presence of large, immature, circulating elements, in pregnancy as well as in puerperium. When thrombocytopenia is associated to PIH, puerperal recovery is maximum. In this case, the drop in MPV and PLCR is consistent with the resolution of microaggregates that may produce artifact in the evaluation of platelet parameters. The presence of platelet microaggregates may therefore cause overestimation of thrombocytopenia associated to PIH. PMID:1817443

Tranquilli, A L; Fiorini, E; Pignanelli, A; Garzetti, G G; Romanini, C

1991-01-01

14

Impairment of vascular function in cold stress induced hypertension  

Microsoft Academic Search

There are a number of epidemiological studies reporting seasonal variability of blood pressure. Colder seasons causing high blood pressure are found in both hypertensive and normotensive subjects. The mechanisms for cold-induced hypertension (CIH) are poorly understood. To investigate the role of cold stress in the development and maintenance of hypertension, Three month old Wistar rats were randomly divided into two

Zhiming Zhu; Changqing Yu; Lijuan Wang; Haiyan Wang; Shanjun Zhu

2002-01-01

15

Exercise-induced Pulmonary Hypertension  

PubMed Central

Exercise stresses the pulmonary circulation through increases in cardiac output (Q.) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)–flow relationships ranges from 0.5 to 3 mm Hg?min?L?1. The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a Q. of less than 10 L?min?1 or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP–flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase Q. at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology. PMID:23348976

Vanderpool, Rebecca; Dhakal, Bishnu P.; Saggar, Rajeev; Saggar, Rajan; Vachiery, Jean-Luc; Lewis, Gregory D.

2013-01-01

16

Genetic Predisposition and Stress-Induced Hypertension  

Microsoft Academic Search

When chronically exposed to an approach-avoidance conflict, rats with a genetic susceptibility to hypertension showed persistent elevations in systolic blood pressure, but rats with a genetic resistance to hypertension did not. Hence, psychic stress is selectively efficacious in producing hypertensive effects depending on genetic predisposition of the animal.

Richard Friedman; Junichi Iwai

1976-01-01

17

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

Federal Register 2010, 2011, 2012, 2013

...Public Comment for: Capture Energy Efficiency Measures for PIH AGENCY: Office...HUD is creating the Capture Energy Efficiency Measures for PIH (CEEMP) data...Title of Proposal: Capture Energy Efficiency Measures for PIH...

2011-12-07

18

Diuretic induced hyponatraemia in elderly hypertensive women  

Microsoft Academic Search

Diuretics are recommended as first-line antihypertensive treatment in elderly patients. Although attention is usually paid to prevent hypokalaemia with diuretic therapy, risk of hyponatraemia is often ignored. We performed this study to characterise hypertensive patients at increased risk to develop hyponatraemia. We reviewed charts of hypertensive patients hospitalised in Chaim Sheba Medical Center for hyponatraemia from 1990 to 1997. Patients

Y Sharabi; R Illan; Y Kamari; H Cohen; M Nadler; F H Messerli; E Grossman

2002-01-01

19

Effect of diazepam (Valium ® ) on chronic stress-induced hypertension in the rat  

Microsoft Academic Search

Summary Chronic treatment with diazepam was effective in preventing chronic stress-induced hypertension in rats. It also prevented the stressful stimuli from maintaining a hypertensive level in animals previously made hypertensive by chronic stress.

M. Segal

1981-01-01

20

Mitochondrial injury and dysfunction in hypertension-induced cardiac damage.  

PubMed

Hypertension remains an important modifiable risk factor for cardiovascular disease, associated with increased morbidity and mortality. Deciphering the mechanisms involved in the pathogenesis of hypertension is critical, as its prevalence continues increasing worldwide. Mitochondria, the primary cellular energy producers, are numerous in parenchymal cells of the heart, kidney, and brain, major target organs in hypertension. These membrane-bound organelles not only maintain cellular respiration but also modulate several functions of the cell including proliferation, apoptosis, generation of reactive oxygen species, and intracellular calcium homeostasis. Therefore, mitochondrial damage and dysfunction compromise overall cell functioning. In recent years, significant advances increased our understanding of mitochondrial morphology, bioenergetics, and homeostasis, and in turn of their role in several diseases, so that mitochondrial abnormalities and dysfunction have been identified in experimental models of hypertension. In this review, we summarize current knowledge of the contribution of dysfunctional mitochondria to the pathophysiology of hypertension-induced cardiac damage, as well as available evidence of mitochondrial injury-induced damage in other organs. Finally, we discuss the capability of antihypertensive therapy to ameliorate hypertensive mitochondrial injury, and the potential position of mitochondria as therapeutic targets in patients with hypertension. PMID:25385092

Eirin, Alfonso; Lerman, Amir; Lerman, Lilach O

2014-12-01

21

Endothelial dysfunction in cold-induced hypertensive rats  

Microsoft Academic Search

Endothelial dysfunction can be observed in preatherosclerotic conditions. However, its pathogenetic role in hypertension is still controversial. Endothelial-dependent changes of blood pressure (BP) and expression of endothelial nitric oxide synthase (eNOS) were evaluated in cold-induced hypertensive rats. Wistar rats were exposed to cold stress for 8 weeks. Exposure to cold stress significantly increased the systolic BP in rats. The infusion

Zhiming Zhu; Shanjun Zhu; Jijun Zhu; Markus van der Giet; Martin Tepel

2002-01-01

22

Role of Neuropeptide Y in Cold Stress-Induced Hypertension  

Microsoft Academic Search

Han, S. P., X. Chen, B. Cox, C.-L. Yang, Y.-M. Wu, L. Naes and T. C. Westfall. Role of neuropeptide Y in cold stress-induced hypertension. Peptides 19(2) 351–358, 1998.—Chronic cold stress (4°C) produced a sustained increase in mean arterial pressure in both normotensive and borderline hypertensive rats (BHR). The high blood pressure in BHRs was significantly reversed by a neuropeptide

Songping Han; Xiaoli Chen; Bryan Cox; Chun-lian Yang; Yu-mei Wu; Linda Naes; Thomas Westfall

1998-01-01

23

Tempol prevents and reverses glucocorticoid-induced hypertension  

Microsoft Academic Search

The aims of present study were to investigate the effects of Tempol (4-hydroxy-2,2,6,6,-tetramethylpiperidine-N-oxyl), a membrane-permeable superoxide scavenger, on prevention and reversal of glucocorticoid (GC)-induced hypertension in the rat.Two models were used, adrenocorticotropic hormone (ACTH) treatment which produces hypertension through increase in corticosterone secretion, and the synthetic GC dexamethasone (Dex). Male Sprague-Dawley rats (n=10 in each group) were treated with saline,

Yi Zhang; Ryan Jang; Trevor Mori; Kevin Croft; Christopher G. Schyvens; Judith A. Whitworth

2003-01-01

24

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

25

Stress-induced gastric lesions in spontaneously hypertensive rats  

Microsoft Academic Search

Studies were conducted to determine the roles of the parasympathetic and the sympathetic nerves in the induction of gastric hemorrhagic lesions induced by cold-plus-restraint stress in spontaneously hypertensive rats (SHR). After bilateral vagotomy or reserpine treatment, partial reduction in the incidence and severity (per stomach) of gastric lesions was observed. Pretreatment with vagotomy plus reserpine, levodopa, or levodopa plus reserpine

Marvin M. Goldenberg

1974-01-01

26

Laser-Induced Mouse Model of Chronic Ocular Hypertension  

E-print Network

) is considered a primary risk factor for the initiation and progression of glaucomatous neuropathy.2 However human diseases could provide an opportunity to identify possible risk factors that may predispose to andLaser-Induced Mouse Model of Chronic Ocular Hypertension Sinisa D. Grozdanic,1,2 Daniel M. Betts,1

Sakaguchi, Donald S.

27

Vasculoprotective effect of cilostazol in aldosterone-induced hypertensive rats  

Microsoft Academic Search

Cilostazol (CILO), a selective inhibitor of phosphodiesterase 3 with potent antithrombotic property, has been shown to have a vasculoprotective effect in atherosclerosis animal models due to its potential anti-inflammatory and antioxidant actions. This study was undertaken to investigate whether CILO has in fact any vasculoprotective effects in aldosterone-induced hypertensive rats (Aldo-rats), and whether CILO affects Aldo-induced oxidative stress, nitric oxide

Maya Sakurada; Takanobu Yoshimoto; Naoko Sekizawa; Yuki Hirono; Noriko Suzuki; Yukio Hirata

2010-01-01

28

Racial Differences in Stress-Induced Cardiovascular Reactivity and Hypertension: Current Status and Substantive Issues  

Microsoft Academic Search

Essential hypertension is perhaps the number-one health problem of Black Americans. Research has indicated that stress-induced cardiovascular hyperreactivity may be a significant contributor to essential hypertension. The high prevalence of hypertension among Blacks suggests that this group, in comparison with Whites, may be particularly susceptible to cardiovascular hyperreactivity. The first portion of this article reviews research to date that has

Norman B. Anderson

1989-01-01

29

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

Microsoft Academic Search

Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg\\u000a in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters\\u000a related to hypertension in ISIAH. Kidneys, adrenals, and systemic endocrine parameters were studied in ISIAH of different\\u000a ages and compared to normotensive Wistar albino Glaxo (WAG) rats. Native organs

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

2006-01-01

30

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

31

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

32

Aldosterone Acting through the CNS Sensitizes Angiotensin II -Induced Hypertension  

PubMed Central

Previous studies have shown that preconditioning rats with a non-pressor dose of angiotensin II (AngII) sensitizes the pressor response produced by later treatment with a higher dose of AngII and that AngII and aldosterone (Aldo) can modulate each other’s pressor effects through actions involving the central nervous system (CNS). The current studies tested whether Aldo can cross-sensitize the pressor actions of AngII to enhance hypertension by employing an Induction-Delay-Expression (I-D-E) experimental design. Male rats were implanted for telemetered BP recording. During I, sub-pressor doses of either sc or icv Aldo were delivered for 1 week. Rats were then rested for 1 week (D) to assure that any exogenous Aldo was metabolized. After this, AngII was given sc for 2 weeks (E). During I and D Aldo had no sustained effect on BP. However, during E AngII-induced hypertension was greater in the groups receiving sc or icv Aldo during I in comparison to those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of D and E showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after AngII, and there was greater Fra-like immunoreactivity present at the end of E in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of AngII-induced hypertension probably by mechanisms that involve the CNS. PMID:22949534

Xue, Baojian; Zhang, Zhongming; Roncari, Camila F.; Guo, Fang; Johnson, Alan Kim

2012-01-01

33

Structural Basis for Phosphorylation-Dependent Recruitment of Tel2 to Hsp90 by Pih1  

PubMed Central

Summary Client protein recruitment to the Hsp90 system depends on cochaperones that bind the client and Hsp90 simultaneously and facilitate their interaction. Hsp90 involvement in the assembly of snoRNPs, RNA polymerases, PI3-kinase-like kinases, and chromatin remodeling complexes depends on the TTT (Tel2-Tti1-Tti2), and R2TP complexes—consisting of the AAA-ATPases Rvb1 and Rvb2, Tah1 (Spagh/RPAP3 in metazoa), and Pih1 (Pih1D1 in humans)—that together provide the connection to Hsp90. The biochemistry underlying R2TP function is still poorly understood. Pih1 in particular, at the heart of the complex, has not been described at a structural level, nor have the multiple protein-protein interactions it mediates been characterized. Here we present a structural and biochemical analysis of Hsp90-Tah1-Pih1, Hsp90-Spagh, and Pih1D1-Tel2 complexes that reveal a domain in Pih1D1 specific for binding CK2 phosphorylation sites, and together define the structural basis by which the R2TP complex connects the Hsp90 chaperone system to the TTT complex. PMID:24794838

Pal, Mohinder; Morgan, Marc; Phelps, Sarah E.L.; Roe, S. Mark; Parry-Morris, Sarah; Downs, Jessica A.; Polier, Sigrun; Pearl, Laurence H.; Prodromou, Chrisostomos

2014-01-01

34

Neuroendocrine profiling in inherited stress-induced arterial hypertension rat strain with stress-sensitive arterial hypertension  

Microsoft Academic Search

The functions of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems were studied in rats with inherited stress-induced arterial hypertension (ISIAH strain).A characteristic feature ofthe ISIAH strainisanincrease in arterial blood pressure measured both under basal conditions and after restraint stress in particular. In the control ISIAH rats, the basal plasma ACTH concentration was slightly lower than that in the

A L Markel; O E Redina; M A Gilinsky; G M Dymshits; E V Kalashnikova; Yu V Khvorostova; L A Fedoseeva; G S Jacobson

2007-01-01

35

Genetic predisposition and stress-induced hypertension. [Rats  

Microsoft Academic Search

When chronically exposed to an approach-avoidance conflict, rats with a genetic susceptibility to hypertension showed persistent elevations in systolic blood pressure, but rats with a genetic resistance to hypertension did not. Hence, phychic stress is selectively efficacious in producing hypertensive effects depending on genetic predisposition of the animal.

R. Friedman; J. Iwai

1976-01-01

36

Roles of central interleukin-1 on stress-induced-hypertension and footshock-induced-analgesia in rats  

Microsoft Academic Search

Central interleukin-1 (IL-1) plays an important role in mediating the neural, endocrine, and behavioral responses to stressors. Here we tested whether central IL-1 is involved in stress-induced hypertension or footshock (FS)-induced-analgesia. We observed that: (1) intracerebral ventricular injection of (ICV) IL-1? induced pressor responses; (2) hypertension induced by IL-1? was blocked by ICV an IL-1 antagonist, IL-1ra; (3) ICV IL-1ra

Chang-Jiang Zou; Jin-Dong Liu; Yi-Chun Zhou

2001-01-01

37

Glucocorticoid-induced hypertension in the elderly relation to serum calcium and family history of essential hypertension  

Microsoft Academic Search

To explore the syndrome of glucocorticoid-induced hypertension in the elderly, we analyzed the clinical findings from 35 patients aged more than 65 years (12 men, 23 women) who received glucocorticoid therapy. Resting blood pressures (BP) were less than 140\\/90 mm Hg before glucocorticoid therapy, and patients were apparently disease-free apart from the condition for which glucocorticoid therapy was prescribed. Glucocorticoid-induced

Atsuhisa Sato; John W. Funder; Michihito Okubo; Eiji Kubota; Takao Saruta

1995-01-01

38

The risk of pregnancy-induced hypertension: black and white differences in a military population.  

PubMed Central

The relationship between race and risk of pregnancy-induced hypertension was investigated in a cohort of active-duty military women who gave birth during the period 1987 through 1989. Cases were identified through hospital discharge diagnoses and included transient gestational hypertension, pre-eclampsia, eclampsia, and unspecified hypertension complicating pregnancy. Multivariate analysis showed nulliparous Black women to be at a slightly increased risk for all pregnancy-induced hypertension (risk ratio [RR] = 1.2) and for pre-eclampsia (RR = 1.3) compared with nulliparous White women. Black parous women were found to have a slightly reduced risk of all pregnancy-induced hypertension (RR = 0.77) and pre-eclampsia (RR = 0.38) compared with White parous women. PMID:8092384

Irwin, D E; Savitz, D A; Hertz-Picciotto, I; St André, K A

1994-01-01

39

Shear Stress-Induced Release of Prostaglandin H2 in Arterioles of Hypertensive Rats  

Microsoft Academic Search

The nitric oxide-mediated portion of shear stress-induced dilation of rat gracilis muscle arterioles was shown to be impaired in spontaneously hypertensive rats (SHR). Because shear stress-induced dilation is primarily mediated by endothelium-derived prostaglandins in rat cremasteric arterioles, we hypothesized that in the cremasteric vascular bed the mediation of shear stress-induced dilation by prostaglandins is altered in hypertension. At a constant

An Huang; Dong Sun; Akos Koller

40

Role of Oxidative Stress in Erythropoietin-Induced Hypertension in Uremic Rats  

Microsoft Academic Search

BackgroundErythropoietin (EPO) administration in uremic rats leads to an increase in blood pressure (BP). Because chronic renal failure has been associated with oxidative stress, we hypothesize that EPO treatment could accentuate this condition and contribute to hypertension. The present study was designed to investigate the role of reactive oxygen species in EPO-induced hypertension and the effect of tempol, a superoxide

Marie-Eve Rancourt; Marie-Eve Rodrigue; Mohsen Agharazii; Richard Larivière; Marcel Lebel

2010-01-01

41

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

PubMed Central

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

2013-01-01

42

[Cold-induced changes in blood lipoproteins in normotensive and hypertensive rats].  

PubMed

It is shown that in thermoneutral conditions ISIAH (Inherited Stress-Induced Arterial Hypertension) hypertensive rats had a lower level of high-density lipoproteins (HDLP) in plasma and a higher atherogenic coefficient compared to normotensive Wistar rats. After cooling there were different changes in fractional composition of plasma lipoproteins both in normo- and hypertensive rats. These changes depended on the cooling rate and were more pronounced after slow cooling. Slow cooling resulted in a more significant increase of plasma HDLP and in a greater decrease in LDLP and atherogenic coefficient in hypertensive rats compared to normotensive ones. PMID:16607890

Kozyreva, T V; Lomakina, S V; Tuzikov, F V; Tuzikova, N A

2006-01-01

43

Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets  

Microsoft Academic Search

Recent studies have demonstrated that the feeding of low protein diets to rats during pregnancy induces hypertension in their offspring. Maternal-diet-induced hypertension has been previously associated with elevated pulmonary angiotensin converting enzyme (ACE) activity. In the present study, the importance of the renin angiotensin system, and in particular ACE, in the maintenance of the hypertensive state, is investigated. Pulmonary and

Simon C. Langley-Evans; Alan A. Jackson

1995-01-01

44

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.  

PubMed

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. PMID:25497573

Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

2015-02-01

45

IgG Receptor Fc?RIIB Plays a Key Role in Obesity-Induced Hypertension.  

PubMed

There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fc? receptor IIB (Fc?RIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that Fc?RIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that Fc?RIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas Fc?RIIB(+/+) mice developed obesity-induced hypertension, Fc?RIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; Fc?RIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an Fc?RIIB-dependent process. Thus, we have identified a novel role for Fc?RIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting Fc?RIIB may potentially offer new means to treat hypertension in obese individuals. PMID:25368023

Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

2015-02-01

46

Protection of blood-brain barrier breakdown by nifedipine in adrenaline-induced acute hypertension.  

PubMed

The question of whether influxes of ionic Ca+2 into cerebral endothelium plays an important role in increased vascular permeability consequent to an acute hypertension is not accurately resolved. We tested the effect of nifedipine, a calcium entry blocker, on the cerebrovascular permeability for proteins in adrenalin-induced acute hypertension. The experiments were carried out on male Wistar rats. The experimental groups consisted of normotensive saline controls, adrenaline-induced hypertensive rats, and adrenalin-induced hypertensive rats as pre-treated or post-treated with a bolus of nifedipine. Brains of hypertensive rats showed increased permeability to Evans Blue-Albumin complex, when blood pressure elevated rapidly to more than 170 mmHg. The number and size of areas of Evans-Blue extravasation were smaller if an increase in blood pressure was prevented. The short lasting elevation of blood pressure did not result in protein extravasation in brains of hypertensive rats. The results suggest that nifedipine can modify the permeability disruptions observed in acutely hypertensive rats. The data also support the hypothesis that Ca+2 may be responsible for the changes in permeability of BBB in hypertension by mediating the contraction of vascular muscles. PMID:15195355

Nukhet Turkel, A; Ziya Ziylan, Y

2004-04-01

47

Nitric Oxide Synthase Expression in the Course of Lead-Induced Hypertension  

Microsoft Academic Search

We recently showed elevated reactive oxygen species (ROS), reduced urinary excretion of NO metabolites (NOx), and increased NO sequestration as nitrotyrosine in various tissues in rats with lead-induced hypertension. This study was designed to discern whether the reduction in urinary NOx in lead-induced hypertension is, in part, due to depressed NO synthase (NOS) expression. Male Sprague-Dawley rats were randomly assigned

Nosratola D. Vaziri; Yaoxian Ding; Zhenmin Ni

48

Aspirin Prevents and Partially Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat  

Microsoft Academic Search

Background: Glucocorticoid-induced hypertension is associated with increased oxidative stress. The aim of the present study was to investigate the effects of aspirin, a potent antioxidant, on adrenocorticotropic hormone (ACTH) and dexamethasone (Dex)-induced hypertension.Methods: Male Sprague-Dawley (SD) rats were treated with saline, ACTH (0.2 mg\\/kg\\/d subcutaneously) or Dex (10 ?g\\/rat\\/d subcutaneously). Aspirin (100 mg\\/kg\\/d in drinking water) was given 4 days

Yi Zhang; Yuchun Miao; Judith A. Whitworth

2007-01-01

49

Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats  

Microsoft Academic Search

In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents fructose-induced hypertension by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether

S. Vasdev; V. Gill; S. Parai; L. Longerich; V. Gadag

2002-01-01

50

Quantitative ultrastructural study of the rat adrenal cortex in renal encapsulation-induced hypertension.  

PubMed Central

Hypertension was induced in young rats by latex encapsulation of both kidneys. By the fourth week, 85% of the renal-encapsulated (RE) rats became hypertensive. Varying degrees of cardiovascular involvement were evident in the moderately to severely hypertensive rats. The level of systolic blood pressure was directly correlated with the width and the volume of zona glomerulosa of the adrenal cortex. Electron microscopy combined with morphometric-stereologic techniques was employed to quantitate change in the adrenal cortex. The cells of both zona glomerulosa and zona fasciculata of RE rats showed significant increases in the volume of the cell, nucleus, smooth endoplasmic reticulum, and lipid droplets; only in the zona glomerulosa cells was the increase in surface area of the smooth endoplasmic reticulum statistically significant. It is suggested that these structural changes associated with renal-encapsulation hypertension are related at least in part to stress of the hypertensive cardiovascular disease. Images Figure 1 Figure 2 PMID:1247082

Kasemsri, S.; Nickerson, P. A.

1976-01-01

51

Drug induced intracranial hypertension associated with sulphasalazine treatment.  

PubMed

A 25-year-old female patient developed headache and papilledema under sulphasalazine treatment for ulcerative colitis. The patient met the International Headache Society's criteria for idiopathic intracranial hypertension. Sulphasalazine was discontinued and the patient was given azathioprine for ulcerative colitis and acetazolamide for intracranial hypertension. Three weeks later, her examination was normal and lumbar puncture revealed an opening pressure of 180-mm H(2)O. Sulphasalazine is a product of 5 aminosalicylate (5 ASA) and there seems to be a relationship between the administration of sulphasalazine and the onset of intracranial hypertension symptoms. Early diagnosis of intracranial hypertension is important in patients with ulcerative colitis receiving 5 ASA treatment to prevent visual complications. PMID:18070060

Sevgi, Eser; Yalcin, Gul; Kansu, Tulay; Varli, Kubilay

2008-02-01

52

Influence of antioxidants on blood-brain barrier permeability during adrenaline-induced hypertension.  

PubMed

We have examined the effect of antioxidants (vitamin E, and selenium) on the blood-brain barrier permeability during adreneline-induced acute hypertension in the female rats. The rats supplemented with nontoxic doses of sodium selenite in drinking water for three months or vitamin E was given intraperitoneally before adrenaline-induced acute hypertension. Evans-blue was used as a blood-brain barrier tracer. Mean values for Evans-blue dye were found to be 0.28 +/- 0.04 microg/g tissue in control animals and 1.0 +/- 0.2 microg tissue after adrenaline-induced acute hypertension (p < .01). Rats pretreated with selenium or vitamin E also showed macroscopic leakage of Evans-blue albumin after adrenaline injection i.e., there was no significant difference in protein extravasation between untreated and treated animals (p > .5). The mean value for Evans-blue dye was found to be 1.0 +/- 0.2 microg/g tissue in acute hypertension group, 0.9 +/- 0.2 microg/g tissue in selenium pretreated animals and 1.0 +/- 0.2 micrg/g tissue vitamin E injected animals after acute hypertension. The results show that antioxidants did not influence the blood-brain barrier breakdown during adrenaline-induced acute hypertension. PMID:11069044

Ozta?, B; Erkin, E; Dural, E; Isbir, T

2000-11-01

53

Apocynin but Not Allopurinol Prevents and Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat  

Microsoft Academic Search

Background: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension.Methods: Male Sprague-Dawley rats were divided into 10 groups of 10–20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol\\/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg\\/kg\\/day via food) were

Yi Zhang; Matthew M. K. Chan; Miles C. Andrews; Trevor A. Mori; Kevin D. Croft; Christopher G. Schyvens; Judith A. Whitworth

2005-01-01

54

Effects of ?-lipoic acid on deoxycorticosterone acetate–salt-induced hypertension in rats  

Microsoft Academic Search

We investigated the potential of natural occurring antioxidant ?-lipoic acid to prevent hypertension and hypertensive tissue injury induced by deoxycorticosterone acetate (DOCA) and salt in rats. Two weeks after the start of DOCA–salt treatment, the rats were given ?-lipoic acid (10 or 100 mg\\/kg\\/day, s.c.) or its vehicle for 2 weeks. Uninephrectomized rats without DOCA–salt treatment served as sham-operated controls.

Masanori Takaoka; Yutaka Kobayashi; Mikihiro Yuba; Mamoru Ohkita; Yasuo Matsumura

2001-01-01

55

Protective effects of estrogen on gender-specific development of diet-induced hypertension  

Microsoft Academic Search

Roberts, Christian K., Nosratola D. Vaziri, and R. James Barnard. Protective effects of estrogen on gender-specific development of diet-induced hypertension. J Appl Physiol 91: 2005-2009, 2001.—Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hor- mone status in the development and reversibility of hyper- tension. Normal

CHRISTIAN K. ROBERTS; NOSRATOLA D. VAZIRI; R. JAMES BARNARD

56

Phosphorylation-dependent PIH1D1 interactions define substrate specificity of the R2TP cochaperone complex.  

PubMed

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

2014-04-10

57

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

58

Prenatal dexamethasone 'programmes' hypotension, but stress-induced hypertension in adult offspring.  

PubMed

Low birth weight in humans is predictive of hypertension in adult life. Although the mechanisms underlying this link remain unknown, fetal overexposure to glucocorticoids has been implicated. We previously showed that prenatal dexamethasone (DEX) exposure in the rat lowers birth weight and programmes adult hypertension. The current study aimed to further investigate the nature of this hypertension and to elucidate its origins. Unlike previous studies, we assessed offspring blood pressure (BP) with radiotelemetry, which is unaffected by stress artefacts of measurement. We show that prenatal DEX during the last week of pregnancy results in offspring of low birth weight (14% reduction) that have lower basal BP in adulthood ( approximately 4-8 mmHg lower); with the commonly expected hypertensive phenotype only being noted when these offspring are subjected to even mild disturbance or a more severe stressor (up to 30 mmHg higher than controls). Moreover, DEX-treated offspring sustain their stress-induced hypertension for longer. Promotion of systemic catecholamine release (amphetamine) induced a significantly greater rise of BP in the DEX animals (77% increase) over that observed in the vehicle controls. Additionally, we demonstrate that the isolated mesenteric vasculature of DEX-treated offspring display greater sensitivity to noradrenaline and other vasoconstrictors. We therefore conclude that altered sympathetic responses mediate the stress-induced hypertension associated with prenatal DEX programming. PMID:18252958

O'Regan, David; Kenyon, Christopher J; Seckl, Jonathan R; Holmes, Megan C

2008-02-01

59

Pregnancy-induced hypertension is associated with altered anatomical patterns of Hyrtl's anastomosis.  

PubMed

Umbilical arteries carry the blood from the fetus to the placenta and are typically connected by Hyrtl's anastomosis, a connection that is located near where the umbilical cord meets the placenta. The investigation of the anastomosis in pathological conditions, including pregnancy-induced hypertension is limited. Hence, 200 placenta and umbilical cords, 100 from normotensive and 100 from pregnancy-induced hypertensive subjects, were dissected and measurements were recorded. A single anastomosis between the umbilical arteries was observed in 167 specimens. In 16 cases, the two umbilical arteries were fused, in 15 cases there was no anastomosis, and in two cases there was a single umbilical artery. In one specimen from a normotensive case, a double anastomosis was observed. To our knowledge this is only the second report of this rare anatomical variant. When an anastomosis is present, the connecting vessel can be transverse to or form an oblique angle with the umbilical arteries. We observed a striking increase in the number of artery pairs connected by a transverse vessel in specimens from hypertensive subjects relative to those from normotensive subjects. Moreover, placentas from hypertensive donors were small if the umbilical arteries were connected by an oblique anastomosis. In addition, the length of the anastomosis and its distance from the cord insertion was shorter in specimens from hypertensive compared to normotensive subjects. We conclude that pregnancy-induced hypertension alters the anatomy of Hyrtl's anastomosis, and in some circumstances, the placenta. PMID:24591344

Bhutia, Karma Lakhi; Sengupta, Ratnabali; Upreti, Benoy; Tamang, Binod K

2014-05-01

60

Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats  

PubMed Central

Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system. PMID:23860206

Kochi, Takahiro; Shimizu, Masahito; Ohno, Tomohiko; Baba, Atsushi; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

2013-01-01

61

Enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats.  

PubMed

Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system. PMID:23860206

Kochi, Takahiro; Shimizu, Masahito; Ohno, Tomohiko; Baba, Atsushi; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

2013-01-01

62

Bortezomib, a Proteasome Inhibitor, Attenuates Angiotensin II-Induced Hypertension and Aortic Remodeling in Rats  

PubMed Central

Background Hypertension is a highly prevalent disorder and a major risk factor for cardiovascular diseases. Hypertensive vascular remodeling is the pathological mal-adaption of blood vessels to the hypertensive condition that contributes to further development of high blood pressure and end-organ damage. Hypertensive remodeling involves, at least in part, changes in protein turnover. The ubiquitin proteasome system (UPS) is a major protein quality and quantity control system. This study tested the hypothesis that the proteasome inhibitor, bortezomib, would attenuate AngII-induced hypertension and its sequelae such as aortic remodeling in rats. Methodology/Principal Findings Male Sprague Dawley rats were subjected to AngII infusion for two weeks in the absence or presence of bortezomib. Mean arterial pressure was measured in conscious rats. Aortic tissue was collected for estimation of wall area, collagen deposition and expression of tissue inhibitors of matrix metalloproteases (TIMP), Ki67 (a marker of proliferation), reactive oxygen species (ROS) and VCAM-1 (a marker of inflammation). AngII infusion increased arterial pressure significantly (160±4 mmHg vs. vehicle treatment 133±2 mmHg). This hypertensive response was attenuated by bortezomib (138±5 mmHg). AngII hypertension was associated with significant increases in aortic wall to lumen ratio (?29%), collagen deposition (?14%) and expression of TIMP1 and TIMP2. AngII also increased MMP2 activity, proteasomal chymotrypsin-like activity, Ki67 staining, ROS generation and VCAM-1 immunoreactivity. Co-treatment of AngII-infused rats with bortezomib attenuated these AngII-induced responses. Conclusions Collectively, these data support the idea that proteasome activity contributes to AngII-induced hypertension and hypertensive aortic vascular remodeling at least in part by modulating TIMP1/2 and MMP2 function. Preliminary observations are consistent with a role for ROS, inflammatory and proliferative mechanisms in this effect. Further understanding of the mechanisms by which the proteasome is involved in hypertension and vascular structural remodeling may reveal novel targets for pharmacological treatment of hypertension, hypertensive remodeling or both. PMID:24205262

Li, Shuai; Wang, Xuejun; Li, Yifan; Kost, Curtis K.; Martin, Douglas S.

2013-01-01

63

Effect of losartan on oxidative stress-induced hypertension in Sprague-Dawley rats  

Microsoft Academic Search

BackgroundHypertension induced by oxidative stress has been demonstrated in normal rats. In the current study, we investigated the effect of the oral AT1 receptor blocker losartan (10 mmol\\/kg\\/day) on oxidative stress, induced by glutathione (GSH) depletion (using buthionine-sulfoximine, BSO, 30 mmol\\/L\\/day in the drinking water), in Sprague-Dawley rats.

Mohamed A. Bayorh; Agaba A. Ganafa; Robin R. Socci; Danita Eatman; Natalia Silvestrov; Imad K. Abukhalaf

2003-01-01

64

Differential Phenotypes of Tissue-Infiltrating T Cells during Angiotensin II-Induced Hypertension in Mice  

PubMed Central

Hypertension remains the leading risk factor for cardiovascular disease (CVD). Experimental hypertension is associated with increased T cell infiltration into blood pressure-controlling organs, such as the aorta and kidney; importantly in absence of T cells of the adaptive immune system, experimental hypertension is significantly blunted. However, the function and phenotype of these T cell infiltrates remains speculative and undefined in the setting of hypertension. The current study compared T cell-derived cytokine and reactive oxygen species (ROS) production from normotensive and hypertensive mice. Splenic, blood, aortic, kidney and brain T cells were isolated from C57BL/6J mice following 14-day vehicle or angiotensin (Ang) II (0.7 mg/kg/day, s.c.) infusion. T cell infiltration was increased in aorta, kidney and brain from hypertensive mice. Cytokine analysis in stimulated T cells indicated an overall Th1 pro-inflammatory phenotype, but a similar proportion (flow cytometry) and quantity (cytometric bead array) of IFN-?, TNF-?, IL-4 and IL-17 between vehicle- and Ang II- treated groups. Strikingly, elevated T cell-derived production of a chemokine, chemokine C-C motif ligand 2 (CCL2), was observed in aorta (?6-fold) and kidney in response to Ang II, but not in brain, spleen or blood. Moreover, T cell-derived ROS production in aorta was elevated ?3 -fold in Ang II-treated mice (n?=?7; P<0.05). Ang II-induced hypertension does not affect the overall T cell cytokine profile, but enhanced T cell-derived ROS production and/or leukocyte recruitment due to elevated CCL2, and this effect may be further amplified with increased infiltration of T cells. We have identified a potential hypertension-specific T cell phenotype that may represent a functional contribution of T cells to the development of hypertension, and likely several other associated vascular disorders. PMID:25501574

Wei, Zihui; Spizzo, Iresha; Diep, Henry; Drummond, Grant R.; Widdop, Robert E.; Vinh, Antony

2014-01-01

65

Resveratrol affects histone 3 lysine 27 methylation of vessels and blood biomarkers in DOCA salt-induced hypertension.  

PubMed

Hypertension is a risk factor for the cardiovascular diseases. Although, several drugs are used to treat hypertension, the success of the antihypertensive therapy is limited. Resveratrol decreases blood pressure in animal models of hypertension. This study researched the mechanisms behind the effects of resveratrol on hypertension. Hypertension was induced by using the deoxycorticosterone acetate (DOCA)-induced (15 mg/kg twice per week, subcutaneously) salt-sensitive hypertension model of Wistar rats. Hypertension caused a decrease in endothelium-dependent relaxations of the isolated thoracic aorta. Resveratrol treatment (50 mg/l in drinking water) prevented DOCA salt-induced hypertension, but did not improve endothelial dysfunction. Plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulfide (H2S) levels were not changed by DOCA salt application. However, treatment of resveratrol significantly decreased ADMA and increased TAC and H2S levels. NO level in circulation was not significantly changed by resveratrol. DOCA salt application and resveratrol treatment also caused an alteration in the epigenetic modification of vessels. Staining pattern of histone 3 lysine 27 methylation (H3K27me3) in the aorta and renal artery sections was changed. These results show that preventive effect of resveratrol on DOCA salt-induced hypertension might due to its action on the production of some blood biomarkers and the epigenetic modification of vessels that would focus upon new aspect of hypertension prevention and treatment. PMID:25234650

Han, Sevtap; Uludag, Mecit Orhan; Usanmaz, Suzan Emel; Ayaloglu-Butun, Fatma; Akcali, Kamil Can; Demirel-Yilmaz, Emine

2015-01-01

66

Antihypertensive effect of Silymarin on DOCA salt induced hypertension in unilateral nephrectomized rats  

Microsoft Academic Search

The objective of the present investigation was to evaluate the therapeutic efficacy of Silymarin in DOCA salt induced hypertension\\u000a in unilateral nephrectomized rats. Unilateral nephrectomy was performed in female Wistar rats (150–200 g). A week after unilateral\\u000a nephrectomy, hypertension was induced by DOCA (25 mg\\/kg, once a week; s.c; for 4 weeks) dispersed in cottonseed oil. The effect\\u000a of Silymarin (300 mg\\/kg and 500 mg\\/kg,

G. B. Jadhav; C. D. Upasani

67

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

PubMed

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

68

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

69

Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.  

PubMed

Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier. PMID:19812973

Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

2010-01-01

70

Digoxin Prevents Ouabain and High Salt Intake-Induced Hypertension in Rats With Sinoaortic Denervation  

Microsoft Academic Search

Digoxin prevents ouabain-induced hypertension in rats. In the present study, we tested whether this effect of digoxin depends on its sensitizing effect on baroreflex function or is due to an antagonistic action on exogenous ouabain or endogenous ouabainlike activity (\\

Bing S. Huang; Marian Kudlac; Raj Kumarathasan; Frans H. H. Leenen

71

Prenatal malnutrition-induced hypertension in young rats is prevented by neonatal capsaicin treatment  

Microsoft Academic Search

Prenatal malnutrition-induced fetal growth retardation in the rat results in elevated arterial blood pressure at adulthood. To test the contribution of cardiovascular sensory C fibers in the hypertensive state, arterial blood pressure was measured in prenatally undernourished rats treated at birth with capsaicin. The effects of the neonatal capsaicin treatment on heart rate and respiratory frequency were also evaluated. Maternal

Hernán Pérez; Samuel Ruiz; Rubén Soto-Moyano

2002-01-01

72

Role of glucocorticoids in programming of maternal diet-induced hypertension in the rat  

Microsoft Academic Search

A rat model of hypertension induced by in utero exposure to maternal low protein diets has previously been described. Low protein exposed rat pups are of lower weight at birth and have large associated placentas. Such animals are proposed, therefore, to mirror individuals in the human population perceived to be at greater risk of cardiovascular disease in adulthood. Recent work

Simon C. Langley-Evans; Gary J. Phillips; David S. Gardner; Alan A. Jackson

1996-01-01

73

Lisinopril attenuates renal oxidative injury in l -NAME-induced hypertensive rats  

Microsoft Academic Search

Hypertension and related oxidative stress are involved in the pathogenesis of any renal diseases. Angiotensin-converting enzyme\\u000a inhibitors have multi-directional renoprotective effects. In this study, we aimed to investigate whether lisinopril treatment\\u000a has any biochemical alterations on renal tissue in l-NAME (N?-nitro-l-arginine methyl ester) induced hypertension model. Twenty-eight Sprague–Dawley rats were included in this study and divided\\u000a into four equal groups

Faruk Öktem; Aynur Kirbas; Abdullah Armagan; Ayca Esra Kuybulu; H. Ramazan Yilmaz; Fehmi Özguner; Efkan Uz

2011-01-01

74

[Modern methods of early screening for preeclampsia and pregnancy-induced hypertension--a review].  

PubMed

Preeclampsia remains to be a serious perinatal complication and early screening for this disease to identify the high risk population before the first symptoms develop constitutes a considerable clinical challenge. Modern methods of screening for preeclampsia and pregnancy-induced hypertension include patients history biochemical serum markers and foetal DNA and RNA in maternal serum. They aid the process of developing an optimal protocol to initiate treatment in early pregnancy and to reduce the rate of complications. Our review presents an overview of the novel methods and techniques used for early screening for preeclampsia and pregnancy-induced hypertension. Most of the research focuses on 11-13 weeks of gestation due to the fact that the first prenatal examination is performed at that time. The most important information seems to be: weight, mass, mean blood pressure, history of pregnancy-induced hypertension or preeclampsia at previous pregnancies as well as the ethnic origin. During an ultrasound scan, pulsatility index of the uterine arteries is measured. Blood samples are obtained during the last part of the examination. At the moment only a few markers seem to be strong predictors of hypertensive disorders during pregnancy: pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Also, fetal DNA and RNA in maternal plasma are helpful in the prediction of preeclampsia as they are markers of the trophoblast apoptosis. Researchers aim at identifying the population at high risk of pregnancy-induced hypertension and preeclampsia in order to offer appropriate antenatal care to these women. At the moment many drugs and diet supplements are investigated to reduce the prevalence of hypertensive disorders in pregnancy. These medications are usually administrated in early gestation (up to 16 week of gestation) before the first clinical symptoms present. Low doses of aspirin were found to decrease the risk of preeclampsia in high-risk groups. Moreover, according to some recent research, also essential omega-3 fatty acids reduce the incidence of preeclampsia. None of the other investigated diet supplements or antioxidants were proven to successfully reduce incidents of hypertensive disorders. So far, there is available evidence on the lack of any effect for vitamines C, D or E. Further studies are necessary to define clinical useful markers of gestational hypertension. PMID:23342898

Poprawski, Grzegorz; Wender-Ozegowska, Ewa; Zawiejska, Agnieszka; Brazert, Jacek

2012-09-01

75

Effect of losartan on oxidative stress-induced hypertension in Sprague-Dawley rats  

Microsoft Academic Search

Hypertension induced by chronic oxidative stress has been demonstrated in normal rats and in situations of normal or low plasma angiotensin. In the current study, we investigated the effect of the AT1 receptor blocker losartan (LOS, 10 mmol\\/kg\\/day p.o.) on oxidative stress, induced by glutathione (GSH) depletion (using buthionine sulfoximine, BSO, 30 mmol\\/L\\/day in the drinking water), in Sprague-Dawley rats.

Mohamed A. Bayorh; Agaba A. Ganafa; Robin R. Socci; Danita E. Eatman; Imad Abukhalaf; Natalia Silvestrov; Nerimiah L. Emmett

2001-01-01

76

Influence of electroacupuncture on stress-induced hypertension and its mechanism  

Microsoft Academic Search

Background: Electroacupuncture (EA) and activation of the sympathetic inhibitory system in the brain, i.e. nucleus arcuatus–ventral periaqueductal gray matter–nucleus raphe obscurus (ARC–vPAG–NRO) system, can lower blood pressure (BP). This study was to observe the effect of EA on stressed-induced hypertensive rats and whether nitric oxide in vPAG can be involved in the effect of EA. Methods: On the anesthetized stress-induced

Li Li; Y. X Cao; H Xue; P Li; D. N Zhu

2002-01-01

77

Heme oxygenase-1 induces 15-lipoxygenase expression during hypoxia-induced pulmonary hypertension.  

PubMed

We previously reported that 15-lipoxygenase (15-LO) induced by hypoxia catalyzed the conversion of arachidonic acid (AA) into 15-hydroxyeicosatetraenoic acid (15-HETE), which plays an essential role in the development of hypoxic pulmonary arterial hypertension (HPH). However, the mechanisms by which hypoxia up-regulated 15-LO are still unclear. Heme oxygenase-1 (HO-1), an oxygen-dependent enzyme regulating vascular tone and cell proliferation, was implicated in HPH and was promoted by hypoxia. Therefore, the present study was carried out to determine whether hypoxia induced the expression of 15-LO via the HO-1 pathway. To test this hypothesis, we studied the role of HO-1 in HPH and 15-LO/15-HETE expression We found increased right ventricular systolic pressure and pulmonary arteries (PAs) reactivity to vasoconstrictors as well as intima-to-media ratio of PAs in HO-1 overexpressing transgenic mice. Moreover, HO-1 up-regulated 15-LO transcription and translation as well as 15-HETE in both transgenic mice and cultured pulmonary arterial smooth muscle cells (PASMCs). Results from immunoprecipitation and immunocytochemistry showed the interaction and colocalization of HO-1 and 15-LO. Together, these data suggest that HO-1 is an important upstream mediator in the hypoxia-induced 15-LO up-regulation during HPH. Unveiling the relevance of HO-1 signaling in PHP provides attractive treatment targets for HPH. PMID:23391748

Nie, Xiaowei; Hui, Yang; Shi, Shuai; Ma, Jun; Wang, Shuang; Qiu, Zhaoping; Song, Shasha; Pan, Zhenwei; Li, Qian; Gao, Xu; Zhu, Daling

2013-05-01

78

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

79

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

80

Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors.  

PubMed

Treatment of Wistar rats for 7 days with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, induces long-lasting hypertension associated with marked changes in vascular structure and reactivity and renin-angiotensin system activation. This study aimed at evaluating the role of oxidative stress in the development of DPSPX-induced hypertension and also at identifying the relative contribution of superoxide radical (O2.-) vs hydrogen peroxide (H2O2). Vascular and systemic prooxidant/antioxidant status was evaluated in sham (saline, i.p., 7 days) and DPSPX (90 microg/kg/h, i.p., 7 days)-treated rats. Systolic blood pressure was determined by invasive and non-invasive methods. The activity of vascular NADPH oxidase, superoxide dismutase (SOD), catalase and glutathione peroxidase was assayed by fluorometric/spectrophotometric methods. H2O2 levels were measured using an Amplex Red Hydrogen Peroxide kit. Plasma thiobarbituric acid reactive substances and plasma antioxidant capacity were also measured. In addition we tested the effects of antioxidants or inhibitors of reactive oxygen species generation on blood pressure, vascular hyperplasia and oxidative stress parameters. DPSPX-hypertensive rats showed increased activity of vascular NADPH oxidase, SOD, catalase and glutathione peroxidase, as well as increased H2O2 generation. DPSPX-hypertensive rats also had increased plasma lipid peroxidation and decreased plasma antioxidant capacity. Treatment with apocynin (1.5 mmol/l, per os, 14 days), or with polyethylene glycol (PEG)-catalase (10,000 U/kg/day, i.p., 8 days), prevented the DPSPX-induced effects on blood pressure, vascular structure and H2O2 levels. Tempol (3 mmol/l, per os, 14 days) failed to inhibit these changes, unless PEG-catalase was co-administered. It is concluded that O2.- generation with subsequent formation of H2O2 plays a major role in the development of DPSPX-induced hypertension. PMID:18519134

Sousa, Teresa; Pinho, Dora; Morato, Manuela; Marques-Lopes, José; Fernandes, Eduarda; Afonso, Joana; Oliveira, Sofia; Carvalho, Félix; Albino-Teixeira, António

2008-07-01

81

Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: Role of NADPH oxidase  

Microsoft Academic Search

Objective: Chronic administration of moderate amounts of red wine has been associated with a protective effect on the cardiovascular system. This study examined whether red wine polyphenols prevent the angiotensin II (Ang II)-induced hypertension and endothelial dysfunction in rats, and, if so, to elucidate the underlying mechanism. Methods: Hypertensive rats were obtained by a 14-day infusion of Ang II. Red

Mamadou Sarr; Marta Chataigneau; Sandrine Martins; Christa Schott; Jasser El Bedoui; Min-Ho Oak; Bernard Muller; Thierry Chataigneau; Valérie B. Schini-Kerth

2006-01-01

82

Loss of functional endothelial connexin40 results in exercise-induced hypertension in mice.  

PubMed

During activity, coordinated vasodilation of microcirculatory networks with upstream supply vessels increases blood flow to skeletal and cardiac muscles and reduces peripheral resistance. Endothelial dysfunction in humans attenuates activity-dependent vasodilation, resulting in exercise-induced hypertension in otherwise normotensive individuals. Underpinning activity-dependent hyperemia is an ascending vasodilation in which the endothelial gap junction protein, connexin (Cx)40, plays an essential role. Because exercise-induced hypertension is proposed as a forerunner to clinical hypertension, we hypothesized that endothelial disruption of Cx40 function in mice may create an animal model of this condition. To this end, we created mice in which a mutant Cx40T152A was expressed alongside wildtype Cx40 selectively in the endothelium. Expression of the Cx40T152A transgene in Xenopus oocytes and mouse coronary endothelial cells in vitro impaired both electric and chemical conductance and acted as a dominant-negative against wildtype Cx40, Cx43, and Cx45, but not Cx37. Endothelial expression of Cx40T152A in Cx40T152ATg mice attenuated ascending vasodilation, without effect on radial coupling through myoendothelial gap junctions. Using radiotelemetry, Cx40T152ATg mice showed an activity-dependent increase in blood pressure, which was significantly greater than in wildtype mice, but significantly less than in chronically hypertensive, Cx40knockout mice. The increase in heart rate with activity was also greater than in wildtype or Cx40knockout mice. We conclude that the endothelial Cx40T152A mutation attenuates activity-dependent vasodilation, producing a model of exercise-induced hypertension. These data highlight the importance of endothelial coupling through Cx40 in regulating blood pressure during activity. PMID:25547341

Morton, Susan K; Chaston, Daniel J; Howitt, Lauren; Heisler, Jillian; Nicholson, Bruce J; Fairweather, Stephen; Bröer, Stefan; Ashton, Anthony W; Matthaei, Klaus I; Hill, Caryl E

2015-03-01

83

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

PubMed Central

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

2013-01-01

84

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

85

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

86

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

PubMed

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; White, Ed

2011-06-01

87

Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in l-NAME induced hypertensive rats  

Microsoft Academic Search

The present study was undertaken to assess the antihypertensive and antioxidant effects of veratric acid on N?-nitro-L arginine methyl ester (l-NAME) induced hypertensive rats. Hypertension was induced in adult male albino rats of the Wistar strain, weighing 180–220g, by oral administration of the l-NAME (40mg\\/kg body weight\\/day) in drinking water for 4weeks. Rats were treated with various doses of veratric

Murugesan Saravanakumar; Boobalan Raja

2011-01-01

88

Reduced uterine perfusion pressure induces hypertension in the pregnant mouse.  

PubMed

Despite preeclampsia being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for its pathogenesis have yet to be fully elucidated. Growing evidence indicates that reduced uteroplacental perfusion and the resulting placental ischemia triggers the cascade of events leading to this maternal disorder. While the well-established rat model of reduced uterine perfusion pressure (RUPP) is providing invaluable insight into the etiology of preeclampsia, the aim of this study was to develop a mouse model of reduced uterine perfusion to expand mechanistic investigation by incorporation with novel gene-targeted mice. To accomplish this aim, a sham surgical procedure or a restriction of blood flow at the abdominal aorta and the ovarian arteries was initiated at day 13 of gestation in C57BL/6J mice. Mean arterial pressure measured in conscious, chronically instrumented mice was significantly elevated in the RUPP (120 ± 4 mmHg) compared with the sham (104 ± 4 mmHg) mice at day 18 of gestation (P < 0.01). Placental ischemia reduced fetal weights (0.95 ± 0.04 and 0.80 ± 0.02 g; RUPP vs. Sham, respectively; P < 0.02) and increased circulating levels of antiangiogenic soluble fms-related tyrosine kinases (sFlt)-1 (P < 0.05) in the RUPP at day 18 of gestation. Plasma concentrations of sFlt-1 are increased in preeclamptic patients and in response to reduced uterine perfusion in the rat. Thus, these results suggest that the mouse model of reduced uterine perfusion is applicable to facilitate novel mechanistic investigation into the etiology of hypertension that results from placental ischemia during pregnancy. PMID:25298513

Intapad, Suttira; Warrington, Junie P; Spradley, Frank T; Palei, Ana C; Drummond, Heather A; Ryan, Michael J; Granger, Joey P; Alexander, Barbara T

2014-12-01

89

Renin System of the Kidney in ISIAH Rats with Inherited Stress-Induced Arterial Hypertension  

Microsoft Academic Search

The renal renin system was studied in ISIAH rats with inherited stress-induced arterial hypertension. The expression of genes\\u000a for renin (Ren1) and cyclooxygenase (Cox-2) was evaluated in renal tissue of ISIAH and WAG rats (normotensive control). Basal\\u000a gene expression for Ren1 and Cox-2 in ISIAH rats was much lower than in WAG rats. Water deprivation for 11 h was followed

L. A. Fedoseeva; G. M. Dymshits; A. L. Markel; G. S. Jakobson

2009-01-01

90

Effects of Sepiapterin Supplementation and NOS Inhibition on Glucocorticoid-Induced Hypertension  

Microsoft Academic Search

BackgroundGlucocorticoid-induced hypertension is associated with imbalance between nitric oxide (NO) and superoxide. One of the pathways that causes this imbalance is endothelial NO synthase (eNOS) uncoupling. In the present study, adrenocorticotrophic hormone (ACTH)- and dexamethasone-treated rats were further treated with sepiapterin, a precursor of tetrahydrobiopterin, or N-nitro-L-arginine (NOLA), an inhibitor of NOS, to investigate the role of eNOS uncoupling in

Mya Thida; John Earl; Yan Zhao; Hans Wang; Chi S. Tse; Janine J. Vickers; Matthew Sutton; Sharon L. H. Ong; Trevor A. Mori; Kevin D. Croft; Judith A. Whitworth; Yi Zhang

2010-01-01

91

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

92

Renal Angiotensin-converting enzyme is essential for the hypertension induced by nitric oxide synthesis inhibition.  

PubMed

The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na(+)/H(+) exchanger 3, Na(+)/Pi co-transporter 2, phosphorylated Na(+)/K(+)/Cl(-) cotransporter, and phosphorylated Na(+)/Cl(-) cotransporter; and greater reductions in abundance and processing of the ? isoform of the epithelial Na(+) channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition. PMID:25012170

Giani, Jorge F; Janjulia, Tea; Kamat, Nikhil; Seth, Dale M; Blackwell, Wendell-Lamar B; Shah, Kandarp H; Shen, Xiao Z; Fuchs, Sebastien; Delpire, Eric; Toblli, Jorge E; Bernstein, Kenneth E; McDonough, Alicia A; Gonzalez-Villalobos, Romer A

2014-12-01

93

Sodium thiosulfate attenuates angiotensin II-induced hypertension, proteinuria and renal damage.  

PubMed

Hypertension and proteinuria are important mediators of renal damage. Despite therapeutic interventions, the number of patients with end stage renal disease steadily increases. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with vasodilatory, anti-inflammatory and antioxidant properties. These beneficial characteristics make H2S an attractive candidate for pharmacological use in hypertensive renal disease. We investigated the protective properties of H2S in angiotensin II (Ang II)-induced hypertensive renal disease in rats. Treatment with the H2S donor NaHS and major H2S metabolite sodium thiosulfate (STS) during three weeks of Ang II infusion reduced hypertension, proteinuria, oxidative stress and renal functional and structural deterioration. In an ex vivo isolated perfused kidney setup, NaHS, but not STS, reduced intrarenal pressure. The effect of NaHS could partially be explained by its activation of the ATP-sensitive potassium channels. In conclusion, treatment with H2S attenuates Ang II-associated functional and structural renal deterioration, suggesting that intervention in H2S production pathways has potential therapeutic benefit and might be a valuable addition to the already existing antihypertensive and renoprotective therapies. PMID:25459997

Snijder, Pauline M; Frenay, Anne-Roos S; Koning, Anne M; Bachtler, Matthias; Pasch, Andreas; Kwakernaak, Arjan J; van den Berg, Else; Bos, Eelke M; Hillebrands, Jan-Luuk; Navis, Gerjan; Leuvenink, Henri G D; van Goor, Harry

2014-11-15

94

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

95

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

96

Lisinopril attenuates renal oxidative injury in L-NAME-induced hypertensive rats.  

PubMed

Hypertension and related oxidative stress are involved in the pathogenesis of any renal diseases. Angiotensin-converting enzyme inhibitors have multi-directional renoprotective effects. In this study, we aimed to investigate whether lisinopril treatment has any biochemical alterations on renal tissue in L-NAME (N?-nitro-L-arginine methyl ester) induced hypertension model. Twenty-eight Sprague-Dawley rats were included in this study and divided into four equal groups (n = 7): control group, L-NAME treated group (75 mg/kg/day), L-NAME plus lisinopril treated group and only lisinopril treated group (10 mg/kg/day). L-NAME and lisinopril were continued for 6 weeks. Systolic blood pressures were measured by using tail cuff method. In biochemical analysis, malondialdehyde (MDA, an index of lipid peroxidation) levels, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissues were used as markers of oxidative stress-induced renal impairment. Microalbumin and N-acetyl-?-D-glucosaminidase (NAG) in urine were determined as markers of renal tubular damage related to hypertension. Chronic L-NAME administration resulted in a significant depletion of serum nitric oxide (NO). When compared with control group, serum creatinine, microalbumin, urine NAG, renal tissue MDA level, and CAT activities were significantly high, while renal tissue SOD and GSH-Px activities low in L-NAME group. In the L-NAME plus lisinopril treated group, serum creatinine, microalbumin and urine NAG, renal MDA level and CAT activity decreased, whereas SOD, GSH-Px activities in renal tissue and serum NO levels were increased. Thus, lisinopril treatment reversed these effects. There were not any significant difference between L-NAME plus lisinopril treated group and control group concerning serum creatinine, renal tissue MDA level and SOD, GSH-Px, CAT activities. These results suggest that lisinopril could diminish biochemical alterations in L: -NAME induced hypertensive renal damage that occurs by oxidative stress. PMID:21479940

Oktem, Faruk; Kirbas, Aynur; Armagan, Abdullah; Kuybulu, Ayca Esra; Yilmaz, H Ramazan; Ozguner, Fehmi; Uz, Efkan

2011-06-01

97

Tetrahydrocurcumin Protects against Cadmium-Induced Hypertension, Raised Arterial Stiffness and Vascular Remodeling in Mice  

PubMed Central

Background Cadmium (Cd) is a nonessential heavy metal, causing oxidative damage to various tissues and associated with hypertension. Tetrahydrocurcumin (THU), a major metabolite of curcumin, has been demonstrated to be an antioxidant, anti-diabetic, anti-hypertensive and anti-inflammatory agent. In this study, we investigated the protective effect of THU against Cd-induced hypertension, raised arterial stiffness and vascular remodeling in mice. Methods Male ICR mice received CdCl2 (100 mg/l) via drinking water for 8 weeks. THU was administered intragastrically at dose of 50 or 100 mg/kg/day concurrently with Cd treatment. Results Administration of CdCl2 significantly increased arterial blood pressure, blunted vascular responses to vasoactive agents, increased aortic stiffness, and induced hypertrophic aortic wall remodeling by increasing number of smooth muscle cells and collagen deposition, decreasing elastin, and increasing matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aortic medial wall. Supplementation with THU significantly decreased blood pressure, improved vascular responsiveness, and reversed the structural and mechanical alterations of the aortas, including collagen and elastin deposition. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated oxidative stress and enhanced antioxidant glutathione. Moreover, THU also reduced the accumulation of Cd in the blood and tissues. Conclusions Our results suggest that THU ameliorates cadmium-induced hypertension, vascular dysfunction, and arterial stiffness in mice through enhancing NO bioavailability, attenuating oxidative stress, improving vascular remodeling and decreasing Cd accumulation in other tissues. THU has a beneficial effect in moderating the vascular alterations associated with Cd exposure. PMID:25502771

Sangartit, Weerapon; Kukongviriyapan, Upa; Donpunha, Wanida; Pakdeechote, Poungrat; Kukongviriyapan, Veerapol; Surawattanawan, Praphassorn; Greenwald, Stephen E.

2014-01-01

98

Effects of tetrahydrobiopterin oral treatment in hypoxia-induced pulmonary hypertension in rat  

PubMed Central

Abstract Endothelial nitric oxide synthase (eNOS) plays a major role in maintaining pulmonary vascular homeostasis. Tetrahydrobiopterin (BH4), an essential cofactor that stabilizes the dimerization of eNOS and balances nitric oxide (NO) and superoxide production, may have therapeutic potential in pulmonary hypertension. In the isolated perfused lung, we demonstrated a direct effect of exogenous administration of BH4 on pulmonary NO production, leading to acute vasorelaxation during the plateau phase of hypoxia-induced pulmonary vasoconstriction. In the chronic hypoxia-induced pulmonary hypertension rat model, chronic BH4 oral administration attenuated the pressor response to hypoxia (mean pulmonary artery pressure ± standard error of the mean, 31.8 ± 0.5 mmHg at 100 mg/kg/day; placebo group, 36.3 ± 0.6 mmHg; P < 0.05). During telemetric monitoring, right ventricular systolic pressure was reduced by approximately 50% after 1 week of BH4 treatment at 100 mg/kg/day. BH4 at 100 mg/kg/day reduced right ventricular hypertrophy (from 0.55 ± 0.01 to 0.50 ± 0.01; P < 0.05) and pulmonary vascular muscularization (from 79.2% ± 2% to 65.2% ± 3%; P < 0.01). BH4 treatment enhanced lung eNOS activity and reduced superoxide production, with a net increase in cyclic guanosine monophosphate levels. BH4 is effective in attenuating pulmonary hypertension in the hypoxic rat model when given as a rescue therapy.

Francis, Bahaa N.; Hale, Ashley; Channon, Keith M.; Wilkins, Martin R.

2014-01-01

99

Modulatory effect of sesamol on DOCA-salt-induced oxidative stress in uninephrectomized hypertensive rats.  

PubMed

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180-200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects. PMID:23576423

Hemalatha, Govindasamy; Pugalendi, Kodukkur Viswanathan; Saravanan, Ramalingam

2013-07-01

100

Renin system of the kidney in ISIAH rats with inherited stress-induced arterial hypertension.  

PubMed

The renal renin system was studied in ISIAH rats with inherited stress-induced arterial hypertension. The expression of genes for renin (Ren1) and cyclooxygenase (Cox-2) was evaluated in renal tissue of ISIAH and WAG rats (normotensive control). Basal gene expression for Ren1 and Cox-2 in ISIAH rats was much lower than in WAG rats. Water deprivation for 11 h was followed by a 4-fold increase in Cox-2 gene expression in ISIAH rats. The increase in gene expression was insignificant in WAG rats (by 30%). Renin gene expression in renal tissue of ISIAH and WAG rats remained practically unchanged after water deprivation. We conclude that a change in Cox-2 gene expression after short-term water deprivation serves as a reliable criterion for functional strain of the renal renin system in hypertensive ISIAH rats. PMID:19513415

Fedoseeva, L A; Dymshits, G M; Markel, A L; Jakobson, G S

2009-02-01

101

Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension  

PubMed Central

Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca2+ handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca2+ transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca2+-ATPase activity, increased sarcoplasmic reticular Ca2+-release fraction, and increased Ca2+ spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca2+ handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs. PMID:22427523

Benoist, David; Stones, Rachel; Drinkhill, Mark J.; Benson, Alan P.; Yang, Zhaokang; Cassan, Cecile; Gilbert, Stephen H.; Saint, David A.; Cazorla, Olivier; Steele, Derek S.; Bernus, Olivier

2012-01-01

102

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II.  

PubMed

Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the hypothesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg(-1)·min(-1) for 14 days significantly (P < 0.05) elevated blood pressure compared with sham-operated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [+1,173 ± 212 arbitrary units (AU) and +35 ± 5 mmHg, n = 10] compared with sham normotensive rats (+419 ± 103 AU and +13 ± 2 mmHg, n = 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats (n = 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91(phox), a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex. PMID:23086992

Koba, Satoshi; Watanabe, Ryosuke; Kano, Naoko; Watanabe, Tatsuo

2013-01-01

103

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

104

Angiotensin-II Induced Hypertension and Renovascular Remodeling in TIMP2 Knockout Mice  

PubMed Central

Sustained hypertension induces renovascular remodeling by altering extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) are Zn-dependent enzymes that regulate ECM turnover in concert with their inhibitors, tissue inhibitors of metalloproteinases, TIMPs. Increased MMP-2 & -9 have been implicated in hypertensive complications; however, the contribution of individual MMPs/TIMPs in renal remodeling has not been fully elucidated. The purpose of this study was to determine the effect of TIMP2 deficiency and thus MMP-2 on Ang-II induced renal remodeling. C57BL/6J (WT) and TIMP2 knockout mice were infused with Angiotensin-II (Ang-II) at 250 ng. kg-1. min-1 for 4 weeks. Blood pressure was measured weekly and end-point laser Doppler flowmetry was done to assess cortical blood flow. Immunohistochemical staining was performed for collagen and elastin analyses. The activity of MMP-9, and -2 was determined by Gelatin zymography. Ang-II induced similar elevation in mean blood pressure in TIMP2-/- and WT mice. In TIMP2-/- mice, Ang-II treatment was associated with a greater reduction in renal cortical blood flow and barium angiography demonstrated decreased vascular density compared to Ang-II treated WT mice. Peri-glomerular and vascular collagen deposition was increased and elastin content was decreased causing increased wall-to-lumen ratio in TIMP2-/- mice compared to WT mice receiving Ang-II. Ang-II increased the expression and activity of MMP-9 predominantly in TIMP2-/- mice than in WT mice. These results suggest that TIMP2 deficiency exacerbates renovascular remodeling in agonist induced hypertension by a mechanism which may, in part, be attributed to increased activity of MMP-9. PMID:24077247

PUSHPAKUMAR, Sathnur; KUNDU, Sourav; PRYOR, Tyranny; GIVVIMANI, Srikanth; LEDERER, Eleanor; TYAGI, Suresh C.; SEN, Utpal

2014-01-01

105

Selective Inactivation of PTEN in Smooth Muscle Cells Synergizes With Hypoxia to Induce Severe Pulmonary Hypertension  

PubMed Central

Background Pulmonary vascular remodeling in pulmonary hypertension (PH) is characterized by increased vascular smooth muscle cell (SMC) and adventitial fibroblast proliferation, small vessel occlusion, and inflammatory cell accumulation. The underlying molecular mechanisms driving progression remain poorly defined. We have focused on loss of the phosphatase PTEN in SMCs as a major driver of pathological vascular remodeling. Our goal was to define the role of PTEN in human PH and in hypoxia?induced PH using a mouse model with inducible deletion of PTEN in SMCs. Methods and Results Staining of human biopsies demonstrated enhanced inactive PTEN selectively in the media from hypertensive patients compared to controls. Mice with induced deletion of PTEN in SMCs were exposed to normoxia or hypoxia for up to 4 weeks. Under normoxia, SMC PTEN depletion was sufficient to induce features of PH similar to those observed in wild?type mice exposed to chronic hypoxia. Under hypoxia, PTEN depletion promoted an irreversible progression of PH characterized by increased pressure, extensive pulmonary vascular remodeling, formation of complex vascular lesions, and increased macrophage accumulation associated with synergistic increases in proinflammatory cytokines and proliferation of both SMCs and nonSMCs. Conclusions Chronic inactivation of PTEN selectively in SMC represents a critical mediator of PH progression, leading to cell autonomous events and increased production of factors correlated to proliferation and recruitment of adventitial and inflammatory cells, resulting in irreversible progression of the disease. PMID:23727701

Horita, Henrick; Furgeson, Seth B.; Ostriker, Allison; Olszewski, Kyle A.; Sullivan, Timothy; Villegas, Leah R.; Levine, Michelle; Parr, Jane E.; Cool, Carlyne D.; Nemenoff, Raphael A.; Weiser?Evans, Mary C. M.

2013-01-01

106

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF  

Microsoft Academic Search

This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan

Hisato Nako; Keiichiro Kataoka; Nobutaka Koibuchi; Yi-Fei Dong; Kensuke Toyama; Eiichiro Yamamoto; Osamu Yasuda; Hidenori Ichijo; Hisao Ogawa; Shokei Kim-Mitsuyama

2012-01-01

107

Does copper enhance the antihypertensive effect of Elaeocarpus ganitrus in experimentally induced hypertensive rats?  

PubMed Central

Ayurveda, one of the traditional systems of medicine of India, reports that the seeds of Elaeocarpus ganitrus Linn. (Tilaceae) can be used for the treatment of hypertension. The main aim is to evaluate the antihypertensive effect of Elaeocarpus ganitrus (Rudraksha) seeds. Powdered seeds were extracted by maceration, overnight, using water, in copper (E1) and glass vessel (E2) and analyzed for antihypertensive activity in cadmium chloride (1 mg/kg intraperitoneally, for a period of 15 days) induced hypertensive male Wistar rats at three dose levels. E1 was administered at the dose of 5, 10, and 15 mg/kg and E2 at dose of 10, 20, and 30 mg/kg. All the data were analyzed using one way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. E1 and E2 did not show any toxicity at the dose of 5 g/kg in rats. It was found that 15 mg/kg of E1 and 30 mg/kg of E2 decreases the blood pressure by 30.20 mmHg and 28.96 mmHg, respectively, in hypertensive rats. Thus, it can be said that 15 mg/kg of E1 produced similar decrease in blood pressure as was observed with 30 mg/kg of E2. Copper ions in E1 might be additively affecting the reduction in blood pressure with the usage of Elaeocarpus ganitrus extracts. PMID:24948856

Barve, Kalyani H; Chodankar, Rahul

2014-01-01

108

Syringic acid ameliorates (L)-NAME-induced hypertension by reducing oxidative stress.  

PubMed

The objective of the present study was to investigate the effects of syringic acid (SA), a phenolic acid, on N(?)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats by oral administration of L-NAME (40 mg/kg/day) dissolved in drinking water daily for 4 weeks. Rats were treated with different doses of SA (25, 50, and 100 mg/kg body weight (b.w.)). Systolic blood pressure of control and experimental rats was recorded. Plasma nitric oxide metabolites (NOx), lipid peroxidative products such as thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione were estimated in erythrocytes, plasma, and tissues of experimental rats. Hepatic marker enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and renal functional markers such as urea, uric acid, and creatinine were also estimated in serum. The increased levels of blood pressure, lipid peroxidation products, hepatic and renal function markers, and the decreased level of NOx and antioxidants in L-NAME-induced hypertensive rats were reversed upon SA treatment. The protective effect at the dose of the three tested doses (25, 50, and 100 mg/kg) of SA at a dose of 50 mg/kg b.w. exerts optimum protection. Biochemical findings are substantiated by the histological observation. The protective effects of SA are mediated by reducing oxidative stress and retaining the bioavailability of NO in the cardiovascular system. PMID:23079793

Kumar, Subramanian; Prahalathan, Pichavaram; Raja, Boobalan

2012-12-01

109

Hypertension-induced cerebral atherosclerosis in the cholesterol-fed rabbit.  

PubMed

Foam cell lesions were found in cholesterol-fed rabbits with induced hypertension, particularly in intimal cushions at branching sites, where permeability to horseradish peroxidase was enhanced. Permeability to horseradish peroxidase was enhanced at the edge of intimal cushions without foam cell accumulation. This finding suggests that permeability is increased before foam cell infiltration. No foam cell lesions were observed in the intima of cerebral arteries distant from branching sites, but insudation of plasma constituents here caused endothelial cells to separate from the subendothelial matrices. Foam cell lesions were absent from the cerebral arteries in normotensive cholesterol-fed rabbits. PMID:678315

Kurozumi, T; Tanaka, K; Yae, Y

1978-06-01

110

Diesel exhaust induced pulmonary and cardiovascular impairment: The role of hypertension intervention  

SciTech Connect

Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or L-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500 ?g/m{sup 3}), 4 h/day for 2 days or 5 days/week for 4 weeks. Acute and 4-week gas and DE exposures increased neutrophils and ?-glutamyl transferase (?-GT) activity in lavage fluid of WKY and SH rats. DE (4 weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-?, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while L-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF ?-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by L-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-?, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers. - Highlights: ? Acute diesel exhaust exposure induces pulmonary inflammation in healthy rats. ? In hypertensive rats diesel exhaust effects are seen only after long term exposure. ? Normalizing blood pressure reverses lung protein leakage caused by diesel exhaust. ? Normalizing blood pressure reverses atherogenic effects of diesel exhaust. ? Diesel exhaust and hydralazine cause similar aorta effect on vascular tone markers.

Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Thomas, Ronald F.; Ledbetter, Allen D.; Schladweiler, Mette C.; Bass, Virginia; Krantz, Q. Todd; King, Charly [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Nyska, Abraham [Tel Aviv University, Tel Aviv (Israel); Richards, Judy E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States); Andrews, Debora [Research Core Unit, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC 27711 (United States); Gilmour, M. Ian [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development (ORD), U.S. Environmental Protection Agency - EPA, Research Triangle Park, NC 27711 (United States)

2013-04-15

111

Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats.  

PubMed

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

112

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

113

Effects of melatonin on blood pressure in stress-induced hypertension in rats.  

PubMed

Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM. PMID:18637016

Xia, Chun-Mei; Shao, Ci-Hui; Xin, Lin; Wang, Yang-Rong; Ding, Chao-Nan; Wang, Jin; Shen, Lin-Lin; Li, Li; Cao, Yin-Xiang; Zhu, Da-Nian

2008-10-01

114

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

115

Aldosterone acting through the central nervous system sensitizes angiotensin II-induced hypertension.  

PubMed

Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system. PMID:22949534

Xue, Baojian; Zhang, Zhongming; Roncari, Camila F; Guo, Fang; Johnson, Alan Kim

2012-10-01

116

Airway resistance, inflammation and oxidative stress following exposure to diesel exhaust particle in angiotensin II-induced hypertension in mice.  

PubMed

Exposure to particulate matter is a risk factor for respiratory and cardiovascular diseases. However, the mechanisms underlying these effects are not well understood. Here, we compared the impact of diesel exhaust particles (DEP) on airway resistance, inflammation and oxidative stress in normal mice, or mice made hypertensive by implanting osmotic minipump infusing angiotensin II. On day 13 after the onset of infusion, angiotensin II induced significant increase in heart rate (P<0.05) and systolic blood pressure (P<0.0001). On the same day, mice were intratracheally instilled with either DEP (15 ?g/mouse) or saline. Twenty-four hour later, the measurement of airway reactivity to methacholine (0-10mg/ml) in vivo by a forced oscillation technique showed a significant and dose dependent increase in airway resistance in normotensive mice exposed to DEP compared to those exposed to saline. In hypertensive mice, there was no difference in airway resistance in DEP versus saline exposed mice. However, following exposure to DEP, airway resistance significantly increased in normotensive versus hypertensive mice. Bronchoalveolar lavage (BAL) fluid analysis showed a significant increase in macrophage numbers in normotensive mice exposed to DEP compared to those exposed to saline, and to hypertensive mice exposed to DEP. Neutrophil numbers were significantly increased in both normotensive and hypertensive mice exposed to DEP compared with their respective control groups. Superoxide dismutase activity was significantly decreased following DEP exposure in both normotensive and hypertensive mice compared to their respective controls. However, total proteins, a marker for increase of epithelial permeability, and malondialdehyde, a reflection of lipid peroxidation, were only increased in normotensive mice exposed to DEP. Therefore, our data suggest that DEP do not aggravate airway resistance and inflammation in angiotensin II-induced hypertensive mice. On the contrary, at the dose of DEP and time point investigated, airway resistance, inflammation and oxidative stress are increased in normotensive compared to hypertensive mice. PMID:22214961

Nemmar, Abderrahim; Subramaniyan, Deepa; Zia, Shaheen; Yasin, Javed; Ali, Badreldin H

2012-02-26

117

Strain-dependent differences of restraint stress-induced hypertension in WKY and SHR.  

PubMed

The aim of our study was to investigate differences in restraint stress-response between normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) and the consequences for tail-cuff (TC) blood pressure measurements. We therefore radiotelemetrically collected cardiovascular data from WKY and SHR that underwent TC procedures and measured plasma norepinephrine (NE) and angiotensin II (ATII) levels as well as gene expression of the adrenal and hypothalamic tyrosine-hydroxylase, the rate-limiting enzyme in NE synthesis. Furthermore, we determined the effects of antihypertensive therapy using the beta(1)-receptor antagonist metoprolol, the alpha(1)-receptor antagonist doxazosin and the AT(1)-receptor antagonist telmisartan as mono- or combination therapies during the TC procedure. Results show that the TC procedure induced a stress reaction characterised by greatly increasing heart rate (HR) and blood pressure (BP) and elevating plasma norepinephrine and angiotensin II concentrations. Strain-dependent differences were found concerning stress reactions during rest (more pronounced effects) and activity of the two rat strains. In both strains, metoprolol inhibited the TC-induced increase in HR and doxazosin the TC-induced increase in BP. Telmisartan, in addition, reduced hypertension in SHR, slightly reduced the TC-induced increase of BP in SHR but had no effect in WKY. The cardiovascular data as well as those on NE, ATII and TH expression clearly show that SHR are less able to cope with stress-related mechanisms than the normotensive WKY. Since TC activates both the sympathetic as well as renin-angiotensin system this method is not appropriate to evaluate neither physiological nor drug-induced effects on BP and HR. PMID:19268675

Grundt, Alexander; Grundt, Christina; Gorbey, Stefan; Thomas, Martin A; Lemmer, Björn

2009-06-22

118

Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension  

SciTech Connect

Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible radioactivity was detected in urine; this fact infers that under physiological circumstances, urinary DHETs largely derive from the kidney. That P450 metabolites of arachidonic acid are formed in humans supports the hypothesis that these metabolites contribute to the physiological response to normal pregnancy and the pathophysiology of pregnancy-induced hypertension.

Catella, F.; Lawson, J.A.; Fitzgerald, D.J.; FitzGerald, G.A. (Vanderbilt Univ., Nashville, TN (USA))

1990-08-01

119

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

120

Taurine attenuates hypertension and renal dysfunction induced by cyclosporine A in rats.  

PubMed

Cyclosporine A (CsA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA-induced hypertension and nephrotoxicity. Taurine, the major intracellular free beta-amino acid, is known to be an endogenous anti-oxidant and membrane-stabilizing agent. The present study was designed to investigate the effects of taurine on CsA-induced oxidative stress, hypertension and renal dysfunction. 2. Animals were assigned into four groups of seven rats each as follows: (i) control group, receiving vehicle (olive oil; 1 mL/kg, s.c.); (ii) CsA group, given CsA (25 mg/kg per day, s.c.) for 21 days; (iii) taurine group, supplemented with taurine (1% in the drinking water); and (iv) taurine + CsA group, treated with taurine 3 days before and concurrently during CsA injections for 21 days. 3. Cyclosporine A administration elevated blood pressure, reduced serum nitric oxide (NO) levels and deteriorated renal function, as assessed by increased serum creatinine levels and proteinuria and reduced urine flow rate and creatinine clearance compared with vehicle-treated rats. Cyclosporine A induced oxidative stress, as indicated by increased renal tissue concentrations of thiobarbituric acid-reactive substances and reduced concentrations of renal glutathione, glutathione peroxidase and superoxide dismutase. Conversely, no change was noted in renal catalase activity. Moreover, the kidneys of CsA-treated rats showed interstitial inflammation and renal tubular atrophy. 4. Taurine markedly reduced elevated blood pressure, attenuated renal dysfunction and the reduction in serum NO levels and counteracted the deleterious effects of CsA on oxidative stress markers. Furthermore, taurine ameliorated CsA-induced morphological changes. 5. These data clearly indicate the protective potential of taurine against CsA-induced hypertension and nephrotoxicity and suggest a significant contribution of its anti-oxidant property to this beneficial effect. PMID:16487261

Hagar, Hanan H; El Etter, Eman; Arafa, Maha

2006-03-01

121

Hemodynamic basis for the limited renal injury in rats with angiotensin II-induced hypertension.  

PubMed

ANG II is thought to increase the susceptibility to hypertension-induced renal disease (HIRD) via blood pressure (BP)-dependent and BP-independent pathways; however, the quantitative relationships between BP and HIRD have not been examined in ANG II-infused hypertensive rats. We compared the relationship between radiotelemetrically measured BP and HIRD in Sprague-Dawley rats (Harlan) chronically administered ANG II (300-500 ng·kg(-1)·min(-1), n = 19) for 4 wk versus another commonly employed pharmacological model of hypertension induced by the chronic administration of N(?)-nitro-l-arginine methyl ester (l-NAME, 50 mg·kg(-1)·min(-1), n = 23). Despite the significantly higher average systolic BP associated with ANG II (191.1 ± 3.2 mmHg) versus l-NAME (179.9 ± 2.5 mmHg) administration, the level of HIRD was very modest in the ANG II versus l-NAME model as evidenced by significantly less glomerular injury (6.6 ± 1.3% vs. 11.3 ± 1.5%, respectively), tubulointerstitial injury (0.3 ± 0.1 vs. 0.7 ± 0.1 injury score, respectively), proteinuria (66.3 ± 10.0 vs. 117.5 ± 10.1 mg/day, respectively), and serum creatinine levels (0.5 ± 0.04 vs. 0.9 ± 0.07 mg/dl, respectively). Given that HIRD severity is expected to be a function of renal microvascular BP transmission, BP-renal blood flow (RBF) relationships were examined in additional conscious rats administered ANG II (n = 7) or l-NAME (n = 8). Greater renal vasoconstriction was observed during ANG II versus l-NAME administration (41% vs. 23% decrease in RBF from baseline). Moreover, administration of ANG II, but not l-NAME, led to a unique BP-RBF pattern in which the most substantial decreases in RBF were observed during spontaneous increases in BP. We conclude that the hemodynamic effects of ANG II may mediate the strikingly low susceptibility to HIRD in the ANG II-infused model of hypertension in rats. PMID:25477472

Polichnowski, Aaron J; Griffin, Karen A; Picken, Maria M; Licea-Vargas, Hector; Long, Jianrui; Williamson, Geoffrey A; Bidani, Anil K

2015-02-01

122

Partners In Health and Brigham & Women's Hospitalist Program Background: Partners In Health (PIH) is a health and social justice organization with a  

E-print Network

Partners In Health and Brigham & Women's Hospitalist Program Background: Partners In Health (PIH) is a health and social justice organization with a mission to build high quality, comprehensive public health systems

Derisi, Joseph

123

Agmatine Induced NO Dependent Rat Mesenteric Artery Relaxation and its Impairment in Salt-Sensitive Hypertension  

PubMed Central

L-arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. L-arginine initiated relaxations (EC50, 5.8 ± 0.7 mM; n = 9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3 ± 1.3 mM; n = 5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7 ± 12.1 ?M; n = 22), which was compromised by L-NAME (L-NG-Nitroarginine methyl ester, an eNOS inhibitor), RX821002 (?-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9 ± 23.4 ?M; n = 5). The ?-2A AR, ?-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of ?-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. PMID:23994446

Gadkari, Tushar V.; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M.; Joshi, Mahesh S.

2013-01-01

124

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

125

Serelaxin reduces oxidative stress and asymmetric dimethylarginine in angiotensin II-induced hypertension.  

PubMed

Recent findings suggest the therapeutic action of relaxin during hypertension is dependent on nitric oxide synthase (NOS) activation; however, the mechanisms underlying the beneficial effects of relaxin on the NOS system have not been fully elucidated. We hypothesized that the protective effects of relaxin include reducing both oxidative stress and the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). We examined the effect of Serelaxin [human recombinant relaxin-2 (RLX)] in male Sprague-Dawley rats given high-dose angiotensin (ANG) II (400 ng·kg(-1)·min(-1) sc) for 6 wk or shams. RLX was administered (4 ?g/h sc) to half of the rats in each group after 2 wk of ANG II for the remaining 4 wk. ANG II induced hypertension and proteinuria, reduced NO oxidation products (NOx), and increased oxidative stress (NADPH oxidase activity, thiobarbituric acid-reactive substances, and 8-isoprostane excretion) and plasma ADMA. While RLX had no effect on sham rats, RLX attenuated the ANG II-dependent hypertension (165 ± 5 vs. 135 ± 13 mmHg, P < 0.05) and proteinuria at 6 wk (62 ± 6 vs. 41 ± 4 mg·day(-1)·100 g(-1), P < 0.05) and normalized oxidative stress and circulating ADMA, in association with restored NOx excretion and kidney cortex NOx. We found that RLX had no impact on the ADMA-regulatory enzymes protein arginine methyltransferase and dimethylarginine-dimethylaminohydrolase (DDAH). Furthermore, RLX treatment did not increase DDAH activity in kidney cortex or liver. These data suggest that benefits of RLX treatment include reduced ADMA levels and increased NO bioavailability, possibly due to its antioxidant effects. PMID:25298524

Sasser, Jennifer M; Cunningham, Mark W; Baylis, Chris

2014-12-15

126

Physical training prevents oxidative stress in L-NAME-induced hypertension rats.  

PubMed

The present study investigated the effects of a 6-week swimming training on blood pressure, nitric oxide (NO) levels and oxidative stress parameters such as protein and lipid oxidation, antioxidant enzyme activity and endogenous non-enzymatic antioxidant content in kidney and circulating fluids, as well as on serum biochemical parameters (cholesterol, triglycerides, urea and creatinine) from N?-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension treated rats. Animals were divided into four groups (n = 10): Control, Exercise, L-NAME and Exercise L-NAME. Results showed that exercise prevented a decrease in NO levels in hypertensive rats (P < 0·05). An increase in protein and lipid oxidation observed in the L-NAME-treated group was reverted by physical training in serum from the Exercise L-NAME group (P < 0·05). A decrease in the catalase (CAT) and superoxide dismutase (SOD) activities in the L-NAME group was observed when compared with normotensive groups (P < 0·05). In kidney, exercise significantly augmented the CAT and SOD activities in the Exercise L-NAME group when compared with the L-NAME group (P < 0·05). There was a decrease in the non-protein thiols (NPSH) levels in the L-NAME-treated group when compared with the normotensive groups (P < 0·05). In the Exercise L-NAME group, there was an increase in NPSH levels when compared with the L-NAME group (P < 0·05). The elevation in serum cholesterol, triglycerides, urea and creatinine levels observed in the L-NAME group were reverted to levels close to normal by exercise in the Exercise L-NAME group (P < 0·05). Exercise training had hypotensive effect, reducing blood pressure in the Exercise L-NAME group (P < 0·05). These findings suggest that physical training could have a protector effect against oxidative damage and renal injury caused by hypertension. PMID:22961602

Cardoso, Andréia Machado; Martins, Caroline Curry; Fiorin, Fernando da Silva; Schmatz, Roberta; Abdalla, Fátima Husein; Gutierres, Jessié; Zanini, Daniela; Fiorenza, Amanda Maino; Stefanello, Naiara; Serres, Jonas Daci da Silva; Carvalho, Fabiano; Castro, Verônica Paiva; Mazzanti, Cinthia Melazzo; Royes, Luiz Fernando Freire; Belló-Klein, Adriane; Goularte, Jeferson Ferraz; Morsch, Vera Maria; Bagatini, Margarete Dulce; Schetinger, Maria Rosa Chitolina

2013-03-01

127

Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.  

PubMed

Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension. PMID:21755262

Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarães, D D

2011-09-01

128

Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats.  

PubMed

Hypertension (HT) is a prevailing risk factor for cognitive impairment, the most common cause of vascular dementia; yet, no possible mechanism underlying the cognitive impairment induced by hypertension has been identified so far. Inhibition of PDE-4 has been shown to increase phosphorylation of cAMP-response element binding protein in the hippocampus and enhance the memory performance. Here, we examined the effects of PDE-4 inhibitors, rolipram and roflumilast, on the impairment of learning and memory observed in hypertensive rats. We used 2k-1c hypertensive model to induce learning and memory defects. In addition, mRNA expression of PDE-4 sub-types A-D was also assessed in the hippocampus tissue. Systolic blood pressure (SBP) was measured by tail-cuff method was significantly increased in 2k-1c rats when compared to sham operated rats; this effect was reversed by clonidine, whereas, PDE-4 inhibitors did not. PDE-4 inhibitors significantly reversed time induced memory deficit in novel object recognition task (NORT). Further, the retention latency on the second day in the elevated plus maze model was significantly shortened after repeated administration of rolipram and roflumilast. Plasma and brain concentrations of rolipram, roflumilast and roflumilast N-oxide were also measured after the NORT and showed linear increase in plasma and brain concentrations. The PDE4B and PDE4D gene expression was significantly enhanced in hypertensive rats compared with sham operated however PDE4A and PDE4C remained unaltered. Repeated treatment with PDE-4 inhibitors caused down regulation of PDE4B and PDE4D in hypertensive rats. These results suggest that inhibition of PDE-4 ameliorates HT-induced impairment of learning and memory functions. PMID:25446433

Jabaris, Sobhana George Sugin Lal; Sumathy, Haridass; Kumar, Ramadass Satiesh; Narayanan, Shridhar; Thanikachalam, Sadagopan; Babu, Chidambaram Saravana

2015-01-01

129

Intracerebroventricular Infusion of the (Pro)renin Receptor Antagonist PRO20 Attenuates Deoxycorticosterone Acetate-Salt-Induced Hypertension.  

PubMed

We previously reported that binding of prorenin to the (pro)renin receptor (PRR) plays a major role in brain angiotensin II formation and the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Here, we designed and developed an antagonistic peptide, PRO20, to block prorenin binding to the PRR. Fluorescently labeled PRO20 bound to both mouse and human brain tissues with dissociation constants of 4.4 and 1.8 nmol/L, respectively. This binding was blocked by coincubation with prorenin and was diminished in brains of neuron-specific PRR-knockout mice, indicating specificity of PRO20 for PRR. In cultured human neuroblastoma cells, PRO20 blocked prorenin-induced calcium influx in a concentration- and AT1 receptor-dependent manner. Intracerebroventricular infusion of PRO20 dose-dependently inhibited prorenin-induced hypertension in C57Bl6/J mice. Furthermore, acute intracerebroventricular infusion of PRO20 reduced blood pressure in both DOCA-salt and genetically hypertensive mice. Chronic intracerebroventricular infusion of PRO20 attenuated the development of hypertension and the increase in brain hypothalamic angiotensin II levels induced by DOCA-salt. In addition, chronic intracerebroventricular infusion of PRO20 improved autonomic function and spontaneous baroreflex sensitivity in mice treated with DOCA-salt. In summary, PRO20 binds to both mouse and human PRRs and decreases angiotensin II formation and hypertension induced by either prorenin or DOCA-salt. Our findings highlight the value of the novel PRR antagonist, PRO20, as a lead compound for a novel class of antihypertensive agents and as a research tool to establish the validity of brain PRR antagonism as a strategy for treating hypertension. PMID:25421983

Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng; Worker, Caleb J; Xiong, Zhenggang; Speth, Robert C; Feng, Yumei

2015-02-01

130

Effect of thoracic epidural blockade on hypoxia-induced pulmonary arterial hypertension in rats  

PubMed Central

Objective(s): The present study was aimed to investigate the influence of thoracic epidural blockade on hypoxia-induced pulmonary hypertension in rats. Materials and Methods: Forty eight Wistar rats were randomly divided into 4 equal groups, named normoxia hypoxia hypoxia/ ropivacaine and hypoxia/saline. Animals were placed in a hypoxia chamber and instrumented with epidural catheters at the thoracic level. Rats were injected with saline or ropivacaine. Haemodynamic measurements included pulmonary artery pressure and right ventricular hypertrophy. Degree of pulmonary vascular remodeling was determined by Hematoxylin and Eosin (HE) staining. Serum cyclic GMP (cGMP) and TNF-? were measured using radioimmuno assay. Real-time PCR and western boltting were employed to examine the expression of cAMP responding-element binding protein (CREB). Results: We found that the thoracic epidural blockade significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats. Ropivacaine-treated rats exhibited significantly lower mean pulmonary artery pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery compared with those of control rats. Hypoxia-induced increase in levels of serum cGMP and TNF-? was reversed by thoracic epidural blockade. Moreover, hypoxia increased expression of CREB at mRNA and protein levels which could be suppressed by thoracic epidural blockade. Conclusion: Thoracic epidural blockade reduced mPAP and serum level of TNF-? and increased cGMP. The treatment reversed upregulated expression of CREB at mRNA and protein production.

YU, Shi-huan; CHEN, Jing-ying; ZHANG, Yi-mei; JIAO, Gui-wei; LIU, Feng-qi; KONG, Ling-fei

2014-01-01

131

Hydrogen sulfide is involved in dexamethasone-induced hypertension in rat.  

PubMed

Glucocorticoid (GC)-induced hypertension is a common clinical problem still poorly understood. The presence of GC receptor (GR) in vascular smooth muscle and endothelial cells suggests a direct role for GC in vasculature. In response to hemodynamic shear stress, endothelium tonically releases nitric oxide (NO), endothelial-derived hyperpolarizing factor (EDHF) and prostacyclin contributing to vascular homeostasis. Recently, hydrogen sulfide (H2S) has been proposed as a candidate for EDHF. H2S is endogenously mainly formed from L-cysteine by the action of cystathionine-?-synthase (CBS) and cystathionine-?-lyase (CSE). It plays many physiological roles and contributes to cardiovascular function. Here we have evaluated the role played by H2S in mesenteric arterial bed and in carotid artery harvested from rats treated with vehicle or dexamethasone (DEX; 1.5?mg/kg/day) for 8 days. During treatments systolic blood pressure was significantly increased in conscious rats. EDHF contribution was evaluated in ex-vivo by performing a concentration-response curve induced by acetylcholine (Ach) in presence of a combination of indomethacin and L-NG-Nitroarginine methyl ester in both vascular districts. EDHF-mediated relaxation was significantly reduced in DEX-treated group in both mesenteric bed and carotid artery. EDHF-mediated relaxation was abolished by pre-treatment with both apamin and charybdotoxin, inhibitors of small and big calcium-dependent potassium channels respectively, or with propargylglycine, inhibitor of CSE. Western blot analysis revealed a marked reduction in CBS and CSE expression as well as H2S production in homogenates of mesenteric arterial bed and carotid artery from DEX-treated rats. In parallel, H2S plasma levels were significantly reduced in DEX group compared with vehicle. In conclusion, an impairment in EDHF/H2S signaling occurs in earlier state of GC-induced hypertension in rats suggesting that counteracting this dysfunction may be beneficial to manage DEX-associated increase in blood pressure. PMID:25461303

d'Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Donnarumma, Erminia; Tramontano, Teresa; Brancaleone, Vincenzo; Cirino, Giuseppe; Bucci, Mariarosaria; Sorrentino, Raffaella

2014-11-25

132

Central and Peripheral Mechanisms of T lymphocyte Activation and Vascular Inflammation Produced by Angiotensin II-Induced Hypertension  

PubMed Central

Rationale We have previously found that T lymphocytes are essential for development of angiotensin II-induced hypertension however the mechanisms responsible for T cell activation in hypertension remain undefined. Objective To study the roles of the central nervous system and pressure elevation in T cell activation and vascular inflammation caused by angiotensin II. Methods and Results To prevent the central actions of angiotensin II we created anteroventral third cerebral ventricle (AV3V) lesions in mice. The elevation in blood pressure in response to angiotensin II was virtually eliminated by AV3V lesions, as was activation of circulating T cells and the vascular infiltration of leukocytes. In contrast, AV3V lesioning did not prevent the hypertension and T cell activation caused by the peripheral acting agonist norepinephrine. To determine if T cell activation and vascular inflammation are due to central influences or are mediated by blood pressure elevation, we administered hydralazine (250 mg/L) in the drinking water. Hydralazine prevented the hypertension, and abrogated the increase in circulating activated T cells and vascular infiltration of leukocytes caused by angiotensin II. Conclusions We conclude that the central and pressor effects of angiotensin II are critical for T cell activation and development of vascular inflammation. These findings also support a feed forward mechanism in which modest degrees of blood pressure elevation lead to T cell activation, which in turn promotes inflammation and further raises blood pressure, leading to severe hypertension. Brief summary We have previously shown that T cells are important for the development of hypertension and others have shown that CNS lesions such as AV3V disruption prevent hypertension. We examined the relationship between central actions of angiotensin II, T cell activation and hypertension by determining how AV3V lesions affect T cell activation and hypertensive responses to angiotensin II and norepinephrine. Our data are compatible with a scenario in which modest degrees of pressure elevation, mediated either directly by norepinephrine or via central actions of angiotensin II, promote an inflammatory response that leads to severe hypertension. These studies provide new insight into how the central nervous system contributes to systemic inflammation in hypertension. PMID:20558826

Marvar, Paul J.; Thabet, Salim R.; Guzik, Tomasz J.; Lob, Heinrich E.; McCann, Louise A.; Weyand, Connie; Gordon, Frank J.; Harrison, David G.

2010-01-01

133

Lead Poisoning-Induced Hypertensive Crisis Managed by Prazosin: A Case Report  

PubMed Central

Introduction Chronic lead exposure is known to be a risk factor for hypertension (HTN). No specific medication is recommended for the treatment of lead-induced hypertension (LIHTN). Case Presentation Our patient was a male admitted with the chief complaint of chronic abdominal pain. His whole blood lead level was reported to be 1961 µg/L. He also mentioned a previous history of HTN managed by propranolol (10 mg, TDS). He discharged himself by giving written consent and 19 days later, he was re-admitted due to high blood pressure of 220/140 mmHg. His Blood pressure (BP) was decreased to 180/110 mmHg with sublingual captopril; but, in maintenance therapy, higher doses of captopril could not further decrease BP. Amlodipine was tried which was discontinued due to the patient intolerance. Prazosin was then administered in gradual increasing doses up to 1 mg twice a day and captopril was tapered. Conclusions We would like to suggest that LIHTN may better be managed by alpha blockers compared with converting enzyme inhibitors PMID:24349754

Dadpour, Bita; Mehrpour, Omid; Etemad, Leila; Moshiri, Mohammad

2013-01-01

134

Apoptosis and Inflammation Associated Gene Expressions in Monocrotaline-Induced Pulmonary Hypertensive Rats after Bosentan Treatment  

PubMed Central

Background and Objectives Vascular wall remodeling in pulmonary hypertension can be caused by an aberration in the normal balance between proliferation and apoptosis of endothelial cell in the pulmonary artery. The objective of this study was to evaluate the effect of bosentan on apoptosis in monocrotaline (MCT)-induced pulmonary hypertension. Materials and Methods Sprague-Dawley rats were divided into three groups: control (C) group, M group (MCT 60 mg/kg) and B group (MCT 60 mg/kg plus bosentan 20 mg/day orally). Gene expressions of Bcl (B cell leukemia/lymphoma)-2, caspase-3, complement component (C)-6, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-?) were analyzed by real time polymerase chain reaction and western blot analysis. Results The messenger ribonucleic acid (mRNA) expressions of caspase-3 and VEGF were significantly increased in the M group compared with the C group, and significantly decreased in the B group compared with the M group in week 4. mRNA expression of IL-6 was significantly decreased in weeks 1, 2, and 4 in the B group compared with the M group. mRNA expression of TNF-? was significantly decreased on day 5 and in weeks 1 and 2 in the B group compared with the M group. Conclusion Bosentan may have potential for preventing apoptosis and inflammation. PMID:24653739

Hong, Young Mi; Kwon, Jung Hyun; Choi, Shinkyu

2014-01-01

135

Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms.  

PubMed

We have demonstrated recently [Callera, Touyz, Teixeira, Muscara, Carvalho, Fortes, Schiffrin and Tostes (2003) Hypertension 42, 811-817] that increased vascular oxidative stress in DOCA (deoxycorticosterone acetate)-salt rats is associated with activation of the ET (endothelin) system via ETA receptors. The exact source of ET-1-mediated oxidative stress remains unclear. The aim of the present study was to investigate whether ET-1 increases generation of ROS (reactive oxygen species) in DOCA-salt hypertension through NADPH-oxidase-dependent mechanisms. Xanthine oxidase, eNOS (endothelial nitric oxide synthase) and COX-2 (cyclo-oxygenase-2) were also examined as potential ET-1 sources of ROS as well as mitochondrial respiration. DOCA-salt and control UniNX (uninephrectomized) rats were treated with the ETA antagonist BMS182874 (40 mg.day(-1).kg(-1) of body weight) or vehicle. Plasma TBARS (thiobarbituric acid-reacting substances) were increased in DOCA-salt compared with UniNX rats. Activity of NADPH and xanthine oxidases in aorta, mesenteric arteries and heart was increased in DOCA-salt rats. BMS182874 decreased plasma TBARS levels without influencing NADPH and xanthine oxidase activities in DOCA-salt rats. Increased p22(phox) protein expression and increased p47(phox) membrane translocation in arteries from DOCA-salt by rats were not affected by BMS182874 treatment. Increased eNOS and COX-2 expression, also observed in aortas from DOCA-salt rats, was unaltered by BMS182874. Increased mitochondrial generation of ROS in DOCA-salt rats was normalized by BMS182874. ETA antagonism also increased the expression of mitochondrial MnSOD (manganese superoxide dismutase) in DOCA-salt rats. In conclusion, activation of NADPH oxidase does not seem to be the major source of oxidative stress induced by ET-1/ETA in DOCA-salt hypertension, which also appears to be independent of increased activation of xanthine oxidase or eNOS/COX-2 overexpression. Mitochondria may play a role in ET-1-driven oxidative stress, as evidenced by increased mitochondrial-derived ROS in this model of hypertension. PMID:16271043

Callera, Glaucia E; Tostes, Rita C; Yogi, Alvaro; Montezano, Augusto C I; Touyz, Rhian M

2006-02-01

136

Protein kinase C activation-induced increases of neural activity are enhanced in the hypothalamus of spontaneously hypertensive rats  

Microsoft Academic Search

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these angiotensin II-sensitive neurons in the AHA are enhanced in spontaneously hypertensive rats (SHR). In addition, neural activations induced by both angiotensin II and glutamate were enhanced in the AHA of SHR. In this study,

Takao Kubo; Yukihiko Hagiwara

2005-01-01

137

Prenatal dexamethasone 'programmes' hypotension, but stress-induced hypertension in adult offspring  

Microsoft Academic Search

Low birth weight in humans is predictive of hypertension in adult life. Although the mechanisms underlying this link remain unknown, fetal overexposure to glucocorticoids has been implicated. We previously showed that prenatal dexamethasone (DEX) exposure in the rat lowers birth weight and programmes adult hypertension. The current study aimed to further investigate the nature of this hypertension and to elucidate

David O'Regan; Christopher J Kenyon; Jonathan R Seckl; Megan C Holmes

2008-01-01

138

Orexin A regulates cardiovascular responses in stress-induced hypertensive rats.  

PubMed

Several pieces of evidence indicate that the rostral ventrolateral medulla (RVLM) is probably one of the key neural structures mediating the pressor effects of orexins in the brain. Nitric oxide synthase/nitric oxide (NOS/NO) system in the RVLM modulates cardiovascular activities. Our experiments were designed to test the hypothesis that orexin-A (OXA) is involved in the mechanism of stress-induced hypertension (SIH) by adjusting NOS/NO system in the RVLM. The stress-induced hypertensive rats (SIHR) model was established by electric foot-shocks and noises. Here we examined the expression of OXA immunoreactive (OXA-IR) cells in the lateral hypothalamus (LH) and the protein level of orexin 1 receptor (OX1R) in the RVLM of SIHR, and we found that the expressions of OXA-IR and OX1R were higher than those of the control group. The double-staining immunohistochemical evidence showed that OX1R immunoreactive (OX1R-IR) cells and neuronal nitric oxide synthase (nNOS) or inducible nitric oxide synthase (iNOS) immunoreactive (IR) cells were co-localizated in the RVLM. Microinjection of OXA (10, 50, 100 pmol/100 nl) into the unilateral (right) RVLM of control rats or SIHR produced pressor and tachycardiac effects in a dose-dependent manner. SB-408124 (100 pmol/100 nl, an antagonist of OX1R) or TCS OX2 29 (100 pmol/100 nl, an antagonist of OX2R) partly abolished the cardiovascular effects of exogenously-administrated OXA into the RVLM of control rats and SIHR, and lowered the increased systolic blood pressure (SBP) and heart rate (HR) of SIHR, with no difference in statistical significance between the two antagonists' effects. Microinjection into the RVLM of both control and SIHR groups of 7-Ni (0.05 pmol/100 nl, nNOS inhibitor) or Methylene Blue [100 pmol/100 nl, an inhibitor of soluble guanylate cyclase (sGC)] suppressed the OXA-induced increase of SBP and HR, whereas microinjection of AG (1, 10, 100 pmol/100 nl) had no obvious effects on the OXA-induced increase of SBP and HR. Our results indicate that OXA in the RVLM may participate in the central regulation of cardiovascular activities in SIHR, and OX1R and OX2R both have important roles in it. The cardiovascular effects of OXA in the RVLM may be induced by nNOS-derived NO, which activated sGC-associated signaling pathway. PMID:23147417

Xiao, Fen; Jiang, Meiyan; Du, Dongshu; Xia, Chunmei; Wang, Jin; Cao, Yinxiang; Shen, Linlin; Zhu, Danian

2013-04-01

139

Rats with Hypertension Induced by in utero Exposure to Maternal Low-Protein Diets Fail to Increase Blood Pressure in Response to a High Salt Intake  

Microsoft Academic Search

Hypertension in the rat has been demonstrated to be determined in utero by exposure to maternal low-protein diets. Assessment was made of the response of rats with maternal diet-induced hypertension to a chronic high intake of sodium chloride. Normotensive and hypertensive animals were provided with either drinking water (control) or 1.5% sodium chloride over a 7-day period. Normotensive rats significantly

Simon C. Langley-Evans; Alan A. Jackson

1996-01-01

140

Pulmonary Hypertension  

PubMed Central

The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

Newman, John H.

2005-01-01

141

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

142

Angiotensin-converting enzyme-derived angiotensin II formation during angiotensin II-induced hypertension.  

PubMed

The extent to which endogenous angiotensin (Ang) II formation is responsible for increasing kidney Ang II content and blood pressure during Ang II-induced hypertension is unknown. To address this, mice were treated with an Ang-converting enzyme (ACE) inhibitor (ACEi) to block endogenous Ang II formation during chronic Ang II infusions. C57BL/6J male mice (8 to 12 weeks) were subjected to Ang II infusions (400 ng/kg per minute) with or without an ACEi (lisinopril, 100 mg/L in the drinking water) for 12 days. Blood pressure was monitored by tail-cuff method and telemetry. Ang II content was determined by radioimmunoanalysis. Ang II infusions increased 24-hour mean arterial pressure significantly (141.0+/-3.7 mm Hg) versus controls (110.0+/-1.0 mm Hg). ACEi prevented the increase in concentration in Ang II-infused mice (Ang II+ACEi; 114.0+/-7.4 mm Hg; P value not significant). Plasma Ang II content was significantly increased by Ang II (367+/-60 fmol/mL) versus controls (128+/-22 fmol/mL; P<0.05); plasma Ang II was not altered by ACEi alone (90+/-31) or in combination with Ang II infusions (76+/-27). Intrarenal Ang II content was significantly increased by Ang II (998+/-143 fmol/g) versus controls (524+/-60 fmol/g; P<0.05), and this was prevented by ACEi (Ang II+ACEi; 484+/-102 fmol/g; P value not significant). Thus, ACEi ameliorates the increases in blood pressure and intrarenal Ang II content caused by Ang II infusions, indicating that endogenous ACE-mediated Ang II formation plays a significant role in the increases of blood pressure and intrarenal Ang II during Ang II-induced hypertension. PMID:19075090

Gonzalez-Villalobos, Romer A; Satou, Ryousuke; Seth, Dale M; Semprun-Prieto, Laura C; Katsurada, Akemi; Kobori, Hiroyuki; Navar, L Gabriel

2009-02-01

143

CYP4A2-induced hypertension is 20-hydroxyeicosatetraenoic acid- and angiotensin II-dependent.  

PubMed

We have shown previously that increased vascular endothelial expression of CYP4A2 leads to 20-hydroxyeicosatetraenoic (20-HETE)-dependent hypertension. The renin-angiotensin system is a key regulator of blood pressure. In this study, we examined possible interactions between 20-HETE and the renin-angiotensin system. In normotensive (110±3 mm Hg) Sprague-Dawley rats transduced with a lentivirus expressing the CYP4A2 cDNA under the control of an endothelial-specific promoter (VECAD-4A2), systolic blood pressure increased rapidly, reaching 139±1, 145±3, and 150±2 mm Hg at 3, 5, and 10 days after transduction; blood pressure remained elevated, thereafter, with maximum levels of 163±3 mm Hg. Treatment with lisinopril, losartan, or the 20-HETE antagonist 20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid decreased blood pressure to control values, but blood pressure returned to its high levels after cessation of treatment. Endothelial-specific overexpression of CYP4A2 resulted in increased expression of vascular angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor and increased levels of plasma and tissue angiotensin II; all were attenuated by treatment with HET0016, an inhibitor of 20-HETE synthesis, or with 20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid. In cultured endothelial cells, 20-HETE specifically and potently induced ACE expression without altering the expression of ACE2, angiotensinogen, or angiotensin II receptors. This is the first study to demonstrate that 20-HETE, a key constrictor eicosanoid in the microcirculation, induces ACE and angiotensin II type 1 receptor expression and increases angiotensin II levels, suggesting that the mechanisms by which 20-HETE promotes hypertension include activation of the renin-angiotensin system that is likely initiated at the level of ACE induction. PMID:20837888

Sodhi, Komal; Wu, Cheng-Chia; Cheng, Jennifer; Gotlinger, Katherine; Inoue, Kazuyoshi; Goli, Mohan; Falck, John R; Abraham, Nader G; Schwartzman, Michal L

2010-11-01

144

Heme-arginate suppresses phospholipase C and oxidative stress in the mesenteric arterioles of mineralcorticoid-induced hypertensive rats  

Microsoft Academic Search

Induction of heme-oxygenase (HO) is an important cellular defense mechanism against oxidative and inflammatory insults. We analyzed the effects of the HO inducer, heme-arginate, on the phospholipase C (PLC)\\/inositol-triphosphate (IP3) pathway in the mesenteric arterioles of uninephrectomized (UnX) deoxycorticosterone acetate (DOCA)-salt hypertensive rats, which is a volume-overload model characterized by elevated endothelin (ET-1) and mineralocorticoid-induced oxidative\\/inflammatory insults. Our study included

Joseph Fomusi Ndisang; Ashok Jadhav

2010-01-01

145

Effect of A-HRS on blood pressure and metabolic alterations in fructose-induced hypertensive rats  

Microsoft Academic Search

Fructose feeding induces a rise in blood pressure in normal rats that is associated with insulin resistance, hyperinsulinemia, hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia. We have examined the effect of chronic administration of A-HRS (100 and 300?mg?kg; p.o.) isolated from Hibiscus rosa sinensis (Malvaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, uric acid and insulin in fructose-induced hypertension

Mahalaxmi Mohan; Bhagyashree Khade; Amol Shinde

2011-01-01

146

Effect of A-HRS on blood pressure and metabolic alterations in fructose-induced hypertensive rats  

Microsoft Academic Search

Fructose feeding induces a rise in blood pressure in normal rats that is associated with insulin resistance, hyperinsulinemia, hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia. We have examined the effect of chronic administration of A-HRS (100 and 300?mg?kg; p.o.) isolated from Hibiscus rosa sinensis (Malvaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, uric acid and insulin in fructose-induced hypertension

Mahalaxmi Mohan; Bhagyashree Khade; Amol Shinde

2012-01-01

147

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

148

Predictive factor and antihypertensive usage of tyrosine kinase inhibitor-induced hypertension in kidney cancer patients  

PubMed Central

Hypertension (HT) is the common adverse event associated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKI). The present study was performed to identify the predictive factors of TKI-induced HT and to determine the classes of antihypertensive agents (AHTA) that demonstrate optimal efficacy against this type of HT. The charts of 50 cases of patients that had received VEGFR-TKI treatment were retrospectively examined. The association between patient background and TKI-induced HT, and the effect of administering AHTA were analyzed. High systolic blood pressure at baseline was identified to be a predictive factor for HT. In addition, there was no difference observed between calcium channel blockers (CCBs) and angiotensin receptor II blockers (ARBs) as first-line AHTA for the control of HT. The findings of the present study may aid with predicting the onset of TKI-induced HT, as well as for its management via the primary use of either CCBs or ARBs. PMID:24959266

IZUMI, KOUJI; ITAI, SHINGO; TAKAHASHI, YOSHIKO; MAOLAKE, AERKEN; NAMIKI, MIKIO

2014-01-01

149

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

150

A putative role for hypothalamic glucocorticoid receptors in hypertension induced by prenatal undernutrition in the rat.  

PubMed

Prenatal undernutrition induces hypertension later in life, possibly by disturbing the hypothalamo-pituitary-adrenal axis through programming decreased expression of hypothalamic glucocorticoid receptors. We examined the systolic blood pressure, heart rate and plasma corticosterone response to intra-paraventricular dexamethasone, mifepristone and corticosterone in eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily (40% of diet consumed by well-nourished controls). At day 40 of postnatal life (i) intra-paraventricular administration of dexamethasone significantly reduced at least for 24h both the systolic pressure (-11.6%), the heart rate (-20.8%) and the plasma corticosterone (-40.0%) in normal animals, while producing lower effects (-5.5, -8.7, and -22.3%, respectively) on undernourished rats; (ii) intra-paraventricular administration of the antiglucocorticoid receptor ligand mifepristone to normal rats produced opposite effects (8.2, 20.3, and 48.0% increase, respectively) to those induced by dexamethasone, being these not significant in undernourished animals; (iii) intra-paraventricular corticosterone did not exert any significant effect. Results suggest that the low sensitivity of paraventricular neurons to glucocorticoid receptor ligands observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor expression, found in the hypothalamus of undernourished animals. PMID:20674672

Pérez, Hernán; Soto-Moyano, Rubén; Ruiz, Samuel; Hernández, Alejandro; Sierralta, Walter; Olivares, Ricardo; Núñez, Héctor; Flores, Osvaldo; Morgan, Carlos; Valladares, Luis; Gatica, Arnaldo; Flores, Francisco J

2010-10-01

151

Endothelin-1 receptor antagonist BQ123 prevents pulmonary artery hypertension induced by low ambient temperature in broilers.  

PubMed

Evidence has indicated that endothelin-1 is related to the pathogenesis of hypertension. To characterize the role of endothelin-1 (ET-1) in the development of pulmonary hypertension syndrome in broilers, the blockade effect of ETA receptor (ET(A)) antagonist, BQ123, on blood pressure in experimental models of pulmonary hypertension was examined. Birds were locally anesthetized and instrumented with venous catheters for pulmonary arterial pressure (PAP) and right ventricular pressure (RVP), followed by packed cell volume (PCV) and Ascites heart index (AHI) measured, after exposed to low ambient temperature for 7 or 14 d. In treated groups, BQ123 (0.4 or 2.0 microg each time, 2 times a day), administered in abdominal cavities for 7 or 14 d during birds kept in low ambient temperature, prevented both PAP and RVP increasing, especially the high dose BQ123 lowered PAP and RVP to normotensive levels as that in control under normal temperature, whereas significant increases (p<0.05) were found in the two parameters of broilers in both untreated and saline treated group under low ambient temperature compared with those of birds in control. Furthermore, there was also a reduction in low ambient temperature-induced right ventricular hypertrophy in the groups administered BQ123. The preventive effect of BQ123 suggests that ET-1 is associated with the development of broilers' pulmonary hypertension, which leads to the development of ascites, and BQ123 can prevent the occurrence of pulmonary hypertension. PMID:16327149

Yang, Ying; Qiao, Jian; Wu, Zhenlong; Chen, Yue; Gao, Mingyu; Ou, Deyuan; Wang, Huiyu

2005-12-01

152

Effect of Chronic Sodium Nitrite Therapy on Monocrotaline-Induced Pulmonary Hypertension  

PubMed Central

Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3 mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent. PMID:22426035

Pankey, Edward A.; Badejo, Adeleke M.; Casey, David B.; Lasker, George F.; Riehl, Russel A.; Murthy, Subramanyam N.; Nossaman, Bobby D.; Kadowitz, Philip J.

2012-01-01

153

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

Microsoft Academic Search

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 20min of either air jet stress (AJS) or air noise alone (CON). AJS induced a significant increase

Karen Porter; Linda F. Hayward

2011-01-01

154

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

155

Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in L-NAME induced hypertensive rats.  

PubMed

The present study was undertaken to assess the antihypertensive and antioxidant effects of veratric acid on N(?)-nitro-L arginine methyl ester (L-NAME) induced hypertensive rats. Hypertension was induced in adult male albino rats of the Wistar strain, weighing 180-220 g, by oral administration of the L-NAME (40 mg/kg body weight/day) in drinking water for 4 weeks. Rats were treated with various doses of veratric acid (20, 40, 80 mg/kg/day) for four weeks. Hypertension was manifested by considerably increased systolic and diastolic blood pressure and the toxic effect of L-NAME was determined using lipid peroxidative markers (thiobarbituric acid reactive substances and lipid hydroperoxides). We also assessed the activities of enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and measured the levels of non-enzymatic antioxidants (vitamin-C, vitamin-E and reduced glutathione) levels in erythrocytes, plasma and tissues and plasma nitric oxide metabolites (nitrite/nitrate). Oral administration of veratric acid at the dosage of 40 mg/kg considerably decreased systolic and diastolic blood pressure, lipid peroxidation products; increased plasma nitric oxide levels and showed no toxicity which was measured using hepatic and renal function markers when compared to other doses of veratric acid (20, 80 mg/kg). In addition, histopathological findings of veratric acid treated hypertensive rat heart confirmed the biochemical findings of this study. These results suggest that veratric acid decreased the blood pressure, significantly restored nitric oxide, enzymatic and non-enzymatic antioxidants and reduced lipid peroxidation products and thus exhibits antihypertensive and antioxidant effects against l-NAME induced hypertension. PMID:21937012

Saravanakumar, Murugesan; Raja, Boobalan

2011-12-01

156

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

157

Endothelin-3-dependent pulmonary vasoconstriction in monocrotaline-induced pulmonary arterial hypertension  

PubMed Central

Blockade of the endothelin (ET) system is beneficial in pulmonary arterial hypertension (PAH). The contribution of ET-3 and its interactions with ET receptors have never been evaluated in the monocrotaline (MCT)-induced model of PAH. Vasoreactivity of pulmonary arteries was investigated; ET-3 localization was determined by confocal imaging and gene expression of prepro-ET-3 quantified using RT-PCR. ET-3 plasma levels tended to increase in PAH. ET-3 localized in the media of pulmonary arteries, where gene expression of prepro-ET-3 was reduced in PAH. ET-3 induced similar pulmonary vasoconstrictions in sham and PAH rats. In sham rats, the ETA antagonist A-147627 (10 nmol/l) significantly reduced the maximal response to ET-3 (Emax 77 ± 1 to 46 ± 2%, mean ± S.E.M., P < 0.001), while the ETB antagonist A-192621 (1 ?mol/l) reduced the sensitivity (EC50 21 ± 7 to 59 ± 16 nmol/l, P < 0.05) without affecting Emax. The combination of both antagonists completely abolished ET-3-induced pulmonary vasoconstriction. In PAH, the ETA antagonist further reduced the maximal response to ET-3 and shifted the EC50 (Emax 23 ± 2%, P < 0.001, EC50 104 ± 24 nmol/l, P < 0.05), while the ETB antagonist only shifted the EC50 (123 ± 36 nmol/l, P < 0.05) without affecting the Emax. In PAH, dual ET receptor inhibition did not further reduce constriction compared to selective ETA inhibition. ET-3 significantly contributes to pulmonary vasoconstriction by activating the ETB at low concentration, and the ETA at high concentration. The increased inhibitory effect of the ETA antagonist in PAH suggests that the contribution of ETB to ET-3-induced vasoconstriction is reduced. Although ET-3 is a potent pulmonary vasoconstrictor in PAH, its potential pathophysiologic contribution remains uncertain. PMID:18771698

Sauvageau, Stéphanie; Thorin, Eric; Villeneuve, Louis; Dupuis, Jocelyn

2013-01-01

158

Valproic acid prevents the deregulation of lipid metabolism and renal renin-angiotensin system in L-NAME induced nitric oxide deficient hypertensive rats.  

PubMed

The present study was aimed to investigate the antihyperlipidemic and renoprotective potential of valproic acid against N(?)-nitro-L arginine methyl ester hydrochloride (L-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), kidney weight, levels of oxidative stress markers in tissues were increased. Dyslipidemia was also observed in hypertensive rats. Moreover, enzymatic and nonenzymatic antioxidant network also deregulated in tissues. Valproic acid (VPA) supplementation daily for four weeks brought back all the above parameters to near normal level and showed no toxicity which was established using serum hepatic marker enzyme activities and renal function markers. Moreover the up regulated expression of renin-angiotensin system (RAS) components were also attenuated by VPA treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that VPA has enough potential to attenuate hypertension, dyslipidemia and renal damage in nitric oxide deficiency induced hypertension. PMID:24705342

Rajeshwari, Thiyagarajan; Raja, Boobalan; Manivannan, Jeganathan; Silambarasan, Thangarasu; Dhanalakshmi, Thanikkodi

2014-05-01

159

Deficiency of the interleukin 17/23 axis accelerates renal injury in mice with deoxycorticosterone acetate+angiotensin ii-induced hypertension.  

PubMed

T cells participate in angiotensin II (Ang II)-induced hypertension. However, the specific subsets of T cells that are important in the end-organ damage are unknown. T-helper 17 cells are a recently identified subset that produces interleukin 17 (IL-17) and requires interleukin 23 (IL-23) for expansion. To evaluate the role of the T-helper 17 immune response in hypertensive renal and cardiac end-organ damage, hypertension was induced with deoxycorticosterone acetate (DOCA)+Ang II in wild-type (n=39) and IL-17-deficient (n=31) mice. The injury was evaluated at day 4 and day 14. To inactivate the IL-17/IL-23 axis at a different point, DOCA+Ang II hypertension was also induced in IL-23p19-deficient mice. Renal infiltration by T-helper 17 cells was increased in hypertensive wild-type mice. Systolic blood pressure did not differ between hypertensive IL-17-deficient and wild-type mice. Three days after induction of hypertension, a significantly higher albuminuria was found in IL-17-deficient than in wild-type mice (196±64 versus 58±16 mg/mg albumin/creatinine). Histology revealed significantly more glomerular injury (1.04±0.06 versus 0.67±0.05) and renal infiltration of ?? T cells in IL-17-deficient than in wild-type mice after 14 days. Similarly, significantly higher albuminuria, glomerular injury, and ?? T cell infiltration were found in IL-23p19-deficient mice with DOCA+Ang II-induced hypertension. DOCA+Ang II also induced cardiac damage as assessed by heart weight, cardiac fibrosis, as well as expression of fetal genes and matrix components, but no significant differences were found among IL-17(-/-), IL-23p19(-/-), and wild-type mice. IL-17/IL-23 deficiency accelerates DOCA+Ang II-induced albuminuria and hypertensive renal but not cardiac end-organ damage. PMID:24366079

Krebs, Christian F; Lange, Sascha; Niemann, Gianina; Rosendahl, Alva; Lehners, Alexander; Meyer-Schwesinger, Catherine; Stahl, Rolf A K; Benndorf, Ralf A; Velden, Joachim; Paust, Hans-Joachim; Panzer, Ulf; Ehmke, Heimo; Wenzel, Ulrich O

2014-03-01

160

Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension.  

PubMed

Severe pulmonary hypertension is a debilitating disease with an alarmingly low 5-yr life expectancy. Hypoxia, one of the causes of pulmonary hypertension, elicits constriction and remodeling of the pulmonary arteries. We now know that pulmonary arterial remodeling is a consequence of hyperplasia and hypertrophy of pulmonary artery smooth muscle (PASM), endothelial, myofibroblast, and stem cells. However, our knowledge about the mechanisms that cause these cells to proliferate and hypertrophy in response to hypoxic stimuli is still incomplete, and, hence, the treatment for severe pulmonary arterial hypertension is inadequate. Here we demonstrate that the activity and expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, are increased in hypoxic PASM cells and in lungs of chronic hypoxic rats. G6PD overexpression and -activation is stimulated by H2O2. Increased G6PD activity contributes to PASM cell proliferation by increasing Sp1 and hypoxia-inducible factor 1? (HIF-1?), which directs the cells to synthesize less contractile (myocardin and SM22?) and more proliferative (cyclin A and phospho-histone H3) proteins. G6PD inhibition with dehydroepiandrosterone increased myocardin expression in remodeled pulmonary arteries of moderate and severe pulmonary hypertensive rats. These observations suggest that altered glucose metabolism and G6PD overactivation play a key role in switching the PASM cells from the contractile to synthetic phenotype by increasing Sp1 and HIF-1?, which suppresses myocardin, a key cofactor that maintains smooth muscle cell in contractile state, and increasing hypoxia-induced PASM cell growth, and hence contribute to pulmonary arterial remodeling and pathogenesis of pulmonary hypertension. PMID:25480333

Chettimada, Sukrutha; Gupte, Rakhee; Rawat, Dhwajbahadur; Gebb, Sarah A; McMurtry, Ivan F; Gupte, Sachin A

2015-02-01

161

Glycyrrhizin could reduce ocular hypertension induced by triamcinolone acetonide in rabbits  

PubMed Central

Purpose To evaluate the hypotensive effects of glycyrrhizin (GL) on a rabbit model of ocular hypertension (OH) induced by triamcinolone acetonide (TA). Methods Forty New Zealand White Rabbits were divided as follows: control (intravitreal injection of sterile saline solution); GL (intravitreal injection of sterile saline solution, then fed with 25mg GL/day); TA (intravitreal TA injection); TA+GL (intravitreal TA injection, then fed with GL) and GL+TA (pre-treated with GL for 3 days, then got TA injection and the following GL treatment). Intraocular pressure (IOP), flash electroretinogram (flash ERG) and flash visual evoked potential (flash VEP) were measured during the follow-up (28 days). The aqueous humor was analyzed, using 1H-nuclear magnetic resonance spectroscopy and principal components analysis (PCA). Results IOP elevation was observed in the TA group during the follow-up, compared to the controls (p<0.01). The IOP was decreased in the TA+GL group and the GL+TA group, compared to the TA group (p<0.05). Both in flash ERG and VEP, the amplitudes were decreased, and the implicit time was prolonged in the TA group, compared to the controls (p<0.05); and the parameters were improved after intervention of GL, compared to the TA group (p<0.05). PCA results indicated that TA could affect ocular metabolism (especially the sugar metabolism), and GL could inhibit it. Conclusions The administration of GL could suppress OH induced by TA in rabbits, and improve their electrophysiological parameters. Metabolomics is a useful tool in ophthalmology research. Our results indicate that TA-induced ocular metabolism changes could be compensated by GL. PMID:21850181

Song, Zhengyu; Gong, Yuanyuan; Liu, Haiyun; Ren, Qiushi

2011-01-01

162

Ultrastructural Changes Associated With Dexamethasone-Induced Ocular Hypertension in Mice  

PubMed Central

Purpose. To determine whether dexamethasone (DEX)-induced ocular hypertension (OHT) in mice mimics the hallmarks of steroid-induced glaucoma (SIG) in humans, including reduced conventional outflow facility (C), increased extracellular matrix (ECM), and myofibroblasts within the outflow pathway. Methods. Osmotic mini-pumps were implanted subcutaneously into C57BL/6J mice for systemic delivery of DEX (3–4 mg/kg/d, n = 31 mice) or vehicle (n = 28). IOP was measured weekly by rebound tonometry. After 3 to 4 weeks, mice were euthanized and eyes enucleated for ex vivo perfusion to measure C, for electron microscopy to examine the trabecular meshwork (TM) and Schlemm's canal (SC), or for immunohistochemistry to examine type IV collagen and ?-smooth muscle actin. The length of basement membrane material (BMM) was measured along the anterior-posterior extent of SC by electron microscopy. Ultrastructural changes in BMM of DEX-treated mice were compared against archived human SIG specimens. Results. Dexamethasone increased IOP by 2.6 ± 1.6 mm Hg (mean ± SD) over 3 to 4 weeks and decreased C by 52% ± 17% versus controls. Intraocular pressure elevation correlated with decreased C. Dexamethasone treatment led to increased fibrillar material in the TM, plaque-like sheath material surrounding elastic fibers, and myofibroblasts along SC outer wall. The length of BMM underlying SC was significantly increased in mice with DEX and in humans with SIG, and in mice decreased C correlated with increased BMM. Conclusions. Dexamethasone-induced OHT in mice mimics hallmarks of human SIG within 4 weeks of DEX treatment. The correlation between reduced C and newly formed ECM motivates further study using DEX-treated mice to investigate the pathogenesis of conventional outflow obstruction in glaucoma. PMID:25028360

Overby, Darryl R.; Bertrand, Jacques; Tektas, Ozan-Yüksel; Boussommier-Calleja, Alexandra; Schicht, Martin; Ethier, C. Ross; Woodward, David F.; Stamer, W. Daniel; Lütjen-Drecoll, Elke

2014-01-01

163

Immunoglobulin G anti-endothelial cell antibodies: inducers of endothelial cell apoptosis in pulmonary arterial hypertension?  

PubMed

Endothelial cell (EC) apoptosis seems to play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). We aimed to test the hypothesis that circulating anti-endothelial cell antibodies (AECA) of PAH patients induce EC apoptosis. Immunoglobulin (Ig)G was purified from sera of PAH patients (n?=?26), patients with systemic lupus erythematosus (SLE) nephritis without PAH (n?=?16), patients with systemic sclerosis (SSc) without PAH (n?=?58) and healthy controls (n?=?14). Human umbilical vein endothelial cells (HUVECs) were incubated with patient or healthy control IgG for 24?h. Thereafter, apoptosis was quantified by annexin A5 binding and hypoploid cell enumeration by flow cytometry. Furthermore, real-time cell electronic sensing (RT-CES™) technology was used to monitor the effects of purified IgG from patient and healthy control IgG on HUVECs. As demonstrated previously, IgG of AECA-positive SLE nephritis patients (n?=?7) induced a higher percentage of apoptosis of HUVECs compared to IgG of AECA-negative SLE nephritis patients and healthy controls. Furthermore, IgG of AECA-positive SLE nephritis patients induced a marked decrease in cell index as assessed by RT-CES™ technology. IgG of AECA-positive PAH patients (n?=?12) and SSc patients (n?=?13) did not alter the percentage of HUVEC apoptosis or cell index compared to IgG of AECA-negative PAH and SSc patients and healthy controls. AECA-positive PAH patients, in contrast to SLE nephritis patients, do not have circulating IgG AECA that enhances apoptosis of HUVECs?in vitro. Further studies should focus on other mechanisms by which AECA may enhance EC apoptosis in PAH, such as antibody-dependent cell-mediated cytotoxicity. PMID:23815467

Arends, S J; Damoiseaux, J G M C; Duijvestijn, A M; Debrus-Palmans, L; Vroomen, M; Boomars, K A; Brunner-La Rocca, H-P; Reutelingsperger, C P M; Cohen Tervaert, J W; van Paassen, P

2013-12-01

164

Mutant Human Myocilin Induces Strain Specific Differences in Ocular Hypertension and Optic Nerve Damage in Mice  

PubMed Central

Elevated intraocular pressure (IOP) is a causative risk factor for the development and progression of glaucoma. Glaucomatous mutations in myocilin (MYOC) damage the trabecular meshwork and elevate IOP in humans and in mice. Animal models of glaucoma are important to discover and better understand molecular pathogenic pathways and to test new glaucoma therapeutics. Although a number of different animal models of glaucoma have been developed and characterized, there are no true models of human primary open angle glaucoma (POAG). The overall goal of this work is to develop the first inducible mouse model of POAG using a human POAG relevant transgene (i.e. mutant MYOC) expression in mouse eyes to elevate IOP and cause pressure induced damage to the optic nerve. Four mouse strains (A/J, BALB/cJ, C57BL/6J, and C3H/HeJ) were used in this study. Ad5.MYOC.Y437H (5 × 107 pfu) was injected intravitreally into one eye, with the uninjected contralateral eye serving as the control eye. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Optic nerve damage was determined by scoring PPD stained optic nerve cross sections. Retinal ganglion cell and superior colliculus damage was assessed by Nissl stain cell counts. Intravitreal administration of viral vector Ad5.MYOC.Y437H caused a prolonged, reproducible, and statistically significant IOP elevation in BALB/cJ, A/J, and C57BL/6J mice. IOPs increased to approximately 25 mm Hg for 8 weeks (p<0.0001). In contrast, the C3H/HeJ mouse strain was resistant to Ad5.MYOC.Y437H induced IOP elevation for the 8-week time period. IOPs were stable (12–15 mm Hg) in the uninjected control eyes. We also determined whether there were any strain differences in pressure-induced optic nerve damage. Even though IOP was similarly elevated in three of the strains tested (BALB/cJ, C57BL/6J, and A/J ) only the A/J strain had considerable and significant optic nerve damage at the end of 8 weeks with optic nerve damage score of 2.64 +/? 0.19 (n=18, p<0.001) in the injected eye. There was no statistical difference in retinal ganglion cell death or superior colliculus damage at the 8-week time point in any of the strains tested. These results demonstrate strain dependent responses to Ad5.MYOC.Y437H-induced ocular hypertension and pressure-induced optic nerve damage. PMID:22575566

McDowell, Colleen M.; Luan, Tomi; Zhang, Zhang; Putliwala, Tasneem; Wordinger, Robert J.; Millar, J. Cameron; John, Simon W.M.; Pang, Iok-Hou; Clark, Abbot F.

2012-01-01

165

Low ethanol intake prevents salt-induced hypertension in WKY rats  

Microsoft Academic Search

Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue

Sudesh Vasdev; Vicki Gill; Sushil Parai; Veeresh Gadag

2006-01-01

166

Content of HSP70 in rats with hereditary stress-induced arterial hypertension  

Microsoft Academic Search

Sensitivity of normotensive Wistar rats and NISAG rats (with hereditary arterial hypertension) to heat stress is compared\\u000a at the organism and cell levels. High temperature sensitivity of NISAG rats correlates with a low content of the main heat\\u000a shock protein HSP70. This relationship can serve as a biochemical marker of predisposition to arterial hypertension.

G. V. Petrova; V. A. Adarichev; A. A. Krivenko; G. S. Dymshits; G. S. Yakobson

1997-01-01

167

A Search for Genetic Loci Responsible for Stress-Induced Arterial Hypertension in the ISIAH Rats  

Microsoft Academic Search

Hypertension is a widespread human disease caused by a complex interaction of a series of the genetic factors with both each other and the environmental conditions. In this study we aimed at determining the candidate genetic loci responsible for hypertension in the ISIAH rats and studying the dynamics of the relevant genetic and physiological mechanisms in rat ontogeny. The candidate

O. E. Redina; J. V. Khvorostova; G. M. Dymshits; A. L. Markel

2003-01-01

168

Function of the Hypothalamo-Pituitary-Adrenocortical System during Ontogenesis in Rats with Inherited Stress-Induced Arterial Hypertension  

Microsoft Academic Search

The functional activity of the hypothalamo-pituitary-adrenocortical system (HPAS) during the development of rats with inherited stress-induced arterial hypertension (HSIAH rats) was compared with that in normotensive Wistar rats. In rats aged 2, 3, 4, 6, 8, 10, 12, and 18 weeks, competitive protein binding assays were used to estimate peripheral blood plasma corticosterone levels at rest and after 1 h

V. V. Bulygina; L. N. Maslova

2002-01-01

169

Activity of 11?-hydroxysteroid dehydrogenase of rat kidney and liver in inherited stress-induced arterial hypertension  

Microsoft Academic Search

11?-hydroxysteroid dehydrogenase (11?-HSD) catalyzing the interconversion of corticosterone and 11-dehydrocorticosterone is\\u000a the key enzyme of glucocorticoid metabolism in rats. The activity of 11?-HSD in kidney of rats with inherited stress-induced\\u000a arterial hypertension (ISIAH) was significantly (p < 0.05) higher than that in WAG rats. The opposite was observed in activity of liver 11?-HSD. No changes in the kidney 11?-HSD\\u000a activity

O. P. Cherkasova

2007-01-01

170

Betulinic acid ameliorates endothelium-dependent relaxation in l-NAME-induced hypertensive rats by reducing oxidative stress  

Microsoft Academic Search

Zizyphi Spinosi semen (ZSS) is one of the most widely used traditional Chinese herbs with protective effects on the cardiovascular system. It is not clear whether betulinic acid (BA), the key active constituent of ZSS, has beneficial cardiovascular effects on N?-nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. The objective of this study was to investigate the effect of BA on

Jia-Yin Fu; Ling-Bo Qian; Lie-Gang Zhu; Hao-Te Liang; Yi-Nuo Tan; Han-Ti Lu; Jian-Feng Lu; Hui-Ping Wang; Qiang Xia

2011-01-01

171

Role of Acetylcholine, Corticoids and Opioids in the Rostral Ventrolateral Medulla in Stress-Induced Hypertensive Rats  

Microsoft Academic Search

Hypertension was induced in Sprague-Dawley and Wistar rats by irregular foot shocks combined with a buzzing noise for 2 h twice a day for 1–2 weeks. The plasma catecholamine, cortico-sterone, angiotensin II, glucose and lipids were found to increase in parallel. The acetylcholine (ACh) and choline acetyltransferase in rostral ventrolateral medulla (rVLM) increased markedly. Microinjection of ACh or cholinergic agonists

P. Li; D.-N. Zhu; K.-M. Kao; Q. Lin; S.-Y. Sun

1995-01-01

172

Factors Involved in the Development of Hypertension Induced by a Low-Protein Diet in Rats with Renal Injury  

Microsoft Academic Search

Background\\/Aims: While a low-protein diet (LPD) has been reported to increase blood pressure, the mechanism for its increase has not yet been clarified. We investigated the factors involved in the development of hypertension induced by LPD in rats with post-cyclosporine (CsA) nephropathy, and determined the appropriate composition for LPD that is to be utilized for renal research. Methods: The rats

Michiyo Endoh; Mari Odamaki; Naoki Ikegaya; Hiromichi Kumagai

2004-01-01

173

Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity.  

PubMed

Previous studies have shown that expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT4 rather than on some systemic effect we developed and tested smooth-muscle-specific GLUT4 transgenic mice (SMG4). When made hypertensive with angiotensin II, both wild-type and SMG4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin F2? was significantly increased in endothelium-intact aortic rings from hypertensive wild-type mice but not in aortae of SMG4 mice. Inhibition of Rho-kinase equally reduced serotonin-stimulated contractility in aortae of hypertensive wild-type and SMG4-mice. In addition, acetylcholine-stimulated relaxation was significantly decreased in aortic rings of hypertensive wild-type mice, but not in rings of SMG4 mice. Inhibition of either prostacylin receptors or cyclooxygenase-2 reduced relaxation in rings of hypertensive SMG4 mice. Inhibition of cyclooxygenase-2 had no effect on relaxation in rings of hypertensive wild-type mice. Cyclooxygenase-2 protein expression was decreased in hypertensive wild-type aortae but not in hypertensive SMG4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT4 exerts a major effect on smooth muscle contractile responses and endothelium-dependent vasorelaxation and that normal expression of GLUT4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses. PMID:25677552

Atkins, Kevin B; Seki, Yoshinori; Saha, Jharna; Eichinger, Felix; Charron, Maureen J; Brosius, Frank C

2015-02-01

174

Blood pressure lowering effect of an olive leaf extract (Olea europaea) in L-NAME induced hypertension in rats.  

PubMed

A specially prepared olive leaf extract (EFLA 943) has been tested for its blood pressure lowering activity in rats rendered hypertensive by daily oral doses of L-NAME (NG-nitro-L-arginine methyl ester, 50 mg/kg) for at least 4 weeks. Oral administration of the extract at different dose levels at the same time as L-NAME for a period of 8 weeks showed a dose dependent prophylactic effect against the rise in blood pressure induced by L-NAME, best effects being induced by a dose of 100 mg/kg of the extract. In rats previously rendered hypertensive by L-NAME for 6 weeks and then treated with that dose of the extract for a further 6 weeks without discontinuation of L-NAME, normalisation of the blood pressure was observed. The findings confirm previous reports on the hypotensive effects of olive leaf. The special extract, EFLA 943, was shown to give consistent results with little individual variability. The antihypertensive effect of the extract may be related to a variety of factors involving reversal of vascular changes involved in the L-NAME induced hypertension. PMID:12489249

Khayyal, Mohamed T; el-Ghazaly, Mona A; Abdallah, Dalal M; Nassar, Noha N; Okpanyi, Samuel N; Kreuter, Matthias-Heinrich

2002-01-01

175

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

176

Cardiac HDAC6 catalytic activity is induced in response to chronic hypertension.  

PubMed

Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown. Genetic studies have suggested that class I HDACs promote pathological cardiac remodeling, while class IIa HDACs are protective. In contrast, nothing is known about the function or regulation of class IIb HDACs in the heart. We developed assays to quantify catalytic activity of distinct HDAC classes in left and right ventricular cardiac tissue from animal models of hypertensive heart disease. Class I and IIa HDAC activity was elevated in some but not all diseased tissues. In contrast, catalytic activity of the class IIb HDAC, HDAC6, was consistently increased in stressed myocardium, but not in a model of physiologic hypertrophy. HDAC6 catalytic activity was also induced by diverse extracellular stimuli in cultured cardiac myocytes and fibroblasts. These findings suggest an unforeseen role for HDAC6 in the heart, and highlight the need for pre-clinical evaluation of HDAC6-selective inhibitors to determine whether this HDAC isoform is pathological or protective in the setting of cardiovascular disease. PMID:21539845

Lemon, Douglas D; Horn, Todd R; Cavasin, Maria A; Jeong, Mark Y; Haubold, Kurt W; Long, Carlin S; Irwin, David C; McCune, Sylvia A; Chung, Eunhee; Leinwand, Leslie A; McKinsey, Timothy A

2011-07-01

177

Contribution of elastin and collagen to the pathogenesis of monocrotaline induced pulmonary hypertension  

SciTech Connect

Male Sprague-Dawley rats were selected randomly for subcutaneous injections, 24 with monocrotaline (M) (60mg/kg) and 24 with an equivolume of saline, and studied 8, 16 or 28 days later. The right (RV) and left ventricle with septum (LV + S) were separated and weighed. The pulmonary artery (PA) was assessed by light and electron microscopy. Synthesis of elastin collagen and non-collagenous proteins was determined by measuring incorporations of /sup 3/H-valine, /sup 14/C-OH-proline and /sup 14/C-proline respectively. Total content of elastin was determined by weight of residue after CNBr digestion, and of collagen by total OH-proline content in SDS and CNBr extracts. At 16 days, the M injected rats developed a 6-fold increase in PA elastin synthesis and a 2-fold increase in medial wall thickness. Ultrastructural changes included increased microtubules and golgi apparatus in endothelium, decreased proportion of mature elastin in subendothelium and increased ground substance in media. By 28 days, M rats showed a progressive increase in PA elastin and collagen synthesis, greater than 20-fold, and in medial wall thickness, 3-fold. This was associated with a 2-fold increase in total elastin in proportion to the increase in PA weight and the development of RV hypertrophy (RV/LV + S increased more than 2-fold). Progressive irreversible pulmonary hypertension induced by M may be related to continuing stimulation of PA elastin and collagen synthesis.

Todorovich, L.; Johnson, D.; Ranger, P.; Keeley, F.; Rabinovitch, M.

1986-03-01

178

Repeated electroacupuncture attenuating of apelin expression and function in the rostral ventrolateral medulla in stress-induced hypertensive rats.  

PubMed

Studies have revealed that apelin is a novel multifunctional peptide implicated both in blood pressure (BP) regulation and cardiac function control. Evidence shows that apelin and its receptor (APJ) in the rostral ventrolateral medulla (RVLM) may play an important role in central BP regulation; however, its role is controversial and very few reports have shown the relationship between acupuncture and apelin. Our study aims to both investigate the apelinergic system role in stress-induced hypertension (SIH) and determine whether acupuncture therapy effects on hypertension involve the apelinergic system in the RVLM. We established the stress-induced hypertensive rat (SIHR) model using electric foot-shock stressors with noise interventions. The expression of both apelin and the APJ receptor in the RVLM neurons was examined by immunohistochemical staining and Western blots. The results showed apelin expression increased remarkably in SIHR while APJ receptor expression showed no significant difference between control and SIHR groups. Microinjection of apelin-13 into the RVLM of control rats or SIHR produced pressor and tachycardic effects. Furthermore, effects induced by apelin-13 in SIHR were significantly greater than those of control rats. In addition, repetitive electroacupuncture (EA) stimulation at the Zusanli (ST-36) acupoint attenuated hypertension and apelin expression in the RVLM in SIHR; it also attenuated the pressor effect elicited by exogenous apelin-13 microinjection in SIHR. The results suggest that augmented apelin in the RVLM was part of the manifestations of SIH; the antihypertensive effects of EA might be associated with the attenuation of apelin expression and function in the RVLM, which might be a novel role for EA in SIH setting. PMID:23751198

Zhang, Cheng-Rong; Xia, Chun-Mei; Jiang, Mei-Yan; Zhu, Min-Xia; Zhu, Ji-Min; Du, Dong-Shu; Liu, Min; Wang, Jin; Zhu, Da-Nian

2013-08-01

179

Endogenous Estrogen Attenuates Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Vasoconstriction and Pulmonary Arterial Smooth Muscle Cells Proliferation  

PubMed Central

Exogenous estrogen was shown to exert various beneficial effects on multiple diseases including hypoxia-induced pulmonary hypertension (HPH). However, the effect of endogenous estrogen on HPH was seldom investigated. In the present study, we explored the protective effects and mechanisms of endogenous estrogen on hypoxia-induced pulmonary hypertension. Male, female, pregnant and ovariectomized rats were housed in a hypoxic condition for 21 days, and then hemodynamic together with morphologic indexes of pulmonary circulation were measured. The right ventricular systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, and arterial remodeling index were significantly elevated after chronic hypoxia exposure. Experimental data showed less severity in female, especially in pregnant rats. In vitro, artery rings of different sex or estrus cycle rats were obtained, and then artery rings experiments were performed to investigate pulmonary vasoconstriction by recording the maximum phase II vasoconstriction. Data showed that the vasoconstriction was milder in proestrus female than diestrus female or male groups, which could be leveled by treating U0126 (a MAPK pathway inhibitor). Pulmonary arterial smooth muscle cells isolated from different sex or estrus cycle rats were cultured in the condition of 2% oxygen for 24 hours, and cell proliferation was evaluated by the [3H]-thymidine incorporation assay. Cells from proestrus rats exhibited lower proliferation than the other groups, which could be countered by both U0126 and raloxifene (a selective estrogen receptor modulator). Serum estradiol levels were detected, and rats with higher levels showed less severity of pulmonary hypertension. Conclusively, endogenous estrogen may alleviate hypoxia-induced pulmonary hypertension by attenuating vasoconstriction through non-genomic mechanisms and inhibiting smooth muscle cells proliferation through both genomic and non-genomic mechanisms. PMID:23630443

Xu, Dunquan; Niu, Wen; Luo, Ying; Zhang, Bo; Liu, Manling; Dong, Haiying; Liu, Yi; Li, Zhichao

2013-01-01

180

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

181

Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring.  

PubMed

Intrauterine undernutrition plays a role in the development of adult hypertension. Most studies are done in male offspring to delineate the mechanisms whereby blood pressure may be raised; however, the vascular mechanisms involved in female offspring are unclear. Female offspring of pregnant Sprague-Dawley rats fed either a control (C; 18%) or a low-protein (LP; 6%) diet during pregnancy were used. Birth weight and later growth were markedly lower in LP than in C offspring. LP offspring exhibited impaired estrous cyclicity with increased mean arterial pressure. Hypotensive response to acetylcholine (ACh) and the hypertensive response to phenylephrine (PE) were greater in LP than in C rats. N-nitro-L-arginine methyl ester (L-NAME) induced greater hypertensive responses in C than in LP rats. Endothelium-intact mesenteric arteries from LP offspring exhibited increased contractile responses to PE and reduced vasodilation in response to ACh. In endothelium-denuded arteries, relaxation responses to sodium nitroprusside were similar in both groups. Basal and ACh-induced increase in vascular nitrite/nitrate production was lower in LP than in C offspring. L-NAME or 1H-1,2,4-oxadiazolo-4,3-quinoxalin-1-one inhibited ACh relaxations and enhanced PE contractions in C offspring, but had minimal effect in LP rats. The decreased NO-mediated vascular response might explain the increased vascular contraction and arterial pressure in female offspring with low birth weight. PMID:18957856

Sathishkumar, Kunju; Elkins, Rebekah; Yallampalli, Uma; Yallampalli, Chandra

2009-01-01

182

TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension  

E-print Network

of metalloproteinases (TIMPs) inhibits matrix metalloproteinases (MMPs) that degrade the matrix structural proteins with doxycycline, a matrix metalloproteinase inhibi- tor, improved matrix integrity in mesenteric and carotid. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Tissue inhibitor of metalloproteinase Hypertension Vascular remodelling Extracellular matrix 1

MacMillan, Andrew

183

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

2002-01-01

184

Human immunodeficiency virus-1 transgene expression increases pulmonary vascular resistance and exacerbates hypoxia-induced pulmonary hypertension development  

PubMed Central

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial resistance and vessel remodeling. Patients living with human immunodeficiency virus-1 (HIV-1) have an increased susceptibility to develop severe pulmonary hypertension (PH) irrespective of their CD4+ lymphocyte counts. While the underlying cause of HIV-PAH remains unknown, the interaction of HIV-1 proteins with the vascular endothelium may play a critical role in HIV-PAH development. Hypoxia promotes PH in experimental models and in humans, but the impact of HIV-1 proteins on hypoxia-induced pulmonary vascular dysfunction and PAH has not been examined. Therefore, we hypothesize that the presence of HIV-1 proteins and hypoxia synergistically augment the development of pulmonary vascular dysfunction and PH. We examined the effect of HIV-1 proteins on pulmonary vascular resistance by measuring pressure-volume relationships in isolated lungs from wild-type (WT) and HIV-1 Transgenic (Tg) rats. WT and HIV-1 Tg rats were exposed to 10% O2 for four weeks to induce experimental pulmonary hypertension to assess whether HIV-1 protein expression would impact the development of hypoxia-induced PH. Our results demonstrate that HIV-1 protein expression significantly increased pulmonary vascular resistance (PVR). HIV-1 Tg mice demonstrated exaggerated pulmonary vascular responses to hypoxia as evidenced by greater increases in right ventricular systolic pressures, right ventricular hypertrophy and vessel muscularization when compared to wild-type controls. This enhanced PH was associated with enhanced expression of HIF-1? and PCNA. In addition, in vitro studies reveal that medium from HIV-infected monocyte derived macrophages (MDM) potentiates hypoxia-induced pulmonary artery endothelial proliferation. These results indicate that the presence of HIV-1 proteins likely impact pulmonary vascular resistance and exacerbate hypoxia-induced PH. PMID:23662175

Porter, Kristi M.; Walp, Erik R.; Elms, Shawn C.; Raynor, Robert; Mitchell, Patrick O.; Guidot, David M.; Sutliff, Roy L.

2013-01-01

185

[The activity of 11beta-hydroxysteroid dehydrogenase of rat kidney and liver at inherited stress-induced arterial hypertension].  

PubMed

11beta-hydroxysteroid dehydrogenase (11beta-HSD) is the key enzyme of glucocorticoid metabolism, which catalyzes interconversion of corticosterone and 11-dehydrocorticosterone in rat. The activity of 11beta-HSD in kidneys of rats with inherited stress-induced arterial hypertension (ISIAH) was significantly (p < 0.05) higher than that in WAG rats. The opposite was observed in the activity of liver 11beta-HSD. Under stress condition no changes in the kidney 11beta-HSD activity of both strains were observed, but the liver 11beta-HSD activity in ISIAH rats was significantly (p < 0.05) higher as compared to basal level and stressed WAG rats. It is possible that the features of the 11beta-HSD activity in ISIAH rats may reflect the hypertensive status of ISIAH rats. PMID:17288248

Cherkasova, O P

2006-01-01

186

Emblica officinalis exerts antihypertensive effect in a rat model of DOCA-salt-induced hypertension: role of (p) eNOS, NO and oxidative stress.  

PubMed

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone acetate/1% NaCl high salt (DOCA/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may influence DOCA/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced in rats by DOCA-salt (20 mg/kg, s.c.) twice weekly for 5 weeks and replacing drinking water with 1% NaCl solution. These rats received cotreatment of different doses of EO (75, 150 and 300 mg/kg/day) for 5 weeks. EO significantly decreased arterial blood pressure and heart rate along with cardiac and renal hypertrophy in a dose-dependent fashion as compared to DOCA control rats. Increased TBARS and decreased endogenous antioxidants including GSH, SOD and GSHPx activity in serum, heart and kidney tissues of hypertensive rats were also normalized. Furthermore, this antihypertensive activity of EO was also linked with increased serum NO, K(+) levels and decreased Na(+) levels. Moreover, EO robustly increased activated eNOS expression in heart. Our results demonstrate that EO reduces oxidative stress, prevents development and progression of hypertension as well as cardiac and renal hypertrophy in DOCA/HS-induced hypertension via modulation of activated eNOS, endogenous antioxidants, serum NO and electrolyte levels. PMID:21748534

Bhatia, Jagriti; Tabassum, Fauzia; Sharma, Ashok Kumar; Bharti, Saurabh; Golechha, Mahaveer; Joshi, Sujata; Sayeed Akhatar, Md; Srivastava, Abhay Krishna; Arya, Dharamvir Singh

2011-09-01

187

Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice.  

PubMed

Pulmonary arterial hypertension (PAH) is a life?threatening disease characterized by the complex proliferation of the pulmonary vascular endothelium and progressive pulmonary vascular remodeling. CD4+CD25+ regulatory T cells (Tregs) have been the focus of numerous studies into PAH. The present study aimed to investigate the role and mechanisms of Tregs in hypoxia?induced PAH. A total of 60 male mice were divided at random into three groups: Normoxia group, hypoxia control group and Tregs group. Measurements were obtained of the right ventricle systolic pressure (RVSP) and the Fulton's index; in addition, the mRNA and protein expression of pro?inflammatory cytokines including monocyte chemotactic protein 1 (MCP?1), interleukin (IL)?1? and IL?6, as well as the anti?inflammatory cytokine IL?10 in the lungs were determined by reverse transcription quantitative polymerase chain reaction and western blot analysis in vivo. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic condition with or without Tregs for 48 h, and the proliferation rate and cell cycle of HPASMCs were determined. In addition, the protein levels of phosphorylated (p)?Akt and p?extracellular signal?regulated kinase (ERK) were measured in HPASMCs in vitro. The results showed that Treg treatment significantly reduced the increased the hypoxia?induced RVSP and Fulton's index, decreased pro?inflammatory cytokine expression as well as enhanced IL?10 levels in vivo. Furthermore, Treg treatment significantly reduced HPASMCs proliferation and the expression of cyclin D1, cyclin?dependent kinase (CDK)4, p?Akt and p?ERK, as well as increased p27 expression in vitro. In conclusion, the results of the present study indicated that Tregs protected against hypoxia?induced PAH in mice; the mechanisms of which may proceed via the suppression of the inflammatory response, as Tregs were found to enhance anti?inflammatory cytokine levels, inhibit HPASMCs proliferation and regulate the cell cycle. These results therefore indicated that Tregs may be a potential novel target for the treatment of PAH. PMID:25523119

Chu, Yanbiao; Xiangli, Xiaoying; Xiao, Wei

2015-04-01

188

Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide.  

PubMed

The present study tested the hypotheses that 1) nitric oxide (NO) is involved in attenuated responses to ANG II in female mice, and 2) there is differential expression of neuronal NO synthase (nNOS) in the subfornical organ (SFO) and paraventricular nucleus (PVN) in response to systemic infusions of ANG II in males vs. females. Aortic blood pressure (BP) was measured in conscious mice with telemetry implants. N(G)-nitro-l-arginine methyl ester (l-NAME; 100 microg x kg(.-1)day(-1)), an inhibitor of NOS, was administrated into the lateral cerebral ventricle for 14 days before and during ANG II pump implantation. Central infusion of l-NAME augmented the pressor effects of systemic ANG II in females (Delta21.5 + or - 2.2 vs. Delta9.2 + or - 1.5 mmHg) but not in males (Delta29.4 + or - 2.5 vs. Delta30.1 + or - 2.5 mmHg). Central administration of N(5)-(1-imino-3-butenyl)-l-ornithine (l-VNIO), a selective nNOS inhibitor, also significantly potentiated the increase in BP induced by ANG II in females (Delta17.5 + or - 3.2 vs. Delta9.2 + or - 1.5 mmHg). In gonadectomized mice, central l-NAME infusion did not affect the pressor response to ANG II in either males or females. Ganglionic blockade after ANG II infusion resulted in a greater reduction in BP in central l-NAME- or l-VNIO-treated females compared with control females. Western blot analysis of nNOS protein expression indicated that levels were approximately 12-fold higher in both the SFO and PVN of intact females compared with those in intact males. Seven days of ANG II treatment resulted in a further increase in nNOS protein expression only in intact females (PVN, to approximately 51-fold). Immunohistochemical studies revealed colocalization of nNOS and estrogen receptors in the SFO and PVN. These results suggest that NO attenuates the increase in BP induced by ANG II through reduced sympathetic outflow in females and that increased nNOS protein expression associated with the presence of female sex hormones plays a protective role against ANG II-induced hypertension in female mice. PMID:19734362

Xue, Baojian; Singh, Minati; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

2009-11-01

189

Endocannabinoid-mediated modulation of Gq/11 protein-coupled receptor signaling-induced vasoconstriction and hypertension.  

PubMed

Activation of G protein-coupled receptors (GPCRs) can induce vasoconstriction via calcium signal-mediated and Rho-dependent pathways. Earlier reports have shown that diacylglycerol produced during calcium signal generation can be converted to an endocannabinoid, 2-arachidonoylglycerol (2-AG). Our aim was to provide evidence that GPCR signaling-induced 2-AG production and activation of vascular type1 cannabinoid receptors (CB1R) is capable of reducing agonist-induced vasoconstriction and hypertension. Rat and mouse aortic rings were examined by myography. Vascular expression of CB1R was demonstrated with immunohistochemistry. Rat aortic vascular smooth muscle cells (VSMCs) were cultured for calcium measurements and 2-AG-determination. Inhibition or genetic loss of CB1Rs enhanced vasoconstriction induced by angiotensin II (AngII) or phenylephrine (Phe), but not by prostaglandin(PG)F2?. AngII-induced vasoconstriction was augmented by inhibition of diacylglycerol lipase (tetrahydrolipstatin) and was attenuated by inhibition of monoacylglycerol lipase (JZL184) suggesting a functionally relevant role for endogenously produced 2-AG. In G?q/11-deficient mice vasoconstriction was absent to AngII or Phe, which activate Gq/11-coupled receptors, but was maintained in response to PGF2?. In VSMCs, AngII-stimulated 2-AG-formation was inhibited by tetrahydrolipstatin and potentiated by JZL184. CB1R inhibition increased the sustained phase of AngII-induced calcium signal. Pharmacological or genetic loss of CB1R function augmented AngII-induced blood pressure rise in mice. These data demonstrate that vasoconstrictor effect of GPCR agonists is attenuated via Gq/11-mediated vascular endocannabinoid formation. Agonist-induced endocannabinoid-mediated CB1R activation is a significant physiological modulator of vascular tone. Thus, the selective modulation of GPCR signaling-induced endocannabinoid release has a therapeutic potential in case of increased vascular tone and hypertension. PMID:25595485

Szekeres, Mária; Nádasy, György L; Turu, Gábor; Soltész-Katona, Eszter; Benyó, Zoltán; Offermanns, Stefan; Ruisanchez, Éva; Szabó, Eszter; Takáts, Zoltán; Bátkai, Sándor; Tóth, Zsuzsanna E; Hunyady, László

2015-03-01

190

Angiotensin II-induced hypertension in bradykinin B2 receptor knockout mice.  

PubMed

The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)-induced hypertension in mice. BK B2receptor knockout (B2R-/-) and wild-type (B2R+/+) mice (22to 26 g) were infused with either saline (SAL) or Ang II (40ng/min) via an osmotic minipump implanted intraperitoneally. On day 12after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B2R+/+ and SAL/B2R-/- mice(128+/-5 versus 133+/-6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B2R-/- than in Ang II/B2R+/+ mice (173+/-6versus 156+/-5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP)was also higher in anesthetized Ang II/B2R-/- mice than in Ang II/B2R+/+mice (139+/-3 versus 124+/-3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45ng/min) caused equivalent increases in SBP in B2R+/+ and B2R-/- mice measured on day 12 after implantation (151+/-4 versus 149+/-5 mm Hg, n=9and 8). MAP also did not differ on day 13 after implantation between NE/B2R+/+ and NE/B2R-/- mice (120+/-6 versus 122+/-4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B2R-/- mice than in Ang II/B2R+/+ mice (2.34+/-0.06 versus 4.33+/-0.19 mL x min-1 x g-1; P<0.05). Acute inhibition of NO synthase (NOS)with nitro-L-arginine-methyl ester (0.5 microg x g-1 x min-1) in SAL/B2+/+ and SAL/B2-/- mice caused equal increases in MAP (142+/-1 versus 145+/-1 mmHg) and decreases in RPF (2.06+/-0.06 versus 2.12+/-0.15 mL x min-1 x g-1).However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B2R+/+ mice than of Ang II/B2R-/- mice, such that MAP after NOS inhibition in Ang II/B2R+/+ approached that of Ang II/B2R-/- mice (156+/-2versus 159+/-2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B2R+/+ mice to values similar to those of Ang II/B2R-/- mice before NOS inhibition (2.12+/-0.09 versus 2.34+/-0.06 mL x min-1 x g-1). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B2R-/- mice to Ang II-induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins. PMID:11270390

Cervenka, L; Maly, J; Karasová, L; Simová, M; Vítko, S; Hellerová, S; Heller, J; El-Dahr, S S

2001-03-01

191

Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension  

PubMed Central

Background Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling. Methods and Results Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO2 = 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-?, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media. Conclusion Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ. PMID:16171515

Kwapiszewska, Grazyna; Wilhelm, Jochen; Wolff, Stephanie; Laumanns, Isabel; Koenig, Inke R; Ziegler, Andreas; Seeger, Werner; Bohle, Rainer M; Weissmann, Norbert; Fink, Ludger

2005-01-01

192

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

193

New models of pulmonary hypertension based on VEGF receptor blockade-induced endothelial cell apoptosis  

PubMed Central

In spite of treatment, severe angioproliferative pulmonary arterial hypertension (PAH) remains a disease characterized by great morbidity and shortened survival. New treatment strategies for patients with PAH are needed, and after drug development, preclinical studies are best conducted in animal models which present with pulmonary angio-obliterative disease and right heart failure. A rat model of severe pulmonary hypertension and right heart failure, described a decade ago, continues to be investigated and provide insight into the nature of the lung vascular lesions and mechanisms of cardiac adaptation to an altered lung circulation. This rat model is based on the combination of VEGF receptor blockade with Su5416 and chronic hypoxia; use of this pulmonary hypertension induction strategy led to developing the concept of apoptosis-dependent compensatory vascular cell growth. Although, often employed in experimental designs, chronic hypoxia is not necessary for the development of angio-obliterative pulmonary hypertension. Left pneumonectomy combined with Su5416 also results in severe pulmonary hypertension in normoxic conditions. Similarly, the immune insufficiency component of severe PAH can be modeled in athymic rats (lacking T-lymphocytes). In these rats housed under normoxic conditions, treatment with the VEGFR receptor blocker results in angioproliferative pulmonary hypertension; cardiopulmonary disease in these animals can be prevented by immune reconstitution of regulatory T-cells (Tregs). Finally, chronic hypoxia can be replaced with another stimulator of HIF-1?: Ovalbumin (Ova). Immunization of rats with Ova increases lung tissue HIF-1? protein expression, and in Su5416-treated rats causes lethal pulmonary hypertension. Finally, we postulate that these models may also be useful for “reverse translation”; that is, the mechanisms of lung vascular cell death and growth and the modifying influences of immune and bone marrow cells that have been identified in the Su5416 VEGFR inhibitor models can be informative about heretofore undescribed processes in human PAH. PMID:23372927

Nicolls, Mark R.; Mizuno, Shiro; Taraseviciene-Stewart, Laima; Farkas, Laszlo; Drake, Jennnifer I.; Al Husseini, Aysar; Gomez-Arroyo, Jose G.; Voelkel, Norbert F.; Bogaard, Herman J.

2012-01-01

194

Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms  

Microsoft Academic Search

Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms\\u000a are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure\\u000a even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased\\u000a plasmatic nitric oxide levels and with a dysregulation

Denise Grotto; Michele M. de Castro; Gustavo R. M. Barcelos; Solange C. Garcia; Fernando Barbosa Jr

2009-01-01

195

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

196

Role of the NADPH oxidases in the subfornical organ in angiotensin II-induced hypertension.  

PubMed

Reactive oxygen species and the NADPH oxidases contribute to hypertension via mechanisms that remain undefined. Reactive oxygen species produced in the central nervous system have been proposed to promote sympathetic outflow, inflammation, and hypertension, but the contribution of the NADPH oxidases to these processes in chronic hypertension is uncertain. We therefore sought to identify how NADPH oxidases in the subfornical organ (SFO) of the brain regulate blood pressure and vascular inflammation during sustained hypertension. We produced mice with loxP sites flanking the coding region of the NADPH oxidase docking subunit p22(phox). SFO-targeted injections of an adenovirus encoding cre-recombinase markedly diminished p22(phox), Nox2, and Nox4 mRNA in the SFO, as compared with a control adenovirus encoding red-fluorescent protein injection. Increased superoxide production in the SFO by chronic angiotensin II infusion (490 ng/kg min(-1) × 2 weeks) was blunted in adenovirus encoding cre-recombinase-treated mice, as detected by dihydroethidium fluorescence. Deletion of p22(phox) in the SFO eliminated the hypertensive response observed at 2 weeks of angiotensin II infusion compared with control adenovirus encoding red-fluorescent protein-treated mice (mean arterial pressures=97 ± 15 versus 154 ± 6 mm Hg, respectively; P=0.0001). Angiotensin II infusion also promoted marked vascular inflammation, as characterized by accumulation of activated T-cells and other leukocytes, and this was prevented by deletion of the SFO p22(phox). These experiments definitively identify the NADPH oxidases in the SFO as a critical determinant of the blood pressure and vascular inflammatory responses to chronic angiotensin II, and further support a role of reactive oxygen species in central nervous system signaling in hypertension. PMID:23248154

Lob, Heinrich E; Schultz, David; Marvar, Paul J; Davisson, Robin L; Harrison, David G

2013-02-01

197

Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF.  

PubMed

This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan significantly ameliorated left ventricular ischemia and prevented the development of cardiac hypertrophy and fibrosis in DS rats. The benefits were associated with the attenuation of oxidative stress, normalization of myocardial capillary density and inhibition of capillary endothelial apoptosis. Moreover, DS rats with significant cardiac hypertrophy and fibrosis displayed decreased myocardial vascular endothelial growth factor (VEGF) expression and increased cardiac apoptosis signal-regulating kinase 1 (ASK1) activation. Treatment with irbesartan significantly reversed these phenotypes. Tempol treatment of DS rats mimicked all the above-mentioned effects of irbesartan, indicating the critical role of oxidative stress in cardiac injury. We also investigated the role of VEGF and ASK1 in oxidative stress-induced endothelial apoptosis by using cultured endothelial cells from wild-type and ASK1-deficient mice. Oxidative stress-induced ASK1 activation led to endothelial apoptosis, and VEGF treatment prevented oxidative stress-induced endothelial apoptosis by inhibiting ASK1 activation. We obtained the first evidence that oxidative stress-induced cardiac VEGF repression and ASK1 activation caused the enhancement of endothelial apoptosis and contributed to a decrease in myocardial capillary density. These effects resulted in angiotensin II-induced progression of cardiac injury. PMID:22089532

Nako, Hisato; Kataoka, Keiichiro; Koibuchi, Nobutaka; Dong, Yi-Fei; Toyama, Kensuke; Yamamoto, Eiichiro; Yasuda, Osamu; Ichijo, Hidenori; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2012-02-01

198

Attenuation of stress-induced hypertension by exercise independent of training effects: An animal model  

Microsoft Academic Search

The present study attempted to determine if exercise, in the absence of physical training, could alter development of hypertension during chronic exposure to a psychosocial stressor. Two groups of genetically normotensive rats were exposed to social stress for 7 days, following 5 weeks of acclimation to social isolation. One group had access to exercise in a running wheel during the

David E. Mills; Ron P. Ward

1986-01-01

199

Strain-dependent differences of restraint stress-induced hypertension in WKY and SHR  

Microsoft Academic Search

The aim of our study was to investigate differences in restraint stress-response between normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) and the consequences for tail-cuff (TC) blood pressure measurements. We therefore radiotelemetrically collected cardiovascular data from WKY and SHR that underwent TC procedures and measured plasma norepinephrine (NE) and angiotensin II (ATII) levels as well as gene

Alexander Grundt; Christina Grundt; Stefan Gorbey; Martin A. Thomas; Björn Lemmer

2009-01-01

200

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

201

MODULATION OF STRESS INDUCED BY ISOMETRIC HANDGRIP TEST IN HYPERTENSIVE PATIENTS FOLLOWING YOGIC RELAXATION TRAINING  

Microsoft Academic Search

Abstract : Abstract : Abstract : Abstract : 13 essential hypertensive patients aged 41 to 60 years were given yoga training for 60 min daily, Monday through Saturday, for a total duration of 4 weeks. Blood pressure and heart rate (HR) were measured with non-invasive semi-automatic blood pressure monitor. Measurements were recorded before the training and at weekly intervals during

BHAVANANI MADANMOHAN; ASMITA PATIL; KUMAR BABU

202

Exercise Training Restores Hypertension-Induced Changes in the Elastic Tissue of the Thoracic Aorta  

Microsoft Academic Search

Background\\/Aims: Pharmacological antihypertensive therapies decrease both wall hypertrophy and collagen, but are unable to diminish the elastic content in the thoracic aorta. We investigated the effects of exercise training on aortic structure and function. Methods: Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), submitted to low-intensity training (T) or kept sedentary (S), were subjected to haemodynamic analyses. The thoracic aorta

Maria Tereza Jordão; Fernando V. L. Ladd; Antonio Augusto Coppi; Renato P. Chopard; Lisete C. Michelini

2011-01-01

203

Prenatal Testosterone Exposure Induces Hypertension in Adult Females via Androgen Receptor-Dependent Protein Kinase C?-Mediated Mechanism.  

PubMed

Prenatal exposure to excess testosterone induces hyperandrogenism in adult females and predisposes them to hypertension. We tested whether androgens induce hypertension through transcriptional regulation and signaling of protein kinase C (PKC) in the mesenteric arteries. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate (0.5 mg/kg per day from gestation days 15 to 19, SC) and their 6-month-old adult female offspring were examined. Plasma testosterone levels (0.84±0.04 versus 0.42±0.09 ng/mL) and blood pressures (111.6±1.3 versus 104.5±2.4 mm?Hg) were significantly higher in prenatal testosterone-exposed rats compared with controls. This was accompanied with enhanced expression of PKC? mRNA (1.5-fold) and protein (1.7-fold) in the mesenteric arteries of prenatal testosterone-exposed rats. In addition, mesenteric artery contractile responses to PKC activator, phorbol-12,13-dibutyrate, was significantly greater in prenatal testosterone-exposed rats. Treatment with androgen receptor antagonist flutamide (10 mg/kg, SC, BID for 10 days) significantly attenuated hypertension, PKC? expression, and the exaggerated vasoconstriction in prenatal testosterone-exposed rats. In vitro exposure of testosterone to cultured mesenteric artery smooth muscle cells dose dependently upregulated PKC? expression. Analysis of PKC? gene revealed a putative androgen responsive element in the promoter upstream to the transcription start site and an enhancer element in intron-1. Chromatin immunoprecipitation assays showed that androgen receptors bind to these elements in response to testosterone stimulation. Furthermore, luciferase reporter assays showed that the enhancer element is highly responsive to androgens and treatment with flutamide reverses reporter activity. Our studies identified a novel androgen-mediated mechanism for the control of PKC? expression via transcriptional regulation that controls vasoconstriction and blood pressure. PMID:25489059

Blesson, Chellakkan S; Chinnathambi, Vijayakumar; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

2014-12-01

204

An afferent vagal nerve pathway links hepatic PPARalpha activation to glucocorticoid-induced insulin resistance and hypertension.  

PubMed

Glucocorticoid excess causes insulin resistance and hypertension. Hepatic expression of PPARalpha (Ppara) is required for glucocorticoid-induced insulin resistance. Here we demonstrate that afferent fibers of the vagus nerve interface with hepatic Ppara expression to disrupt blood pressure and glucose homeostasis in response to glucocorticoids. Selective hepatic vagotomy decreased hyperglycemia, hyperinsulinemia, hepatic insulin resistance, Ppara expression, and phosphoenolpyruvate carboxykinase (PEPCK) enzyme activity in dexamethasone-treated Ppara(+/+) mice. Selective vagotomy also decreased blood pressure, adrenergic tone, renin activity, and urinary sodium retention in these mice. Hepatic reconstitution of Ppara in nondiabetic, normotensive dexamethasone-treated PPARalpha null mice increased glucose, insulin, hepatic PEPCK enzyme activity, blood pressure, and renin activity in sham-operated animals but not hepatic-vagotomized animals. Disruption of vagal afferent fibers by chemical or surgical means prevented glucocorticoid-induced metabolic derangements. We conclude that a dynamic interaction between hepatic Ppara expression and a vagal afferent pathway is essential for glucocorticoid induction of diabetes and hypertension. PMID:17276352

Bernal-Mizrachi, Carlos; Xiaozhong, Liu; Yin, Li; Knutsen, Russell H; Howard, Michael J; Arends, Joop J A; Desantis, Pascual; Coleman, Trey; Semenkovich, Clay F

2007-02-01

205

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

206

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

PubMed

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

2011-11-01

207

Analysis of differentially expressed genes in cold-exposed mice to investigate the potential causes of cold-induced hypertension  

PubMed Central

Cold exposure is considered to be an important contributing factor to the high morbidity of hypertension. In order to elucidate the cause and mechanism of cold-induced hypertension (CIH), gene expression analysis was performed on microarray data for two groups of cold-exposed mice (4°C for 1 week and 4°C for 5 weeks, three replicates per group) and their respective control groups maintained at 30°C. Analysis results indicated that the differentially expressed genes with the most significance were associated with adaptive thermogenesis, fatty acid metabolism and energy metabolism. The expected marked increase in metabolism during cold exposure caused tissue hypoxia. Genes involved in the hypoxia-inducible factor signaling pathway were activated. In addition, genes associated with oxidative stress were significantly upregulated, including superoxide dismutase 2 (SOD2) and epoxide hydrolase 2 (EPHX2). The majority of genes involved in inflammation-associated pathways were shown to be downregulated in the 4°C 5-week group. Therefore, the results of the present study indicate that tissue hypoxia and increased oxidative stress may play important roles in the process of CIH. PMID:24944607

TUO, BUXIONG; LI, CHAOMIN; PENG, LIJING; YE, MINGXIA; LIU, WEI; ZHONG, XIAOLAN; LI, HUI

2014-01-01

208

Analysis of differentially expressed genes in cold-exposed mice to investigate the potential causes of cold-induced hypertension.  

PubMed

Cold exposure is considered to be an important contributing factor to the high morbidity of hypertension. In order to elucidate the cause and mechanism of cold-induced hypertension (CIH), gene expression analysis was performed on microarray data for two groups of cold-exposed mice (4°C for 1 week and 4°C for 5 weeks, three replicates per group) and their respective control groups maintained at 30°C. Analysis results indicated that the differentially expressed genes with the most significance were associated with adaptive thermogenesis, fatty acid metabolism and energy metabolism. The expected marked increase in metabolism during cold exposure caused tissue hypoxia. Genes involved in the hypoxia-inducible factor signaling pathway were activated. In addition, genes associated with oxidative stress were significantly upregulated, including superoxide dismutase 2 (SOD2) and epoxide hydrolase 2 (EPHX2). The majority of genes involved in inflammation-associated pathways were shown to be downregulated in the 4°C 5-week group. Therefore, the results of the present study indicate that tissue hypoxia and increased oxidative stress may play important roles in the process of CIH. PMID:24944607

Tuo, Buxiong; Li, Chaomin; Peng, Lijing; Ye, Mingxia; Liu, Wei; Zhong, Xiaolan; Li, Hui

2014-07-01

209

Effect of palm oil on oxidative stress-induced hypertension in sprague-dawley rats  

Microsoft Academic Search

BackgroundOxidative stress, associated with increased plasma isoprostane (ISO) and reductions in plasma glutathione (GSH), has been shown to cause severe hypertension in normal rats. Palm oil (PO), with an unsaturated-to-saturated fatty acid ratio close to one and rich in antioxidant vitamins, has been investigated for its beneficial effects on arterial thrombosis and atherosclerosis. In this study, the effect of PO

Agaba A. Ganafa; Robin R. Socci; Danita Eatman; Natalia Silvestrov; Imad K. Abukhalaf; Mohamed A. Bayorh

2002-01-01

210

Chronic local cold stress to the soles induces hypertension in rats  

Microsoft Academic Search

The purpose of this study was to determine whether cold-stress stimulation to the soles of paws produces continuous hypertension in rats. Wistar–Kyoto rats were kept in cages with a 0°C floor and 23°C room temperature (cold-stressed group, n = 10) or in cages with 23°C floor and 23°C room temperature (control group, n = 10). BP and levels of plasma

Naohiro Kanayama; Selina Khatun; Hossain Belayet; Liping She; Toshihiko Terao

1999-01-01

211

Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats.  

PubMed

The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain barrier (BBB) integrity and the activity of astrocytes during the Nw-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-a, IL-1b, and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zonula occludens-1 and occludin, and glial fibrillary acidic protein, by using immunohisto-chemical method. The serum levels of TNF-a, IL-1 IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p<.01). The EB dye extravasation increased in cerebellum (p<.001) and diencephalon (p<.05) of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye extravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p<.001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-1 and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining was seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study indicates that, in L-NAME hypertensive rats, ANG II leads to an increase in the extravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes. PMID:15763998

Ahishali, B; Kaya, M; Kalayci, R; Uzun, H; Bilgic, B; Arican, N; Elmas, I; Aydin, S; Kucuk, M

2005-02-01

212

High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction  

PubMed Central

Basement membrane degradation and blood-brain barrier damage appear after cerebral infarction, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke-prone spontaneously hypertensive rats by intragastric administration of high-sodium water (1.3% NaCl) for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone spontaneously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregulation is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodium water-induced focal cerebral infarction. PMID:25206775

Hou, Huilian; Zhang, Guanjun; Wang, Hongyan; Gong, Huilin; Wang, Chunbao; Zhang, Xuebin

2014-01-01

213

Effects of lisinopril on NMDA receptor subunits 2A and 2B levels in the hippocampus of rats with L-NAME-induced hypertension.  

PubMed

Hypertension is major risk factor leading to cerebrovascular pathologies. N-methyl D-aspartate receptors (NMDARs) and renin-angiotensin system are involved in neuronal plasticity, as well as cognitive functions in the hippocampus. In this study, we examined the effects of lisinopril, an ACE inhibitor, on the levels of hippocampal NMDAR subunits; NR2A and NR2B in L-NAME (N(?)-nitro-L-arginine Methyl Ester)-induced hypertensive rats. In addition, malondialdehyde (MDA) levels were measured as a marker for lipid peroxidation. Compared with the control group, the MDA level was significantly increased after 8 weeks in the L-NAME-treated group. Rats treated with lisinopril and L-NAME plus lisinopril were found to have significantly decreased hippocampal MDA levels. Regarding the hippocampal concentrations of NR2A and NR2B, there were no statistically significant differences between groups. We demonstrated that lisinopril treatment has no direct regulatory effect on the levels of NR2A and NR2B in the rat hippocampus. Our results showed that Lisinopril could act as an antioxidant agent against hypertension-induced oxidative stress in rat hippocampus. The findings support that the use of lisinopril may offer a good alternative in the treatment of hypertension by reducing not only blood pressure but also prevent hypertensive complications in the brain. PMID:22943192

Sutcu, Recep; Kirbas, Aynur; Kirbas, Serkan; Kutluhan, Suleyman; Delibas, Namik

2012-10-01

214

Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats  

PubMed Central

Background Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ) in L-NAME-induced hypertensive rats. Methods The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg) administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg). For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day) plus the vehicle or L-NAME (40 mg/kg/day) in combination with captopril (20 mg/kg/day) or MECZ (300 mg/kg/day) and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. Results Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg) to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%), total cholesterol (32.1%) and LDL-cholesterol (75.3%) while increasing that of HDL-cholesterol (58.4%) with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group). Conclusion MECZ possesses antihypertensive and organ protective effects that may result from its ability to increase the production of the endogenous NO and/or to regulate dyslipidemia. PMID:23368533

2013-01-01

215

Cytochrome P4501A1 is Required for Vascular Dysfunction and Hypertension Induced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin  

Technology Transfer Automated Retrieval System (TEKTRAN)

National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAH). Further, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (...

216

Low protein diet exacerbates NO synthase inhibitor-induced hypertension in rats  

Microsoft Academic Search

Background. A low-protein diet (LPD) may suppress nitric oxide (NO) production through the reduction of L-arginine intake, and possibly\\u000a exacerbates hypertension under certain conditions. We examined the effect of LPD on blood pressure in rats that received a\\u000a low dose of an inhibitor of nitric oxide synthesis.\\u000a \\u000a \\u000a Methods. Were compared tail-cuff pressure (TCP), urinary nitrite and nitrate (NO2\\/NO3) excretion, and

Hiromichi Kumagai; Yoshiko Kikuchi; Noriko Kumeta; Masato Kimura; Toshio Sakai

1999-01-01

217

Paradoxical effects of streptozotocin-induced diabetes on endothelial dysfunction in stroke-prone spontaneously hypertensive rats  

PubMed Central

Abstract Although both diabetes and hypertension are risk factors for cardiovascular disease, the role of hyperglycaemia per se in endothelial dysfunction is controversial. This study was designed to examine whether hyperglycaemia, or streptozotocin-induced diabetes, could aggravate endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHRSP). Hyperglycaemia was induced by streptozotocin in 2-month-old SHRSP and age-matched normotensive Wistar–Kyoto (WKY) rats. The aorta was isolated 8 weeks after induction of hyperglycaemia to record its function and to examine its morphology with transmission electron microscopy. Endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive haem oxygenase (HO-1/HO-2) levels were determined with Western blotting. Aortic endothelial function and production of reactive oxygen species and nitric oxide were assayed after incubation in vitro in hyperglycaemic, hyperosmolar solution. Streptozotocin-induced diabetes of 8 weeks duration did not result in endothelial dysfunction in normotensive WKY rats. In contrast, hyperglycaemic WKY rats showed significantly enhanced endothelium-dependent vasodilatation, which was abrogated by simultaneous blocking of NOS and HO. The enhanced vasodilatation was associated with elevation of vascular eNOS and HO-1. Significant endothelial dysfunction and massive macrophage–monocyte infiltration were found in SHRSP aorta (the ratio of the number of macrophages to endothelial cells in the intima, expressed as a percentage, was 20.9 ± 2.8% in SHRSP versus 1.9 ± 0.5% in WKY rats, P < 0.01), which was attenuated significantly in hyperglycaemic SHRSP (11.3 ± 1.6%, P < 0.01 versus SHRSP). Acute hyperglycaemia (10 min) aggravated endothelial dysfunction in SHRSP, with a marked increase in intracellular reactive oxygen species and NO production. Sustained in vitro incubation in hyperglycaemic/hyperosmolar conditions (addition of an extra 50 mmol L?1 of glucose or mannitol to the usual buffer, to produce a final osmolarity of 350 mosmol L?1) for 5 h enhanced endothelium-dependent vasodilatation, with elevated vessel NO production and upregulation of eNOS/HO-1 proteins. Sustained hyperglycaemia does not aggravate endothelial dysfunction and macrophage infiltration in SHRSP. Hyperglycaemia/hyperosmolarity-induced upregulation of eNOS and HO-1 may play a role in this paradoxical adaptation of endothelial function. PMID:21930604

Zhong, Mei-Fang; Shen, Wei-Li; Wang, Jian; Yang, Jie; Yuan, Wen-Jun; He, Jin; Wu, Ping-Ping; Wang, Yuan; Zhang, Lan; Higashino, Hideaki; Chen, Hong

2011-01-01

218

Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species.  

PubMed

It has been shown that reactive oxygen species (ROS) contribute to the central effect of ANG II on blood pressure (BP). Recent studies have implicated an antihypertensive action of estrogen in ANG II-infused female mice. The present study used in vivo telemetry recording and in vitro living mouse brain slices to test the hypothesis that the central activation of estrogen receptors in male mice inhibits ANG II-induced hypertension via the modulation of the central ROS production. In male wild-type mice, the systemic infusion of ANG II induced a significant increase in BP (Delta30.1 +/- 2.5 mmHg). Either central infusion of Tempol or 17beta-estradiol (E2) attenuated the pressor effect of ANG II (Delta10.9 +/- 2.3 and Delta4.5 +/- 1.4 mmHg), and the protective effect of E2 was prevented by the coadministration of an estrogen receptor, antagonist ICI-182780 (Delta23.6 +/- 3.1 mmHg). Moreover, the ganglionic blockade on day 7 after the start of ANG II infusions resulted in a smaller reduction of BP in central Tempol- and in central E2-treated males, suggesting that estrogen inhibits the central ANG II-induced increases in sympathetic outflow. In subfornical organ slices, the application of ANG II resulted in a 21.5 +/- 2.5% increase in ROS production. The coadministration of irbesartan, an ANG II type 1 receptor antagonist, or the preincubation of brain slices with Tempol blocked ANG II-induced increases in ROS production (-1.8 +/- 1.6% and -1.0 +/- 1.8%). The ROS response to ANG II was also blocked by E2 (-3.2 +/- 2.4%). The results suggest that the central actions of E2 are involved in the protection from ANG II-induced hypertension and that estrogen modulation of the ANG II-induced effects may involve interactions with ROS production. PMID:18599599

Xue, Baojian; Zhao, Yuanzi; Johnson, Alan Kim; Hay, Meredith

2008-09-01

219

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

220

Concentration-effect relationship of l-propranolol and metoprolol in spontaneous hypertensive rats after exercise-induced tachycardia.  

PubMed

The concentration-effect relationship of l-propranolol and dl-metoprolol were investigated in spontaneous hypertensive rats using reduction in exercise-induced tachycardia as a pharmacodynamic endpoint. The influence of protein binding on the effect relationship was also assessed. The rats were assigned to treatment or placebo groups, where each group received three randomly selected consecutively increasing steady-state infusions. Different pharmacodynamic effect models were fitted to the data, using nonlinear mixed effect modeling. The data were best described by a combined effect model, with a sum of an ordinary Imax and a linear model. At the lower concentration range, the ordinary Imax model dominated, although at higher concentrations, the effect was linearly related to the antagonist concentration. The Imax were 83 +/- 6 and 103 +/- 6 beats . min-1 and the IC50 were 18.1 +/- 4.3 and 50.6 +/- 15.2 ng/ml for l-propranolol and dl-metoprolol, respectively. The slope in the linear model was steeper for l-propranolol than for dl-metoprolol, 28.9 +/- 2.8 and 4.48 +/- 0.39 beats . ml . (min . microgram)-1, respectively. Plasma protein binding of l-propranolol was saturable. The unbound IC50 for l-propranolol was 1.14 +/- 0.27 ng/ml. The concentration-effect relationship of l-propranolol was altered at higher plasma concentrations, due to saturable protein binding. The Imax and the linear concentration-effect relationship may be interpreted as a specific beta-antagonist effect and a membrane-stabilizing effect, respectively. Using exercise-induced tachycardia as a pharmacodynamic endpoint, to study the effect of beta-antagonists in spontaneous hypertensive rats, seems to give reliable results and can be a useful model to extrapolate to humans. PMID:9732372

Brynne, L; Karlsson, M O; Paalzow, L K

1998-09-01

221

Water deprivation-induced sodium appetite and differential expression of encephalic c-Fos immunoreactivity in the spontaneously hypertensive rat.  

PubMed

The spontaneously hypertensive rat (SHR) has an intense consumption of NaCl solution. Water deprivation (WD) followed by water intake to satiety induces partial rehydration (PR)-the WD-PR protocol-and sodium appetite. In the present work, WD produced similar water intake and no alterations in arterial pressure among spontaneously hypertensive rat (SHR), Wistar-Kyoto, and Holtzman strains. It also increased the number of cells with positive c-Fos immunoreactivity (Fos-IR) in the lamina terminalis and in the hypothalamic supraoptic (SON) and paraventricular (parvocellular, PVNp) nucleus in these strains. The WD and WD-PR produced similar alterations in all strains in serum osmolality and protein, plasma renin activity, and sodium balance. The SHR ingested about 10 times more 0.3 M NaCl than normotensives strains in the sodium appetite test that follows WD-PR. After WD-PR, the Fos-IR persisted, elevated in the lamina terminalis of all strains but notably in the subfornical organ of the SHR. The WD-PR reversed Fos-IR in the SON of all strains and in the PVNp of SHR. It induced Fos-IR in the area postrema and in the nucleus of the solitary tract (NTS), dorsal raphe, parabrachial (PBN), pre-locus coeruleus (pre-LC), suprachiasmatic, and central amygdalar nucleus of all strains. This effect was bigger in the caudal-NTS, pre-LC, and medial-PBN of SHRs. The results indicate that WD-PR increases cell activity in the forebrain and hindbrain areas that control sodium appetite in the rat. They also suggest that increased cell activity in facilitatory brain areas precedes the intense 0.3 M NaCl intake of the SHR in the sodium appetite test. PMID:20200133

Pereira-Derderian, Daniela T B; Vendramini, Regina C; Menani, José V; De Luca, Laurival A

2010-05-01

222

Androgen-dependent hypertension is mediated by 20-HETE-induced vascular dysfunction: Role of IkappaB kinase  

PubMed Central

Increased vascular synthesis of 20-HETE is associated with increased vascular contraction, endothelial dysfunction and endothelial activation; all are believed to account for 20-HETE pro-hypertensive properties. We previously demonstrated that the 20-HETE-dependent inhibition of NO production is mediated through I?B kinase (IKK) suggesting a cross talk between 20-HETE-mediated endothelial dysfunction and activation. In this study, we examined the temporal relationship among blood pressure, endothelial dysfunction and endothelial activation and the role of IKK in the rat model of androgen-driven 20-HETE-mediated hypertension. In Sprague-Dawley rats treated with 5?-dihydrotestosterone (DHT), renal vascular 20-HETE levels increased by day 2 of treatment from 17.7±2.4 to 57.7±9.7 ng/mg, while blood pressure elevation reached significance by day 3 (132.7±1.7 vs 117.2±0.8 mmHg). In renal interlobar arteries, when compared to vehicle, DHT treatment increased the sensitivity to phenylephrine-induced vasoconstriction by 3.5-fold, decreased acetylcholine-induced vasorelaxation and increased NF-kB activity, all of which were attenuated by treatment with the 20-HETE antagonist, 20-HEDE. Co-treatment with parthenolide, an IKK inhibitor, attenuated the androgen-dependent 20-HETE-mediated elevation in blood pressure (from 133.7±3.1 to 109.8±3.0 mmHg). In addition, parthenolide treatment negated 20-HETE-mediated inhibition of the relaxing response to acetylcholine and 20-HETE-mediated increase in vascular NF-kB activity. These findings suggest that inhibition of IKK attenuates the androgen-dependent 20-HETE-mediated increase in blood pressure by inhibiting both 20-HETE-dependent endothelial activation and dysfunction. PMID:21321301

Wu, Cheng-Chia; Cheng, Jennifer; Zhang, Frank Fan; Gotlinger, Katherine H.; Kelkar, Mukul; Zhang, Yilun; Jat, Jawahar L.; Falck, John R.; Schwartzman, Michal L.

2011-01-01

223

Cimicifuga racemosa impairs fatty acid ?-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension.  

PubMed

The aim of this work was to evaluate the effects of therapeutic doses of Cimicifuga racemosa on cardiovascular parameters and on liver lipid metabolism and redox status in an animal model of estrogen deficiency associated with hypertension, a condition that could make the liver more vulnerable to drug-induced injuries. Female Wistar rats were subjected to the surgical procedures of bilateral ovariectomy (OVX) and induction of renovascular hypertension (two-kidneys, one-clip; 2K1C). These animals (OVX + 2K1C) were treated with daily doses of a C. racemosa extract, using a dose that is similar to that recommended to postmenopausal women (0.6 mg/kg), over a period of 15 days. The results were compared to those of untreated OVX + 2K1C, OVX, and control rats. The treatment with C. racemosa caused a significant reduction in blood pressure. In the liver, treatment did not prevent the development of steatosis, and it reduced the mitochondrial and peroxisomal capacity to oxidize octanoyl-CoA compared to the untreated animals. In addition, C. racemosa caused numerous undesirable effects on the liver redox status: it increased the mitochondrial reactive oxygen species generation, an event that was not accompanied by an increase in the activity of superoxide dismutase, and it induced a decrease in peroxisomal catalase activity. Although the reduced glutathione content had not been affected, a phenomenon that probably reflected the restoration of glucose-6-phosphate dehydrogenase activity by C. racemosa, oxidative damage was evidenced by the elevated level of thiobarbituric acid-reactive substances found in the liver of treated animals. PMID:22684021

Campos, Lilian Brites; Gilglioni, Eduardo Hideo; Garcia, Rosângela Fernandes; Brito, Márcia do Nascimento; Natali, Maria Raquel Marçal; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2012-08-15

224

Low dose angiotensin II infusions into the renal artery induce chronic hypertension in conscious dogs.  

PubMed

Angiotensin II was infused at 0.5 ng/kg/min either directly into the left renal artery (n = 5) or intravenously (n = 4) for 28 days in conscious dogs. Renal artery infusion of angiotensin II had no significant effect on mean arterial pressure after 1 and 24 h, but pressure had increased by 12 +/- 2, 12 +/- 4, 8 +/- 3 and 13 +/- 3 mmHg on days 7, 14, 21 and 28, respectively, during infusion. Renal blood flow decreased significantly at 24 hours (p = 0.02) but was not significantly reduced subsequently. Over days 7-28, central venous pressure and haematocrit rose significantly but body weight did not change significantly. During intravenous infusion of angiotensin II, arterial pressure increased (5 +/- 4, 7 +/- 5 and 5 +/- 3 mmHg on days 7, 14 and 21, respectively), body weight rose and haematocrit fell significantly, but central venous pressure did not change. Thus, angiotensin II infused into the renal artery, at a dose which had no initial pressor effect, produced chronic, stable hypertension, with equivocal evidence of renal fluid retention. We conclude that elevated levels of angiotensin II in the kidney alone can cause chronic hypertension. PMID:9116928

Fitzgerald, S M; Stevenson, K M; Evans, R G; Anderson, W P

1997-01-01

225

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

226

[Stereomorphometric study of target organs in rats with hereditary stress-induced arterial hypertension at different periods of postnatal ontogenesis under changed conditions of nursing].  

PubMed

In rats with inherited stress-induced arterial hypertension (ISIAH strain), myocardium, adrenal gland, and renal glomerular apparatus were studied at different periods of postnatal ontogenesis (3 weeks and 6 months) to assess the influence of the changed conditions of nursing on the development of a hypertensive status and structural-functional characteristics of target organs. It was demonstrated that nursing of rats by foster normotensive Wistar females exerted a modulating influence upon the realization of stress-determined program of arterial hypertension development, seemingly delaying it and alleviating the negative consequences in respect to the target organs, through increased effectiveness of recruitment of adaptive-compensatory organism reserves, however, on the whole, it did not interrupt this program. PMID:16400930

Shmerling, M D; Buzueva, I I; Korostyshevskaia, I M; Lazarev, V A; Maksimov, V F; Filiushina, E E; Markel', A L; Iakobson, G S

2005-01-01

227

Hypertension - overview  

MedlinePLUS Videos and Cool Tools

If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

228

Role of the median preoptic nucleus in chronic angiotensin II-induced hypertension.  

PubMed

Several lines of evidence implicate the median preoptic nucleus (MnPO) as a downstream site of activation following binding of angiotensin II (ANG II) at the subfornical organ and organum vasculosum of the lamina terminalis. We have shown previously that electrolytic lesion of the MnPO attenuated the increased blood pressure response to chronic intravenous infusion of ANG II. However, whether MnPO neurons or fibers that pass through this region contribute to this response is not clear. In the present study, to distinguish the relative importance of MnPO neurons from fibers of passage in the hypertensive response to chronic ANG II administration, male Sprague Dawley rats were randomly assigned to either sham (iSHAM) or ibotenic acid lesion of the MnPO (iMnPOx). In the iMnPOx group, 200 nl of ibotenic acid in phosphate buffer saline (5 microg/microl) was injected into each of 3 predetermined coordinates targeted at the entire MnPO. After a week of recovery, rats were instrumented with venous catheters, and radiotelemetric transducers for the intravenous administration of ANG II and the measurement of mean arterial pressure (MAP) and heart rate, respectively. Rats were given another week to recover. iSHAM and iMnPOx animals were then infused with saline (7 ml 0.9% NaCl/day) for 3 days as a control period, followed by 10 consecutive days of intravenous ANG II infusion (10 ng kg(-1) min(-1)), and finally a recovery period similar to control. Throughout the protocol, a 0.4% NaCl diet and distilled water were provided ad libitum. By day 8 of ANG II infusion, MAP had increased 54+/-2 mm Hg in iSHAM rats (n=8). The hypertensive response to ANG II was significantly attenuated in the iMnPOx rats (n=9), in which MAP had only increased 29+/-3 mm Hg. These results support the hypothesis that neurons of the MnPO are involved in the central neural pathway mediating the chronic hypertensive effects of ANG II. PMID:18760264

Ployngam, Trasida; Collister, John P

2008-10-31

229

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in dahl salt-sensitive rats.  

PubMed

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

230

Cytochrome P4501A1 Is Required for Vascular Dysfunction and Hypertension Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin  

PubMed Central

National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAHs). Furthermore, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (ROS), endothelial dysfunction, and hypertension. Because TCDD induces cytochrome P4501A1 (CYP1A1) and CYP1A1 can increase ROS, we tested the hypothesis that TCDD-induced endothelial dysfunction and hypertension are mediated by CYP1A1. CYP1A1 wild-type (WT) and knockout (KO) mice were fed one control or TCDD-containing pill (180 ng TCDD/kg, 5 days/week) for 35 days (n = 10–14/genotype/treatment). Blood pressure was monitored by radiotelemetry, and liver TCDD concentration, CYP1A1 induction, ROS, and aortic reactivity were measured at 35 days. TCDD accumulated to similar levels in livers of both genotypes. TCDD induced CYP1A1 in endothelium of aorta and mesentery without detectable expression in the vessel wall. TCDD also induced superoxide anion production, measured by NADPH-dependent lucigenin luminescence, in aorta, heart, and kidney of CYP1A1 WT mice but not KO mice. In contrast, TCDD induced hydrogen peroxide, measured by amplex red assay, to similar levels in aorta of CYP1A1 WT and KO mice but not in heart or kidney. TCDD reduced acetylcholine-dependent vasorelaxation in aortic rings of CYP1A1 WT mice but not in KO mice. Finally, TCDD steadily increased blood pressure after 15 days, which plateaued after 25 days (+20 mmHg) in CYP1A1 WT mice but failed to alter blood pressure in KO mice. These results demonstrate that CYP1A1 is required for TCDD-induced cardiovascular superoxide anion production, endothelial dysfunction, and hypertension. PMID:20634294

Kopf, Phillip G.; Scott, Jason A.; Agbor, Larry N.; Boberg, Jason R.; Elased, Khalid M.; Huwe, Janice K.; Walker, Mary K.

2010-01-01

231

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats  

PubMed Central

Background The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Methods Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. Results The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71?±?0.05 for MCT group to 0.50?±?0.06 for MCT?+?NAC group, p?

2014-01-01

232

Attenuation of hypoosmotic stress-induced ANP secretion via I(Cl,swell) in renal hypertensive rat atria.  

PubMed

Cardiac hypertrophy, an adaptive process to an increased hemodynamic overload, includes not only an increase in cell size but also qualitative changes in constituent proteins. Although swelling-activated chloride channels (I(Cl,swell)) chronically activate in hypertrophied atrial myocytes, the role of I(Cl,swell) in regulation of atrial natriuretic peptide (ANP) release is poorly understood. We investigated the effects of I(Cl,swell) on ANP release and contractility and its modification in hypertrophied rat atria. To stimulate I(Cl,swell), hypoosmotic HEPES buffered solution (0.8T, 0.7T and 0.6T) was perfused into isolated perfused beating atria. The hypoosmotic HEPES buffered solution increased ANP release as compared to isoosmotic buffered solution (1T) in an osmolarity-reduction dependent manner. Atrial contractility and extracellular fluid translocation did not change. Exposure to hypoosmotic buffer (0.8T) containing low chloride (8mM), tamoxifen or diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) significantly attenuated hypoosmolarity-induced ANP release. The pretreatment with genistein, okdaic acid, U73122, GF109203x, and staurosporine attenuated hypoosmolarity-induced ANP release whereas orthovanadate augmented it significantly. In hypertrophied atria from renal hypertensive rats, hypoosmolarity-induced ANP release was markedly attenuated and DIDS-induced decrease in ANP release and negative inotropy were augmented as compared to sham-operated rat atria. Therefore, we suggest that I(Cl,swell) may partly participate hypoosmolarity-induced ANP release through protein tyrosine kinase and phospholipase C-protein kinase C pathway. The modification of responses of ANP release to hypoosmolarity and DIDS in hypertrophied atria may relate to changes in I(Cl,swell) activity by persistent high blood pressure. PMID:18582990

Bai, Guang Yi; Yuan, Kuichang; Park, Woo Hyun; Kim, Sung Zoo; Kim, Suhn Hee

2008-09-01

233

Microbead-Induced Ocular Hypertensive Mouse Model for Screening and Testing of Aqueous Production Suppressants for Glaucoma  

PubMed Central

Purpose. To characterize the microbead-induced ocular hypertension (OHT) mouse model and investigate its potential use for preclinical screening and evaluation of ocular hypotensive agents, we tested the model's responses to major antiglaucoma drugs. Methods. Adult C57BL/6J mice were induced to develop OHT unilaterally by intracameral injection of microbeads. The effects of the most commonly used ocular hypotensive drugs, including timolol, brimonidine, brinzolamide, pilocarpine, and latanoprost, on IOP and glaucomatous neural damage were evaluated. Degeneration of retinal ganglion cells (RGCs) and optic nerve axons were quantitatively assessed using immunofluorescence labeling and histochemistry. Thickness of the ganglion cell complex (GCC) was also assessed with spectral-domain optical coherence tomography (SD-OCT). Results. A microbead-induced OHT model promptly responded to drugs, such as timolol, brimonidine, and brinzolamide, that lower IOP through suppressing aqueous humor production and showed improved RGC and axon survival as compared to vehicle controls. Accordingly, SD-OCT detected significantly less reduction of GCC thickness in mice treated with all three aqueous production suppressants as compared to the vehicle contol–treated group. In contrast, drugs that increase aqueous outflow, such as pilocarpine and latanoprost, failed to decrease IOP in the microbead-induced OHT mice. Conclusions. Microbead-induced OHT mice carry dysfunctional aqueous outflow facility and therefore offer a unique model that allows selective screening of aqueous production suppressant antiglaucoma drugs or for studying the mechanisms regulating aqueous humor production. Our data set the stage for using GCC thickness assessed by SD-OCT as an imaging biomarker for noninvasive tracking of neuronal benefits of glaucoma therapy in this model. PMID:22599582

Yang, Qiang; Cho, Kin-Sang; Chen, Huihui; Yu, Dekuang; Wang, Wan-Heng; Luo, Gang; Pang, Iok-Hou; Guo, Wenyi; Chen, Dong Feng

2012-01-01

234

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

235

Chronic unilateral occlusion of an extrapulmonary primary bronchus induces pulmonary hypertension syndrome (ascites) in male and female broilers.  

PubMed

Previously, it was demonstrated that acute (4 min) and chronic (12 d) occlusion of an extrapulmonary primary bronchus triggers pulmonary hypertension but not pulmonary hypertension syndrome (PHS, ascites) in broilers. The present study was conducted to determine whether a more prolonged period of bronchus occlusion causes PHS similar to that induced by clamping one pulmonary artery. Male and female broiler chicks, 14 to 18 d old, were anesthetized, the thoracic inlet was opened, and a silver clip was positioned to fully obstruct the left extrapulmonary primary bronchus (BRONCHUS CLAMP group) or the left pulmonary artery (PA-CLAMP group). Sham-operated chicks were anesthetized and the thoracic inlet was opened; however, neither the pulmonary artery nor the bronchus was clamped (SHAM group). An electrocardiogram (ECG) was obtained whenever clinical ascites became apparent in individual broilers, or prior to the final necropsy for broilers surviving to the end (Day 36) of the experiment. The right:total ventricular weight ratio (RV:TV) was evaluated as an index of pulmonary arterial pressure. Early post-surgical mortality (up to 21 d of age) was higher in the PA-CLAMP group (27% for males and females combined) than in the BRONCHUS CLAMP (10%) and SHAM (2%) groups. Cumulative ascites mortality (Days 22 to 36) also was higher in the PA-CLAMP group (86% for males, 77% for females) than in the BRONCHUS CLAMP (69% for males, 41% for females) and SHAM (23% for males, 0% for females) groups. Ascitic birds in all treatment groups had higher RV:TV ratios and more negative ECG Lead II S-wave amplitudes than nonascitic birds, reflecting the right ventricular hypertrophy and generalized ventricular dilation typically associated with PHS. These results demonstrate that unilateral bronchus occlusion is an effective experimental model for triggering ascites at a lower incidence than that obtained by occluding one pulmonary artery. Following the onset of pulmonary hypertension, the pathophysiological progression leading to ascites appears to be similar for broilers with either unilateral bronchus or pulmonary artery occlusion. PMID:9057225

Wideman, R F; Kirby, Y K; Owen, R L; French, H

1997-02-01

236

Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia–reperfusion damage in the rat  

PubMed Central

Background and purpose: Phosphodiesterase-5 inhibitors are beneficial in pulmonary hypertension and congestive heart failure, the two conditions associated with coronary heart disease and ischaemia. We investigated whether sildenafil counteracts the cardiovascular alterations induced by N ?-nitro-L-arginine methyl ester (L-NAME) in the rat. Experimental approach: Sildenafil was given orally to rats at doses of 0.37, 0.75 or 1.5?mg kg?1day?1 for four weeks, either alone or with L-NAME (35-40?mg kg?1 day?1 in the drinking water). Systolic blood pressure and urinary parameters (6-keto-prostaglandin F1?, thromboxane B2, 8-isoprostane-prostaglandin F2? and nitrite/nitrate) were measured in conscious rats. Isolated hearts were subjected to low flow ischaemia–reperfusion, and myocardial levels of guanosine 3', 5'cyclic monophosphate (cGMP) were determined. Endothelial vascular dysfunction was examined in aortic rings. Key results: Sildenafil dose-dependently prevented the rise in systolic blood pressure in L-NAME-treated rats. This activity was associated with a normalization of urinary 8-isoprostane-prostaglandin F2? and other biochemical parameters. In perfused hearts, the post-ischaemic ventricular dysfunction was worse in preparations from L-NAME-treated rats than in controls. Sildenafil dose-dependently reduced this effect, and creatine kinase and lactate dehydrogenase release were lower too. cGMP levels, which were low in myocardial tissue from L-NAME-treated rats, were restored by sildenafil. In noradrenaline-precontracted aortic rings from L-NAME-treated rats acetylcholine lost its vasorelaxant effect, and sildenafil restored it. Conclusion and implications: In a rat model of chronic nitric oxide deprivation, where hypertension and aggravation of post-ischaemic ventricular dysfunction are associated with loss of vascular endothelium-relaxant function, sildenafil provided significant cardiovascular protection, primarily by maintaining tissue cGMP levels. PMID:17245365

Rossoni, G; Manfredi, B; De Gennaro Colonna, V; Berti, M; Guazzi, M; Berti, F

2007-01-01

237

Smooth Muscle Specific Rac1 Deficiency Induces Hypertension by Preventing p116RIP3?Dependent RhoA Inhibition  

PubMed Central

Background Increasing evidence implicates overactivation of RhoA as a critical component of the pathogenesis of hypertension. Although a substantial body of work has established that Rac1 functions antagonize RhoA in a broad range of physiological processes, the role of Rac1 in the regulation of vascular tone and blood pressure is not fully elucidated. Methods and Results To define the role of Rac1 in vivo in vascular smooth muscle cells (vSMC), we generated smooth muscle (SM)?specific Rac1 knockout mice (SM?Rac1?KO) and performed radiotelemetric blood pressure recordings, contraction measurements in arterial rings, vSMC cultures and biochemical analyses. SM?Rac1?KO mice develop high systolic blood pressure sensitive to Rho kinase inhibition by fasudil. Arteries from SM?Rac1?KO mice are characterized by a defective NO?dependent vasodilation and an overactivation of RhoA/Rho kinase signaling. We provide evidence that Rac1 deletion?induced hypertension is due to an alteration of cGMP signaling resulting from the loss of Rac1?mediated control of type 5 PDE activity. Consequently, cGMP?dependent phosphorylation and binding of RhoA with its inhibitory partner, the phosphatase?RhoA interacting protein (p116RIP3), are decreased. Conclusions Our data reveal that the depletion of Rac1 in SMC decreases cGMP?dependent p116RIP3/RhoA interaction and the subsequent inhibition of RhoA signaling. Thus, we unveil an in vivo role of Rac1 in arterial blood pressure regulation and a new pathway involving p116RIP3 that contributes to the antagonistic relationship between Rac1 and RhoA in vascular smooth muscle cells and their opposite roles in arterial tone and blood pressure. PMID:24938713

André, Gwennan; Sandoval, Juan E.; Retailleau, Kevin; Loufrani, Laurent; Toumaniantz, Gilles; Offermanns, Stefan; Rolli?Derkinderen, Malvyne; Loirand, Gervaise; Sauzeau, Vincent

2014-01-01

238

Extravasation of blood-borne immunoglobulin G through blood-brain barrier during adrenaline-induced transient hypertension in the rat.  

PubMed

The effect of transient hypertension on blood-brain barrier (BBB) permeability, particularly on extravasation of immunoglobulin G (IgG), has not been fully understood. In the present experiment, we investigated the time course of endogenous albumin and IgG extravasation through BBB and the localization of extravasated IgG in brain parenchyma during adrenaline(AD)-induced transient hypertension in the rat by using Evans blue fluorescence, immunohistochemistry, and Western blot. The results showed that a bolus injection of AD (10 microg/kg) induced a transient elevation of arterial pressure lasting about 1 min. The endogenous albumin and IgG entered the brain parenchyma via BBB only when hypertension occurred. Electron microscopically, the IgG-like immunoreactivities were predominantly seen in the cytoplasm of endothelia of capillaries, pericytes, extracellular space of parenchyma, and the cytoplasm of glial cells. The results suggest that circulating IgG or antibodies might contact the structures of brain parenchyma through passage of BBB when its permeability is temporally changed by transient hypertension. This phenomenon implies a possible mechanism of pathogenesis for immune-mediated diseases in the brain. PMID:15204054

Kuang, Fang; Wang, Bai-Ren; Zhang, Ping; Fei, Ling-Ling; Jia, Yi; Duan, Xiao-Li; Wang, Xi; Xu, Zhen; Li, Gai-Li; Jiao, Xi-Ying; Ju, Gong

2004-06-01

239

Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats.  

PubMed

Hypertension is closely associated with vascular endothelial dysfunction. The aim of this study was to investigate the effects of Angiotensin II (ANG II) receptor antagonist losartan on the blood-brain barrier (BBB) permeability in L-NAME-induced hypertension and/or in ANG II-induced acute hypertension in normotensive and hypertensive rats. Systolic blood pressure was measured by tail cuff method before, during and following L-NAME treatment (1 g/L). Losartan (3 mg/kg) was given to the animal for five days. Acute hypertension was induced by ANG II (60 microg/kg). Arterial blood pressure was directly measured on the day of the experiment. BBB disruption was quantified according to the extravasation of the albumin-bound Evans blue dye. Losartan significantly reduced the mean arterial blood pressure from 169 +/- 3.9 mmHg to 82 +/- 2.9 mmHg in L-NAME and from 171 +/- 2.9 mmHg to 84 +/- 2.9 in L-NAME plus losartan plus ANG II groups (p < 0.05). The content of Evans blue dye in the cerebral cortex significantly increased in L-NAME (p < 0.01). Moreover, the content of Evans blue dye markedly increased in the cerebellum (p < 0.001) and slightly increased in diencephalon region (p < 0.05) in L-NAME plus ANG II. Losartan reduced the increased BBB permeability to Evans blue dye in L-NAME (p < 0.01) and L-NAME plus ANG II (p < 0.001). These results indicate that L-NAME and L-NAME plus ANG II both lead to an increase in microvascular Evans blue dye efflux to brain, and losartan treatment attenuates this protein-bound dye transport into brain tissue presumably due to its protective effect on endothelial cells of brain vessels. PMID:12084390

Kucuk, Mutlu; Kaya, Mehmet; Kalayci, Rivaze; Cimen, Vedat; Kudat, Hasan; Arican, Nadir; Elmas, Imdat; Korkut, Ferruh

2002-07-12

240

Plasma taurine levels in broilers with pulmonary hypertension syndrome induced by unilateral pulmonary artery occlusion.  

PubMed

Low plasma levels of taurine are associated with losses of cardiac sarcomeric proteins, leading to heart failure in mammals. Recently, it was proposed that cardiac taurine depletion serves to defend the heart against injury caused by regional ischemia in mammals. The role of taurine has not been well documented in broilers, particularly in relation to pulmonary hypertension syndrome (PHS; ascites). Three independent experiments evaluated plasma taurine in male broilers by utilizing the following treatments: unoperated controls (CONTROL; n = 10 in each experiment); sham operated (SHAM; n = 11, 12, and 10); or, unilaterally pulmonary artery clamped (PAC; n = 18, 29, and 24) that did (PAC-ascites) or did not (PAC-normal) develop ascites within 12 d postsurgery. Plasma samples were collected 9 and 11 d postsurgery in Experiments 1 and 2, respectively, and 2 d before and 4, 8, and 12 d after surgery in Experiment 3. Plasma taurine was analyzed by HPLC. Twelve days postsurgery, the birds were euthanatized, and ventricles were weighed for calculating the right:total ventricular weight ratio (RV:TV). The RV:TV of PAC birds (>0.35) consistently was higher (P < 0.01) than that of CONTROL and SHAM birds (<0.27 and 0.25, respectively). In Experiments 1 and 2, plasma taurine was higher (P < 0.05) in PAC-ascites (380 and 370 nmol/mL) than in SHAM broilers (183 and 186 nmol/mL), whereas CONTROL (262 and 278 nmol/mL) and PAC-normal (362 and 300 nmol/mL) broilers tended to have intermediate plasma taurine levels. In Experiment 3, PAC birds had higher (P < 0.05) plasma taurine at 8 and 12 d postsurgery when compared with presurgery levels, whereas plasma taurine was unchanged over time in CONTROL and SHAM birds. These results suggest cardiac taurine may be released into the plasma as a protective mechanism in response to the induction of pulmonary hypertension, hypoxemia, and right-side heart failure, similar to the mechanism reported for protecting cardiac muscle from ischemia in mammals. PMID:10560839

Ruiz-Feria, C A; Beers, K W; Kidd, M T; Wideman, R F

1999-11-01

241

Resolution of whipple disease-induced pulmonary hypertension following antibiotic therapy.  

PubMed

Whipple disease is a disorder caused by Tropheryma whipplei, a ubiquitous Gram-positive bacillus. In addition to gastrointestinal manifestations, many other systems may be involved in Whipple disease. Pulmonary hypertension (PH) is a rare manifestation of Whipple disease, and its clinical course is not well established. We report a case of a 45-year-old woman who presented with typical gastrointestinal manifestations of Whipple disease, which was diagnosed by duodenal biopsy. She was also noted to have elevated pulmonary arterial pressures on transthoracic echocardiography. There was no evidence of left-sided valvular disease, hypertrophy, or dyskinesis, and there was no evidence of endocarditis. The patient was started on intravenous ceftriaxone for 6 weeks and then transitioned to oral trimethoprim-sulfamethoxazole for a year. The patient demonstrated clinical improvement, endoscopic and histologic improvement, and also resolution of PH. This is the third reported case of PH that is convincingly secondary to Whipple disease that resolved after appropriate antibiotic therapy. PMID:23344104

Hoskote, Sumedh S; Georgescu, Anca; Ganjhu, Lisa; Zeizafoun, Nebras; Polsky, Bruce

2014-01-01

242

Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level.  

PubMed

We determined whether postnatal pulmonary hypertension induced by 70% of pregnancy at high altitude (HA) persists once the offspring return to sea level and investigated pulmonary vascular mechanisms operating under these circumstances. Pregnant ewes were divided into two groups: conception, pregnancy, and delivery at low altitude (580 m, LLL) and conception at low altitude, pregnancy at HA (3,600 m) from 30% of gestation until delivery, and return to lowland (LHL). Pulmonary arterial pressure (PAP) was measured in vivo. Vascular reactivity and morphometry were assessed in small pulmonary arteries (SPA). Protein expression of vascular mediators was determined. LHL lambs had higher basal PAP and a greater increment in PAP after N(G)-nitro-L-arginine methyl ester (20.9 ± 1.1 vs. 13.7 ± 0.5 mmHg; 39.9 ± 5.0 vs. 18.3 ± 1.3 mmHg, respectively). SPA from LHL had a greater maximal contraction to K(+) (1.34 ± 0.05 vs. 1.16 ± 0.05 N/m), higher sensitivity to endothelin-1 and nitroprusside, and persistence of dilatation following blockade of soluble guanylate cyclase. The heart ratio of the right ventricle-to-left ventricle plus septum was higher in the LHL relative to LLL. The muscle area of SPA (29.3 ± 2.9 vs. 21.1 ± 1.7%) and the protein expression of endothelial nitric oxide synthase (1.7 ± 0.1 vs. 1.1 ± 0.2), phosphodiesterase (1.4 ± 0.1 vs. 0.7 ± 0.1), and Ca(2+)-activated K(+) channel (0.76 ± 0.16 vs. 0.30 ± 0.01) were greater in LHL compared with LLL lambs. In contrast, LHL had decreased heme oxygenase-1 expression (0.82 ± 0.26 vs. 2.22 ± 0.44) and carbon monoxide production (all P < 0.05). Postnatal pulmonary hypertension induced by 70% of pregnancy at HA promotes cardiopulmonary remodeling that persists at sea level. PMID:20881096

Herrera, Emilio A; Riquelme, Raquel A; Ebensperger, Germán; Reyes, Roberto V; Ulloa, César E; Cabello, Gertrudis; Krause, Bernardo J; Parer, Julian T; Giussani, Dino A; Llanos, Aníbal J

2010-12-01

243

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; Oliván-Viguera, Aida; Lloyd, Eric E.; Bryan, Robert M.; Simonsen, Ulf; Köhler, Ralf

2013-01-01

244

Contractions induced by potassium-free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats.  

PubMed Central

1. Vascular contractions induced by K(+)-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2. In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 microM) inhibited the contractions more effectively in SHR than WKY. 3. Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K(+)-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4. The presence of intact vascular endothelium attenuated the K(+)-free contractions in both strains, the attenuation being smaller in SHR than WKY. NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 microM), but not indomethacin (10 microM), abolished the attenuating effect of endothelium on the K(+)-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5. The re-addition of K+ after full K(+)-free contractions dose-dependently relaxed the rings. The rate of this K(+)-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 5 PMID:1504724

Arvola, P.; Pörsti, I.; Vuorinen, P.; Pekki, A.; Vapaatalo, H.

1992-01-01

245

Sequencing of the 5? region of the Lngfr gene associated with stress-induced arterial hypertension in ISIAH rats  

Microsoft Academic Search

163 Inbred animal strains are broadly used in molecular studies of essential arterial hypertension (HTN). Different strains can be regarded as models of different HTN forms, whose development involves various systems and mechanisms of arterial blood pressure regulation. A strain of rats with inherited stressinduced arterial hypertension (ISIAH strain) has been developed at the Institute of Cytology and Genetics for

L. A. Fedoseeva; G. M. Dymshits; A. L. Markel

2008-01-01

246

Therapeutic Efficacy of AAV1.SERCA2a in Monocrotaline-Induced Pulmonary Arterial Hypertension  

PubMed Central

Background Pulmonary arterial hypertension (PAH) is characterized by dysregulated proliferation of pulmonary artery smooth muscle cells leading to (mal)adaptive vascular remodeling. In the systemic circulation, vascular injury is associated with downregulation of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and alterations in Ca2+ homeostasis in vascular smooth muscle cells that stimulate proliferation. We, therefore, hypothesized that downregulation of SERCA2a is permissive for pulmonary vascular remodeling and the development of PAH. Methods and Results SERCA2a expression was decreased significantly in remodeled pulmonary arteries from patients with PAH and the rat monocrotaline model of PAH in comparison with controls. In human pulmonary artery smooth muscle cells in vitro, SERCA2a overexpression by gene transfer decreased proliferation and migration significantly by inhibiting NFAT/STAT3. Overexpresion of SERCA2a in human pulmonary artery endothelial cells in vitro increased endothelial nitric oxide synthase expression and activation. In monocrotaline rats with established PAH, gene transfer of SERCA2a via intratracheal delivery of aerosolized adeno-associated virus serotype 1 (AAV1) carrying the human SERCA2a gene (AAV1.SERCA2a) decreased pulmonary artery pressure, vascular remodeling, right ventricular hypertrophy, and fibrosis in comparison with monocrotaline-PAH rats treated with a control AAV1 carrying ?-galactosidase or saline. In a prevention protocol, aerosolized AAV1.SERCA2a delivered at the time of monocrotaline administration limited adverse hemodynamic profiles and indices of pulmonary and cardiac remodeling in comparison with rats administered AAV1 carrying ?-galactosidase or saline. Conclusions Downregulation of SERCA2a plays a critical role in modulating the vascular and right ventricular pathophenotype associated with PAH. Selective pulmonary SERCA2a gene transfer may offer benefit as a therapeutic intervention in PAH. PMID:23804254

Hadri, Lahouaria; Kratlian, Razmig G.; Benard, Ludovic; Maron, Bradley A.; Dorfmüller, Peter; Ladage, Dennis; Guignabert, Christophe; Ishikawa, Kiyotake; Aguero, Jaume; Ibanez, Borja; Turnbull, Irene C.; Kohlbrenner, Erik; Liang, Lifan; Zsebo, Krisztina; Humbert, Marc; Hulot, Jean-Sébastien; Kawase, Yoshiaki; Hajjar, Roger J.; Leopold, Jane A.

2014-01-01

247

Fasudil reversed MCT-induced and chronic hypoxia-induced pulmonary hypertension by attenuating oxidative stress and inhibiting the expression of Trx1 and HIF-1?.  

PubMed

Antioxidant therapy attenuates pulmonary hypertension (PH). In the present study, we tested the antioxidant effects of fasudil against PH in rats. Monocrotaline (MCT)-induced and chronic hypoxia-induced PH models of rats were established, and the haemodynamic and pathomorphologic results of three different doses of fasudil (10 mg/kg, 30 mg/kg, and 75 mg/kg per day) were subsequently compared with those of bosentan (30 mg/kg per day). Additionally, the protein expressions of thioredoxin-1 (Trx1) and hypoxia inducible factor-1? (HIF-1?), the content of superoxide dismutase (SOD), and the levels of hydrogen peroxide (H2O2), malonyldialdehyde (MDA), and hydroxy radical (·OH) were investigated. Fasudil effectively reduced the right ventricular systolic pressure (RVSP) and alleviated right ventricle (RV) hypertrophy, as well as the histological changes in the pulmonary arterioles. Moreover, fasudil markedly lessened the expression of Trx1 and HIF-1?, up-regulated the concentration of SOD, and lowered the levels of H2O2, MDA, and ·OH. In conclusion, fasudil is a notably attractive potential therapy for PH. PMID:24973470

Liu, Manling; Wang, Yanxia; Zheng, Lianhe; Zheng, Wansong; Dong, Kai; Chen, Shuai; Zhang, Bo; Li, Zhichao

2014-09-15

248

Functional role of Cl ? channels in acidic pH-induced contraction of the aorta of spontaneously hypertensive and Wistar Kyoto rats  

Microsoft Academic Search

pH regulates various cellular functions. Previously, we have described that acidic pH produces depolarization and contraction in isolated aorta from spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats [Br. J. Pharmacol. 118 (1996) 485]. The aim of the present study was to investigate the involvement of Cl? channels in acidic pH-induced contraction. Changing the pH of the bathing solution from

Dileep Kumar Rohra; Shin-ya Saito; Yasushi Ohizumi

2002-01-01

249

Effect of Yucca schidigera extract on blood pressure, antioxidant activity and some blood parameters in the L-name-induced hypertensive rats  

Microsoft Academic Search

Summary: The present study was aimed at investigating the effects of dietary supplementation of Yucca schidigera extract (YSE) on blood pressure, antioxidant activity and some biochemical parameters in the L-NAME-induced hypertensive rats. The study was performed on eighteen male Sprague-Dawley rats divided into 3 groups with 6 animals per group: 1) Control, fed standard chow ad libitum, 2) N-nitro-L-arginine methyl

Aziz BÜLBÜL; Abdullah ERYAVUZ; Gülcan AVCI; ?smail KÜÇÜKKURT; A. Fatih

250

Effects of acupuncture on nNOS and iNOS expression in the rostral ventrolateral medulla of stress-induced hypertensive rats.  

PubMed

This study was to observe the changes of the neuronal and inducible nitric oxide synthase (nNOS & iNOS) as well as their mRNAs in the rostral ventrolateral medulla (RVLM) of stress-induced hypertensive rats before and after acupuncture, and thereby to infer the curative mechanism of acupuncture on hypertension. The result indicated that the systolic blood pressure (SBP) of stress group rats was increased significantly (P < 0.01), it was accompanied that the expression of nNOS in the RVLM, including the immunoreactive neuron number (P < 0.05), the optical density (OD) (P < 0.01), and the mRNA (P < 0.01) were obviously elevated, while those of iNOS (P < 0.05, P < 0.01 and P < 0.01) were evidently lowered in the stress-induced hypertensive rats. Electroacupuncture (EA) points at "Zusanli" (St. 36) and "Lanwei" (Extra 37) on the same hindlimb were stimulated by an EA apparatus (Type G6805-2) with dense sparse wave (4-20Hz) and 4mA intensity. EA application could return the SBP (P < 0.05), and the changes on the expression of both nNOS and iNOS (P < 0.05, P < 0.01 and P < 0.01). These results suggest that the curative mechanism of acupuncture on stress-induced hypertension is related to the changes of nNOS and iNOS in the RVLM of rats. PMID:16617691

Huang, Yu-Ling; Fan, Ming-Xin; Wang, Jin; Li, Li; Lu, Ning; Cao, Yin-Xiang; Shen, Lin-Lin; Zhu, Da-Nian

2005-01-01

251

Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic Wistar rats.  

PubMed

Acute subcutaneous administration of Angiotensin II (Ang II) causes a rise in blood pressure in diabetic Wistar rats. Diabetes was induced using streptozotocin (70 mg/kg, i.v.). Chronic administration of pomegranate juice (PJ) extract (100 mg/kg and 300 mg/kg; p.o. for 4 weeks) obtained from Punica granatum (punicaceae) fruits reduced the mean arterial blood pressure and vascular reactivity changes to various catecholamines and also reversed the biochemical changes induced by diabetes and Ang II. PJ treatment also caused a significant decrease in levels of thiobarbituric acid reactive substances (TBARS) in kidney and pancreas while activities of enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) showed significant elevation. The cumulative concentration response curve (CCRC) of Ang II was shifted towards right in rats treated with PJ using isolated strip of ascending colon. In histopathological examination, PJ treatment prevented the tubular degenerative changes induced by diabetes. The results suggest that the PJ extract could prevent the development of high blood pressure induced by Ang II in diabetic rats probably by combating the oxidative stress induced by diabetes and Ang II and by inhibiting ACE activity. In conclusion, PJ has antihypertensive action in Ang II diabetic model. PMID:20020514

Mohan, Mahalaxmi; Waghulde, Harshal; Kasture, Sanjay

2010-06-01

252

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...

253

High Sodium Intake Decreases Pressure-Induced (Myogenic) Tone and Flow-Induced Dilation in Resistance Arteries From Hypertensive Rats  

Microsoft Academic Search

High sodium intake has been associated with a higher blood pressure level. Resistance arteries are the main determinants of blood pressure. They are largely regulated by pressure (tensile stress)-induced tone (myogenic tone, MT) and by flow (shear stress)-induced dilation (FD). Thus, we studied the effect of NaCl (8%) intake for 8 weeks on FD and MT in mesenteric resistance arteries

Khalid Matrougui; Pierre Schiavi; David Guez; Daniel Henrion

254

Benefit of combined therapy with nicorandil and colchicine in preventing monocrotaline-induced rat pulmonary arterial hypertension.  

PubMed

This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p<0.001). Pulmonary damage severity (thickened alveolar septum and pulmonary arteriolar wall, decreased alveolar-sac numbers), number of CD3+ cells, and protein expressions of inflammatory (MMP-9, NF-?B, VCAM-1, angiotensin II-receptor), apoptotic (Bax, caspase 3, cleaved PARP), and fibrotic (TGF-?, Smad3) biomarkers showed an identical pattern compared to that of RVSBP, whereas pulmonary expressions of anti-apoptotic (Bcl-2) and anti-fibrotic (BMP-2, Smad1/5) biomarkers displayed a reverse pattern (all p<0.01). The protein expressions of RV damage markers (BNP, caspase 3) were increased, whereas expression of biomarker for RV functional preservation (Cx43) was reduced in group 2 compared with group 1, elevated in groups 3 and 4 compared to group 2, and further increased in group 5 (all p<0.01). Combined therapy with nicorandil and colchicine is superior to either alone in attenuating MCT-induced PAH in rats. PMID:23954457

Lee, Fan-Yen; Lu, Hung-I; Zhen, Yen-Yi; Leu, Steve; Chen, Yung-Lung; Tsai, Tzu-Hsien; Chung, Sheng-Ying; Chua, Sarah; Sheu, Jiunn-Jye; Hsu, Shu-Yuan; Chang, Hsueh-Wen; Sun, Cheuk-Kwan; Yip, Hon-Kan

2013-11-20

255

Fos expression by glutamatergic neurons of the solitary tract nucleus after phenylephrine-induced hypertension in rats.  

PubMed

The baroreflex pathway might include a glutamatergic connection between the nucleus of the solitary tract (NTS) and a segment of the ventrolateral medulla (VLM) called the caudal ventrolateral medulla. The main goal of this study was to seek direct evidence for such a connection. Awake rats were subjected to phenylephrine- (PE-) induced hypertension (N=5) or received saline (N=5). Neuronal activation was gauged by the presence of Fos-immunoreactive (Fos-ir) nuclei. Fos-ir neurons that contained vesicular glutamate transporter 2 mRNA (glutamatergic neurons) or glutamic acid decarboxylase mRNA (GABAergic neurons) were mapped throughout the medulla oblongata. Saline-treated rats had very few Fos-ir neurons. In PE-treated rats, Fos-ir neurons were detected in both NTS and VLM. In NTS, 72% of Fos-ir neurons were glutamatergic and 26% were GABAergic. In the VLM, 41% of Fos-ir neurons were glutamatergic and 56% were GABAergic. In VLM, Fos-ir glutamatergic neurons were evenly distributed and were often catecholaminergic, whereas Fos-ir GABAergic cells were clustered around Bregma -13.0 mm. This region of the VLM was injected with Fluoro-Gold (FG) in eight rats, four of which received PE and the rest saline. Fos-ir NTS neurons retrogradely labeled with FG were detected only in PE-treated rats. These cells were exclusively glutamatergic and were concentrated within the NTS subnuclei that receive the densest inputs from arterial baroreceptors. In conclusion, PE, presumably via baroreceptor stimulation, induces Fos in glutamatergic and GABAergic neurons in both NTS and VLM. At least 29% of the Fos-ir glutamatergic neurons of NTS project to the vicinity of the VLM GABAergic interneurons that are presumed to mediate the sympathetic baroreflex. PMID:12717712

Weston, Matthew; Wang, Hong; Stornetta, Ruth L; Sevigny, Charles P; Guyenet, Patrice G

2003-06-01

256

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

257

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

PubMed

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; Rabinovitch, Marlene

2014-02-10

258

Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats.  

PubMed

The present study was aimed to evaluate the antihypertensive effect of diosmin in deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA (25 mg/kg body weight) and 1% NaCl in the drinking water for six consecutive weeks. The important pathological events that occurred in DOCA-salt treated rats were significant increase in systolic, diastolic blood pressure, sodium and chloride in serum and lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes) in plasma and tissues (liver, kidney, heart and aorta) and significant decrease in serum potassium, total nitrite and nitrate levels in plasma. The activities of hepatic aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and the levels of renal urea, uric acid, creatinine in serum, water intake, and organ weight (kidney and heart) were significantly increased in DOCA-salt hypertensive rats. DOCA-salt treated rats also showed a significant decrease in body weight, activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocyte and tissues and the levels of reduced glutathione, vitamin C and vitamin E in plasma and tissues. Treatment with diosmin (25, 50 and 100 mg/kg body weight) brings back all the above parameters to near normal level, in which 50 mg/kg body weight showed the highest effect than that of other two doses. Histopathology of heart and kidney also confirmed the protective effect of diosmin. Thus the experiment clearly showed that diosmin acts as an antihypertensive agent against DOCA-salt induced hypertension. PMID:22266490

Silambarasan, Thangarasu; Raja, Boobalan

2012-03-15

259

PARP-Inhibitor Treatment Prevents Hypertension Induced Cardiac Remodeling by Favorable Modulation of Heat Shock Proteins, Akt-1/GSK-3? and Several PKC Isoforms  

PubMed Central

Spontaneously hypertensive rat (SHR) is a suitable model for studies of the complications of hypertension. It is known that activation of poly(ADP-ribose) polymerase enzyme (PARP) plays an important role in the development of postinfarction as well as long-term hypertension induced heart failure. In this study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity and blood pressure were determined at the end of the study. We detected the extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the phosphorylation state of Akt-1Ser473, glycogen synthase kinase (GSK)-3?Ser9, forkhead transcription factor (FKHR)Ser256, mitogen activated protein kinases (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left ventricular function and BNP activity did not differ among the three groups. L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2Thr183-Tyr185, Akt-1Ser473, GSK-3?Ser9, FKHRSer256, and PKC ?Ser729 and the level of Hsp90 were increased, while the activity of PKC ?/?IIThr638/641, ?/?410/403 were mitigated by L-2286 administration. We could detect signs of LV hypertrophy without congestive heart failure in SHR groups. This alteration was prevented by PARP inhibition. Our results suggest that PARP-inhibitor treatment has protective effect already in the early stage of hypertensive myocardial remodeling. PMID:25014216

Deres, Laszlo; Bartha, Eva; Palfi, Anita; Eros, Krisztian; Riba, Adam; Lantos, Janos; Kalai, Tamas; Hideg, Kalman; Sumegi, Balazs; Gallyas, Ferenc; Toth, Kalman; Halmosi, Robert

2014-01-01

260

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

SciTech Connect

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 4 weeks. 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. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced hypertension and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced imbalance of PVN neurotransmitters. • PVN inhibition of ACE attenuates ANG II-induced imbalance of cytokines in the PVN. • PVN blockade of AT1-R attenuates ANG II-induced imbalance of cytokines in the PVN.

Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People's Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

2014-02-01

261

Portal Hypertension  

PubMed Central

Portal hypertension is an increase in pressure in the portal vein and its tributaries. It is defined as a portal pressure gradient (the difference in pressure between the portal vein and the hepatic veins) greater than 5 mm Hg. Although this gradient defines portal hypertension, a gradient of 10 mm Hg or greater defines clinically significant portal hypertension, because this pressure gradient predicts the development of varices,1 decompensation of cirrhosis,2,3 and hepatocellular carcinoma.4 The most direct consequence of portal hypertension is the development of gastroesophageal varices that may rupture and lead to the development of variceal hemorrhage. This article reviews the pathophysiologic bases of the different pharmacologic treatments for portal hypertension in patients with cirrhosis and places them in the context of the natural history of varices and variceal hemorrhage. PMID:20951924

Miñano, Cecilia; Garcia-Tsao, Guadalupe

2010-01-01

262

Effect of hypertension on the structural and functional integrity of the young and aged brain in an inducible transgenic model   

E-print Network

Hypertension has been associated with causing deleterious effects to the cerebrovasculature, which are thought to underlie the formation of white matter lesions (WML) and predispose individuals to age related cognitive ...

Pannozzo, Mercede Alcina

2014-06-28

263

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

PubMed Central

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

2014-01-01

264

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

265

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

266

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

267

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

268

The Anti-hypertensive Drug Prazosin Induces Apoptosis in the Medullary Thyroid Carcinoma Cell Line TT  

PubMed Central

Background/Aim Medullary thyroid carcinoma (MTC) is a tumor associated with poor prognosis since it exhibits high resistance against conventional cancer therapy. Recent studies have shown that quinazolines exhibit a pro-apoptotic effect on malignant cells. The aim of the present study was to elucidate whether MTC cells are affected by quinazolines, in particular prazosin. Materials and Methods Proliferation, apoptosis and cell morphology of the MTC cell line TT were analyzed by WST-1 assay, caspase 3/7 activation tests and microscopy. Fibroblasts were used as control for non-malignant cells. Results Prazosin potently inhibited the growth of TT cells, induced apoptosis and caused vacuolization, as well as needle-like filopodia. Fibroblasts were affected by prazosin in the same way as MTC cells. Conclusion MTC cells are responsive to prazosin treatment similar to other malignancies. The fact that fibroblasts also respond to prazosin further highlights the importance to identify the unknown pro-apoptotic target of quinazolines. PMID:25550532

STRACKE, ANIKA; MEIER-ALLARD, NATHALIE; ABSENGER, MARKUS; INGOLIC, ELISABETH; HAAS, HELGA SUSANNE; PFRAGNER, ROSWITHA; SADJAK, ANTON

2015-01-01

269

Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression  

PubMed Central

Elevated blood pressure (BP) and chronic kidney disease (CKD) are complex traits representing major global health problems1,2. Multiple genome-wide association studies (GWAS) identified common variants giving independent susceptibility for CKD and hypertension in the promoter of the UMOD gene3-9, encoding uromodulin, the major protein secreted in the normal urine. Despite compelling genetic evidence, the underlying biological mechanism is not understood. Here, we demonstrate that UMOD risk variants directly increase UMOD expression in vitro and in vivo. We modeled this effect in transgenic mice and showed that uromodulin overexpression leads to salt-sensitive hypertension and to age-dependent renal lesions that are similarly observed in elderly subjects homozygous for UMOD risk variants. We demonstrate that the link between uromodulin and hypertension is caused by activation of the renal sodium co-transporter NKCC2. This very mechanism is relevant in humans, as pharmacological inhibition of NKCC2 is more effective in lowering BP in hypertensive patients homozygous for UMOD risk variants. Our findings establish a link between the genetic susceptibility to hypertension and CKD, the control of uromodulin expression and its role in a salt-reabsorbing tubular segment of the kidney. These data point to uromodulin as a novel therapeutic target to lower BP and preserve renal function. PMID:24185693

Trudu, Matteo; Janas, Sylvie; Lanzani, Chiara; Debaix, Huguette; Schaeffer, Céline; Ikehata, Masami; Citterio, Lorena; Demaretz, Sylvie; Trevisani, Francesco; Ristagno, Giuseppe; Glaudemans, Bob; Laghmani, Kamel; Dell’Antonio, Giacomo; Loffing, Johannes; Rastaldi, Maria P.; Manunta, Paolo

2013-01-01

270

Increase of angiotensin-converting enzyme activity and peripheral sympathetic dysfunction could contribute to hypertension development in streptozotocin-induced diabetic rats.  

PubMed

Diabetes augments the risk of hypertension. Although several factors have been implicated in the development of such hypertensive state, we designed this study to investigate blood pressure development, the activity of angiotensin-converting enzyme (ACE) in blood as well as sympathetic neurotransmission in the vas deferens of diabetic rats. We used streptozotocin (STZ)-induced diabetic rats (60 mg/kg) in order to evaluate the systolic blood pressure (SBP), ACE activity and peripheral sympathetic neurotransmission. We observed the following changes of parameters: increase of SBP, decrease of heart rate, augmentation of plasma ACE activity, enhancement of phasic and tonic vas deferens contractions elicited by electrical stimulation at 5 Hz, increase of maximal response to noradrenaline (NA) and decrease of adenosine triphosphate (ATP)-elicited contraction of vasa deferentia. The results reveal that in the development of hypertension in diabetic rats, augmentation of circulating ACE activity precedes the sympathetic dysfunction. Additionally, it seems that the purinergic and noradrenergic neurotransmission is compromised. PMID:23975725

Musial, Diego C; da Silva Júnior, Edilson D; da Silva, Regiane M; Miranda-Ferreira, Regiane; Lima-Landman, M Teresa R; Jurkiewicz, Aron; García, Antonio G; Jurkiewicz, Neide H

2013-11-01

271

Postmenopausal Hypertension  

PubMed Central

Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Hypertension is a major risk factor for cardiovascular disease. The mechanisms responsible for postmenopausal hypertension have not been completely elucidated. However, various mechanisms have been implicated to play a role. For example, there is evidence that changes in estrogen/androgen ratios favoring increases in androgens, activation of the renin-angiotensin and endothelin systems, activation of the sympathetic nervous system, metabolic syndrome and obesity, inflammation, increased vasoconstrictor eicosanoids, and anxiety and depression may be important in the pathogenesis of postmenopausal hypertension. There is also evidence that hypertension is less well controlled in aging women than in aging men, but the reasons for this gender difference is not clear. Postmenopausal hypertension is likely multifactorial. Future studies will be necessary to determine the contribution of these systems listed above in mediating postmenopausal hypertension and to design treatment strategies that encompass these mechanisms to improve the quality of life of postmenopausal women as they age. PMID:21509049

Yanes, Licy L.; Reckelhoff, Jane F.

2013-01-01

272

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

273

Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat  

PubMed Central

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·?) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·? in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·? in the MnPO contributes to the development of chronic AngII-dependent hypertension. PMID:25474089

Collister, John P.; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C.

2014-01-01

274

Angiotensin II receptor type 1-mediated vascular oxidative stress and proinflammatory gene expression in aldosterone-induced hypertension: the possible role of local renin-angiotensin system.  

PubMed

Recently, aldosterone has been shown to activate local renin-angiotensin system in vitro. To elucidate the potential role of local renin-angiotensin system in aldosterone-induced cardiovascular injury, we investigated the effects of selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL), angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide dismutase mimetic tempol (TEM) on the development of hypertension, vascular injury, oxidative stress, and inflammatory-related gene expression in aldosterone-treated hypertensive rats. The increased systolic blood pressure and vascular inflammatory changes were attenuated by cotreatment either with EPL, ARB, or TEM. Aldosterone increased angiotensin-converting enzyme expression in the aortic tissue; its effects were blocked by EPL but not by ARB or TEM. Aldosterone also increased Ang II contents in the aortic tissue in the presence of low circulating Ang II concentrations. Aldosterone induced expression of various inflammatory-related genes, whose effects were abolished by EPL, whereas the inhibitory effects of ARB and TEM varied depending on the gene. Aldosterone caused greater accumulation of the oxidant stress marker 4-hydroxy-2-neonenal in the endothelium; its effect was abolished by EPL, ARB, or TEM. Aldosterone increased mRNA levels of reduced nicotinamide adenine dinucleotide phosphate oxidase components; their effect was abolished by EPL, whereas ARB and TEM decreased only the p47phox mRNA level but not that of p22phox or gp91phox. The present findings suggest that the Ang II-dependent pathway resulting from vascular angiotensin-converting enzyme up-regulation and Ang II-independent pathway are both involved in the underlying mechanisms resulting in the development of hypertension, vascular inflammation, and oxidative stress induced by aldosterone. PMID:17218415

Hirono, Yuki; Yoshimoto, Takanobu; Suzuki, Noriko; Sugiyama, Toru; Sakurada, Maya; Takai, Shinji; Kobayashi, Naohiko; Shichiri, Masayoshi; Hirata, Yukio

2007-04-01

275

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

276

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

277

Third Trimester Maternal Plasma Total Fibronectin Levels in Pregnancy-Induced Hypertension: Results of a Tertiary Center  

Microsoft Academic Search

The aim of this study was to evaluate maternal plasma total fibronectin values in pregnancy-associated hypertension in women in the third trimester of pregnancy. A total of 125 pregnant women at the 24th week of gestation participated in this study. Nonpregnant normotensive women were included as control group (n = 30). Plasma samples for fibronectin were obtained at the 24th,

Tahsin Aydin; Füsun G. Varol; Niyazi Cenk Sayin

2006-01-01

278

Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat  

Microsoft Academic Search

Objective: Cardiovascular risk is increased among HIV-infected patients receiving antiretroviral therapy due to the development of hypertension and metabolic abnormalities. In this study, we investigated the effects of long-term treatment with zidovudine (AZT) and vitamin C, alone and in combination, on blood pressure and on the chain of events linking oxidative stress to cardiac damage in the rat. Methods: Six

Italia Papparella; Giulio Ceolotto; Laura Berto; Maurizio Cavalli; Sergio Bova; Gabriella Cargnelli; Ezia Ruga; Ornella Milanesi; Lorenzo Franco; Martina Mazzoni; Lucia Petrelli; Gastone G. Nussdorfer; Andrea Semplicini

2007-01-01

279

Role of STAT3 in angiotensin II-induced hypertension and cardiac remodeling revealed by mice lacking STAT3 serine 727 phosphorylation.  

PubMed

STAT3 is involved in protection of the heart provided by ischemic preconditioning. However, the role of this transcription factor in the heart in chronic stresses such as hypertension has not been defined. We assessed whether STAT3 is important in hypertension-induced cardiac remodeling using mice with reduced STAT3 activity due to a S727A mutation (SA/SA). Wild type (WT) and SA/SA mice received angiotensin (ANG) II or saline for 17 days. ANG II increased mean arterial and systolic pressure in SA/SA and WT mice, but cardiac levels of cytokines associated with heart failure were increased less in SA/SA mice. Unlike WT mice, hearts of SA/SA mice showed signs of developing systolic dysfunction as evidenced by reduction in ejection fraction and fractional shortening. In the left ventricle of both WT and SA/SA mice, ANG II induced fibrosis. However, fibrosis in SA/SA mice appeared more extensive and was associated with loss of myocytes. Cardiac hypertrophy as indexed by heart to body weight ratio and left ventricular anterior wall dimension during diastole was greater in WT mice. In WT+ANG II mice there was an increase in the mass of individual myofibrils. In contrast, cardiac myocytes of SA/SA+ANG II mice showed a loss in myofibrils and myofibrillar mass density was decreased during ANG II infusion. Our findings reveal that STAT3 transcriptional activity is important for normal cardiac myocyte myofibril morphology. Loss of STAT3 may impair cardiac function in the hypertensive heart due to defective myofibrillar structure and remodeling that may lead to heart failure. PMID:23364341

Zouein, Fouad A; Zgheib, Carlos; Hamza, Shereen; Fuseler, John W; Hall, John E; Soljancic, Andrea; Lopez-Ruiz, Arnaldo; Kurdi, Mazen; Booz, George W

2013-06-01

280

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

281

Preventive effects of the angiotensin-converting enzyme inhibitor, captopril, on the development of azoxymethane-induced colonic preneoplastic lesions in diabetic and hypertensive rats  

PubMed Central

Metabolic syndrome (Mets), including diabetes and hypertension, increases the risk of colorectal cancer via the induction of chronic inflammation, acceleration of oxidative stress, and activation of the renin-angiotensin system. The present study examined the possible inhibitory effects of captopril, an angiotensin-converting enzyme (ACE) inhibitor and antihypertensive drug, on the development of azoxymethane (AOM)-induced colonic premalignant lesions, aberrant crypt foci (ACF), in SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic and hypertensive rats. Male 6-week-old SHRSP-ZF rats were administered two, weekly intraperitoneal injections of AOM (20 mg/kg body weight). Following the second injection, the rats received drinking water containing captopril (8 mg/kg/day) for two weeks. At sacrifice, captopril administration significantly lowered the blood pressure and reduced the total number and size of ACF compared with those observed in the untreated group. The serum levels of angiotensin-II and the expression levels of ACE and angiotensin-II type 1 receptor mRNA on the colonic mucosa decreased following captopril treatment. Captopril also reduced the urinary 8-hydroxy-2?-deoxyguanosine levels and the serum derivatives of reactive oxygen metabolites levels, both of which are oxidative stress markers, but increased the mRNA levels of catalase, an antioxidant enzyme, in the colonic epithelium. Moreover, the expression levels of tumor necrosis factor-?, interleukin-18, monocyte chemoattractant protein-1, inducible nitric oxide synthase, vascular endothelial growth factor and proliferating cell nuclear antigen mRNA in the colonic epithelium were decreased significantly following captopril administration. These observations suggested that captopril prevents the development of ACF by inhibiting renin-angiotensin system activation and attenuating inflammation and oxidative stress in SHRSP-ZF rats. Therefore, targeting Mets-related pathophysiological conditions, including renin-angiotensin system activation, may be an effective strategy to prevent colorectal carcinogenesis in patients with Mets, particularly those with hypertension. PMID:24959250

KOCHI, TAKAHIRO; SHIMIZU, MASAHITO; OHNO, TOMOHIKO; BABA, ATSUSHI; SUMI, TAKAFUMI; KUBOTA, MASAYA; SHIRAKAMI, YOHEI; TSURUMI, HISASHI; TANAKA, TAKUJI; MORIWAKI, HISATAKA

2014-01-01

282

Preventive effects of the angiotensin-converting enzyme inhibitor, captopril, on the development of azoxymethane-induced colonic preneoplastic lesions in diabetic and hypertensive rats.  

PubMed

Metabolic syndrome (Mets), including diabetes and hypertension, increases the risk of colorectal cancer via the induction of chronic inflammation, acceleration of oxidative stress, and activation of the renin-angiotensin system. The present study examined the possible inhibitory effects of captopril, an angiotensin-converting enzyme (ACE) inhibitor and antihypertensive drug, on the development of azoxymethane (AOM)-induced colonic premalignant lesions, aberrant crypt foci (ACF), in SHRSP.Z-Lepr (fa) /IzmDmcr (SHRSP-ZF) diabetic and hypertensive rats. Male 6-week-old SHRSP-ZF rats were administered two, weekly intraperitoneal injections of AOM (20 mg/kg body weight). Following the second injection, the rats received drinking water containing captopril (8 mg/kg/day) for two weeks. At sacrifice, captopril administration significantly lowered the blood pressure and reduced the total number and size of ACF compared with those observed in the untreated group. The serum levels of angiotensin-II and the expression levels of ACE and angiotensin-II type 1 receptor mRNA on the colonic mucosa decreased following captopril treatment. Captopril also reduced the urinary 8-hydroxy-2'-deoxyguanosine levels and the serum derivatives of reactive oxygen metabolites levels, both of which are oxidative stress markers, but increased the mRNA levels of catalase, an antioxidant enzyme, in the colonic epithelium. Moreover, the expression levels of tumor necrosis factor-?, interleukin-18, monocyte chemoattractant protein-1, inducible nitric oxide synthase, vascular endothelial growth factor and proliferating cell nuclear antigen mRNA in the colonic epithelium were decreased significantly following captopril administration. These observations suggested that captopril prevents the development of ACF by inhibiting renin-angiotensin system activation and attenuating inflammation and oxidative stress in SHRSP-ZF rats. Therefore, targeting Mets-related pathophysiological conditions, including renin-angiotensin system activation, may be an effective strategy to prevent colorectal carcinogenesis in patients with Mets, particularly those with hypertension. PMID:24959250

Kochi, Takahiro; Shimizu, Masahito; Ohno, Tomohiko; Baba, Atsushi; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

2014-07-01

283

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

284

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

285

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

286

Contribution of chloride channel activation to the elevated muscular tone of the pulmonary artery in monocrotaline-induced pulmonary hypertensive rats.  

PubMed

In monocrotaline-treated rat pulmonary artery from which endothelium was removed, greater spontaneous muscular tone was observed under resting conditions than in vehicle-treated artery. The aim of the present study was to show the possible contribution of Cl- channels in the mechanism of the elevated tone. Verapamil almost completely inhibited the elevated spontaneous muscular tone by decreasing [Ca2+]i. The elevated muscular tone was also inhibited by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), a Cl- channel inhibitor. After the inhibition of muscular tone by DIDS, verapamil did not induce further relaxation. Quantitative RT-PCR analysis indicated that the mRNA levels of ClC3 and Ca2+-activated Cl- channels did not change in the pulmonary hypertensive pulmonary artery from those of vehicle-treated rats. These results suggest that the elevated muscular tone observed in the monocrotaline-induced hypertensive pulmonary artery is due to membrane depolarization of smooth muscle cells and that this phenomenon might be mediated by the activation of DIDS-sensitive Cl- channels. PMID:11488431

Nakazawa, H; Hori, M; Murata, T; Ozaki, H; Karaki, H

2001-07-01

287

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; Alarcón-Martínez, Luis; Valiente-Soriano, Francisco Javier; Ortín-Martínez, Arturo; Jiménez-López, Manuel; Avilés-Trigueros, Marcelino; Villegas-Pérez, María Paz; de la Villa, Pedro

2009-01-01

288

Common Secondary Causes of Resistant Hypertension and Rational for Treatment  

PubMed Central

Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of resistant hypertension. Several drugs can induce or exacerbate pre-existing hypertension, with non-steroidal anti-inflammatory drugs being the most common due to their wide use. Obstructive sleep apnoea and primary aldosteronism are frequently encountered in patients with resistant hypertension and require expert management. Hypertension is commonly found in patients with chronic kidney disease and is frequently resistant to treatment, while the management of renovascular hypertension remains controversial. A step-by-step approach of patients with resistant hypertension is proposed at the end of this review paper. PMID:21423678

Faselis, Charles; Doumas, Michael; Papademetriou, Vasilios

2011-01-01

289

Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution  

PubMed Central

Abstract Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule ?. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension. PMID:25610601

Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M.; Reibman, Joan

2014-01-01

290

Impaired ?-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity  

PubMed Central

?-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 IKCa/SKCa channels (TRAM-34 plus UCL1684) or BKCa channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SKCa channel was decreased in DOCA-salt arteries. The expression of BKCa channel ? subunit was increased whereas the expression of BKCa channel ? subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BKCa 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 IKCa/SKCa and/or BKCa channels activities rather than cAMP/PKA pathway. Impaired ?-AR-stimulated BKCa 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

2012-01-01

291

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

PubMed

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

292

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

293

Expression of renin-angiotensin system genes in brain structures of ISIAH rats with stress-induced arterial hypertension.  

PubMed

We studied the expression of genes encoding angiotensinogen (Agt), renin (Ren), angiotensin-converting enzyme (ACE), and type 1 angiotensin receptor (AT1A) in the hypothalamus and medulla oblongata of hypertensive ISIAH rats and normotensive WAG rats. The amount of Agt mRNA in the hypothalamus of young ISIAH rats was increased by 30% compared to WAG controls. In the medulla oblongata of young ISIAH rats, the levels of mRNA of Agt and AT1A receptor were enhanced by 60% and 24%, respectively, compared to WAG rats. In adult animals, the expression of the studied genes did not differ from the control. It is concluded that changes in gene expression of the renin-angiotensin system in brain structures of ISIAH rats may contribute to the development of hypertension. PMID:23484200

Klimov, L O; Fedoseeva, L A; Ryazanova, M A; Dymshits, G M; Markel, A L

2013-01-01

294

Cross Talk Between Endothelial and Smooth Muscle Cells in Pulmonary Hypertension Critical Role for Serotonin-Induced Smooth Muscle Hyperplasia  

Microsoft Academic Search

Background—The mechanism of pulmonary artery smooth muscle cell (PA-SMC) hyperplasia in idiopathic pulmonary artery hypertension (iPH) may involve both an inherent characteristic of PA-SMCs and abnormal control by external stimuli. We investigated the role of pulmonary microvascular endothelial cells (P-ECs) in controlling PA-SMC growth. Methods and Results—Serum-free medium of quiescent P-ECs elicited marked PA-SMC proliferation, and this effect was greater

Saadia Eddahibi; Christophe Guignabert; Anne-Marie Barlier-Mur; Laurence Dewachter; Elie Fadel; Philippe Dartevelle; Marc Humbert; Gerald Simonneau; Naïma Hanoun; Françoise Saurini; Michel Hamon; Serge Adnot

2010-01-01

295

Third trimester maternal plasma total fibronectin levels in pregnancy-induced hypertension: results of a tertiary center.  

PubMed

The aim of this study was to evaluate maternal plasma total fibronectin values in pregnancy-associated hypertension in women in the third trimester of pregnancy. A total of 125 pregnant women at the 24th week of gestation participated in this study. Nonpregnant normotensive women were included as control group (n = 30). Plasma samples for fibronectin were obtained at the 24th, 28th, and 32nd weeks of gestation from all pregnant patients. From this cohort, 10 patients met the criteria for the diagnosis of gestational hypertension and 15 women met the stringent requirements of preeclampsia, whereas 100 patients were normotensive later in gestation. Plasma total fibronectin levels were determined by radial immunodiffusion technique. Data were analyzed using the SPSS program. The mean plasma fibronectin levels of the pregnant women in whom gestational hypertension and preeclampsia developed were significantly higher at the 24th, 28th, and 32nd weeks in comparison to normotensive pregnant women (p < 0.001). However, throughout the period from the 24th to 32nd weeks of pregnancy, plasma total fibronectin levels did not exhibit a significant change in normotensive pregnant patients or in patients with preeclampsia and gestational hypertension. There was also no correlation between plasma fibronectin levels and gestational age, mean arterial pressure, birth weight, and 5-minute Apgar scores in all groups (p < 0.05). The elevated maternal plasma fibronectin level over 40 mg/dL is capable of predicting preeclampsia with a sensitivity of 73% and a specificity of 92%. These results suggest that serial plasma fibronectin measurements before 24 weeks' of gestation may be helpful in the early detection of preeclampsia in normotensive gravid women who are destined to become clinically preeclamptic. PMID:16444432

Aydin, Tahsin; Varol, Füsun G; Sayin, Niyazi Cenk

2006-01-01

296

Rats with inherited stress-induced arterial hypertension (ISIAH strain) display specific quantitative trait loci for blood pressure and for body and kidney weight on chromosome 1.  

PubMed

1. The aim of the present study was to scan chromosome 1 in the hypertensive 'inherited stress-induced arterial hypertension' (ISIAH) rat strain for the quantitative trait loci (QTL) that control basal and stress-induced arterial blood pressure (ABP) levels and weight traits. 2. Two F(2) populations of 3-4- and 6-month-old male rats derived from a cross between the normotensive Wistar albino Glaxo (WAG) and hypertensive ISIAH rats were used in the search for the QTL. To identify the QTL for blood pressure (basal and under stress) and weight traits (bodyweight, as well as the weight of the adrenals, kidney and heart), 12 polymorphic markers covering a span of 234.6 Mb on chromosome 1 were analysed. 3. In 3-4-month-old rats, QTL were found for bodyweight in the vicinity of the D1Rat76 marker (230.6 Mb; P = 0.0019; logarithm of odds (LOD) score 3.23) and for relative kidney weight in the vicinity of the D1Rat117 marker (219.3 Mb; P = 0.000992; LOD score 3.41). No QTL for blood pressure were detected on chromosome 1 in the 3-4-month-old population. 4. In 6-month-old rats, a QTL for basal ABP in the region spanning 168.0-250.4 Mb, with two peaks around the markers D1Rat168 (204.8 Mb; P = 0.00087; LOD score 3.42) and D1Rat76 (P = 0.0006; LOD score 3.34), was described. A novel QTL was found in the D1Rat54-D1Rat168 region for stress-induced blood pressure (P = 0.0014; LOD score 3.08). 5. The results provide support for the existence of age-dependent differences in the genetic control of ABP and weight traits. Chromosome 1 was characterized by four QTL: for bodyweight and relative kidney weight in 3-4-month-old F(2) (ISIAH yen WAG) rats and basal ABP and ABP under emotional (restraint) stress conditions in 6-month-old F(2) rats. The QTL for stress-induced ABP seems to be novel and specific to the ISIAH rat strain. PMID:16700878

Redina, O E; Machanova, N A; Efimov, V M; Markel, A L

2006-01-01

297

Aldosterone and stress-dependent arterial hypertension.  

PubMed

Secretory activity of the adrenal cortex and hormonal reaction to emotional stress were examined in normotensive WAG and hypertensive ISIAH rats. Under nembutal narcosis (surgical stage), secretion of corticosteroid hormones and hormonal reaction to acute stress in hypertensive rats were enhanced. In these rats, the stress-induced elevation of aldosterone secretion was most pronounced, which indicates an important contribution of this hormone to the pathogenesis of stress-dependent arterial hypertension. PMID:22808456

Antonov, E V; Markel', A L; Yakobson, G S

2011-12-01

298

Statins for Treatment of Pulmonary Hypertension  

Microsoft Academic Search

By virtue of their multiple actions, including anti-inflammatory, antiproliferative, and pro-apoptotic traits and the ability\\u000a to restore endothelial vasoactive mediator production, statins have been proposed as potential therapies for pulmonary hypertension.\\u000a In experimental studies in rats with pulmonary hypertension induced either by either monocrotaline or hypoxia, statins have\\u000a blunted the severity of pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular

John L. Faul; Peter N. Kao; Toshihiko Nishimura; Arthur Sung; Hong Hu; Ronald G. Pearl

299

Repeated gene transfer of naked prostacyclin synthase plasmid into skeletal muscles attenuates monocrotaline-induced pulmonary hypertension and prolongs survival in rats.  

PubMed

A safer, less invasive method for repeated transgene administration is desirable for clinical application of gene therapy targeting chronic diseases, including pulmonary hypertension (PH). Thus, effects of prostaglandin I2 (prostacyclin) synthase (PGIS) gene transfer by the naked DNA method into skeletal muscle were investigated in monocrotaline (MCT)-induced PH rats. A single injection of rat PGIS cDNA-encoding plasmid into thigh muscle 3 days after bupivacaine pretreatment transiently increased muscle PGIS protein expression and muscle and serum levels of a stable prostacyclin metabolite (6-keto-prostaglandin F1). The muscle 6-keto-prostaglandin F1 level peaked on day 2 but was still elevated on day 7; prostacyclin selectively increased lung cyclic AMP levels as compared with liver and kidney. MCT induced a marked rise in right ventricular (RV) systolic pressure, pulmonary arterial wall thickening, and RV hypertrophy. Repeated PGIS gene transfer every week lowered RV systolic pressure and ameliorated RV and pulmonary artery remodeling in MCT-induced PH rats. Furthermore, repeated PGIS gene transfer significantly improved the survival rate of MCT-induced PH rats. In conclusion, repeated PGIS gene transfer into skeletal muscle not only attenuated the development of PH and cardiovascular remodeling but also improved the prognosis for MCT-induced PH rats. This study may provide insight into a new treatment strategy for PH. PMID:15684702

Tahara, Nobuhiro; Kai, Hisashi; Niiyama, Hiroshi; Mori, Takahiro; Sugi, Yusuke; Takayama, Narimasa; Yasukawa, Hideo; Numaguchi, Yasushi; Matsui, Hideo; Okumura, Kenji; Imaizumi, Tsutomu

2004-12-01

300

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

301

Changes of adrenomedullin and its receptor components mRNAs expression in the brain stem and hypothalamus-pituitary-adrenal axis of stress-induced hypertensive rats.  

PubMed

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the changes in mRNAs levels of preproadrenomedullin (ppADM) gene encoding adrenomedullin (ADM) and the essential receptor components of ADM, calcitonin receptor-like receptor (CRLR), and the receptor activity modifying protein 2 and 3 (RAMP2 and RAMP3) in the medulla oblongata, hypothalamus, midbrain, pituitary gland and adrenal gland of the stress-induced hypertensive rats. It was shown that chronic foot-shock and noise stress for 15 consecutive days induced a significant increase in systolic blood pressure (SBP) and unique changes in ppADM and its receptor components mRNAs in all areas studied. As compared with the control group, the level of ppADM mRNA, normalized against a glyceraldehydes-3-phosphate dehydrogenase (GAPDH) control, was up-regulated in the hypothalamus-pituitary-adrenal (HPA) axis, but down-regulated in the medulla oblongata and midbrain (P<0.01 and P<0.05, respectively). The relative amount of CRLR mRNA was higher in the hypothalamus than that in other areas. The level of CRLR mRNA expression was significantly increased in the medulla oblongata of the stress group (P<0.01), but decreased in the midbrain (P<0.01) as well as hypothalamus(P<0.05), as compared with that of the control group. Chronic stress for 15 consecutive days produced an increase in the level of RAMP2 mRNA expression in the medulla oblongata (P<0.01) and a decrease in the adrenal gland (P<0.01), as compared with the control. No significant stress-related changes in RAMP2 mRNA were observed in the midbrain, hypothalamus and pituitary gland. The amount of RAMP3 mRNA was relatively higher in the midbrain and hypothalamus than that in the medulla oblongata, adrenal gland and adrenal gland. Stress-induced hypertensive rats exhibited an increased RAMP3 mRNA expression in the hypothalamus and pituitary gland (P<0.01 and P<0.05, respectively) and a decrease in the adrenal gland and midbrain (P<0.05). No significant stress-related change in RAMP3 mRAN was observed in the medulla oblongata. Taken together, our results indicate that the significant changes in ppADM and its receptor components mRNAs expression in the HPA axis and autonomic centers may be related to the development of the stress-induced hypertension. Nevertheless, the pathophysiological significance of brain-derived ADM and its receptors in stress and blood pressure regulation and their roles in stress-induced hypertension still await further investigation. PMID:15614422

Li, Xia; Li, Liang; Shen, Lin-Lin; Qian, Yuan; Cao, Yin-Xiang; Zhu, Da-Nian

2004-12-25

302

Resistant hypertension: underlying causes and treatment.  

PubMed

Resistant hypertension (RH) is defined as failure to achieve goal blood pressure while receiving a 3 drug regimen at optimal doses that includes a diuretic. The exact prevalence of resistant hypertension is unknown which may vary from 5% to 50%. Patient or clinician-related factors contributing to resistant hypertension include patient's non-adherence to antihypertensive therapy, White-coat effect and pseudo-hypertension and life style factors (Obesity, alcohol, smoking, dietary sodium etc). Several drugs may induce pre-existing hypertension where non-steroidal anti-inflammatory drugs are usually the most common due to their frequent use; whereas oral contraceptives, sympathomimetics (decongestants, anorectics), adrenal steroids and antineoplastic drugs targeting the vascular endothelial growth factor (VEGF) pathway has a good deal of contribution to resistant hypertension. Most common secondary causes of resistant hypertension are obstructive sleep apnea, renal artery stenosis, renal parenchymal disease, and primary aldosteronism while some uncommon causes such as pheochromocytoma, Cushing's disease, thyroid and parathyroid dysfunction; and aortic coarctation also contribute to resistant hypertension. Both pharmacological and non-pharmacological treatments are available for the management of resistant hypertension. This article reviews the prevalence, symptoms, causes and treatment of resistant hypertension. PMID:23526242

Sarwar, M S; Islam, M S; Al Baker, S M E; Hasnat, A

2013-05-01

303

Significance of echocardiographic assessment for right ventricular function after balloon pulmonary angioplasty in patients with chronic thromboembolic induced pulmonary hypertension.  

PubMed

Balloon pulmonary angioplasty (BPA) may improve hemodynamics and exercise tolerance in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We studied consecutive 25 patients with CTEPH who underwent BPA and evaluated hemodynamics by right-sided heart catheterization. Right ventricular (RV) function was assessed before and after BPA by echocardiography including speckle-tracking echocardiography and 3-dimensional echocardiography. BPA improved the mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac index. BPA also ameliorated the 3-dimentional RV volume, RV ejection fraction, and RV systolic peak strain, all of which were significantly correlated with hemodynamic parameters. The changes in cardiac index were significantly correlated with those in 3-dimentional RV volume index. Furthermore, RV dyssynchrony quantified by the RV strain analyses was ameliorated after BPA even in patients with mild pulmonary hypertension, implicating the merit of BPA in this patient population with CTEPH. BPA not only improved the hemodynamics in patients with CTEPH, but also ameliorated RV remodeling and dyssynchrony as assessed by 3-dimensional echocardiography or speckle-tracking echocardiography. Thus, the assessment of RV function may provide valuable information about the appropriate indication for BPA, its efficacy, and the therapeutic goal for patients with CTEPH. PMID:25476559

Tsugu, Toshimitsu; Murata, Mitsushige; Kawakami, Takashi; Yasuda, Risako; Tokuda, Hanako; Minakata, Yugo; Tamura, Yuichi; Kataoka, Masaharu; Hayashida, Kentaro; Tsuruta, Hikaru; Maekawa, Yuichiro; Inoue, Soushin; Fukuda, Keiichi

2015-01-15

304

Protective role of acidic pH-activated chloride channel in severe acidosis-induced contraction from the aorta of spontaneously hypertensive rats.  

PubMed

Severe acidic pH-activated chloride channel (ICl,acid) has been found in various mammalian cells. In the present study, we investigate whether this channel participates in reactions of the thoracic aorta to severe acidosis and whether it plays a role in hypertension. We measured isometric contraction in thoracic aorta rings from spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. Severe acidosis induced contractions of both endothelium-intact and -denuded thoracic aorta rings. In Wistar rats, contractions did not differ at pH 6.4, 5.4 and 4.4. However, in SHRs, contractions were higher at pH 5.4 or 4.4 than pH 6.4, with no difference between contractions at pH 5.4 and 4.4. Nifedipine, ICl,acid blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS) inhibited severe acidosis-induced contraction of aortas at different pH levels. When blocking ICl,acid, the remnant contraction was greater at pH 4.4 than pH 5.4 and 6.4 for both SHRs and Wistar rats. With nifedipine, the remnant contraction was greatly reduced at pH 4.4 as compared with at pH 6.4 and 5.4. With NPPB or DIDS, the ratio of remnant contractions at pH 4.4 and 5.4 (R4.4/5.4) was lower for SHRs than Wistar rats (all <1). However, with nifedipine, the R4.4/5.4 was higher for SHRs than Wistar rats (both >1). Furthermore, patch clamp recordings of ICl,acid and intracellular Ca(2+) measurements in smooth muscle cells confirmed these findings. ICl,acid may protect arteries against excess vasoconstriction under extremely acidic extracellular conditions. This protective effect may be decreased in hypertension. PMID:23580361

Ma, Zhiyong; Qi, Jia; Fu, Zhijie; Ling, Mingying; Li, Li; Zhang, Yun

2013-01-01

305

Effect of purified saponin mixture from Astragalus corniculatus on enzyme- and non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously hypertensive rats and normotensive rats.  

PubMed

The aim of the following study was to evaluate the effect of a purified saponin mixture (PSM), isolated from Astragalus corniculatus Bieb. (Fabaceae), on enzyme-induced and non-enzyme-induced lipid peroxidation (LPO), in liver microsomes from spontaneously hypertensive rats (SHRs) - strain Okamoto Aoki, as compared to normotensive Wistar rats (NTRs). The enzyme-induced lipid peroxidation was performed by incubating rat liver microsomes with carbonetetrachloride (CCl(4)) in the presence of NADPH. In nonenzyme-induced LPO, the microsomes were incubated with a solution of iron sulphate and ascorbinic acid (Fe(2+)/AA). The effect of PSM (196.5 microg/ml) was assessed at 20 minutes' incubation time. MDA, a product of LPO, was measured spectrophotometrically. The results of our study showed that the initial MDA quantity in SHRs was significantly higher, than in NTRs. The incubation of the microsomes from both strains with PSM (196.5 microg/ml), resulted in significant reduction of MDA level, by 25% in SHRs. In NTRs, the formation of MDA was unchanged. In enzyme-induced LPO model, PSM significantly decreased the formation of MDA, by 55% in NTRs and by 35% in SHRs, compared to the respective control groups. In the model of non-enzyme induced LPO, PSM significantly decreased the formation of MDA by 95% in NTRs and practically restored it to the control level. The MDA quantity in SHR's microsomes was reduced by 25%. According to the results of this experiment we could conclude that PSM, isolated from Astragalus corniculatus, shows antioxidant activity both in SHRs and NTRs and the effect in NTRs is more pronounced. PMID:20129766

Simeonova, R L; Vitcheva, V B; Kondeva-Burdina, M S; Krasteva, I N; Nikolov, S D; Mitcheva, M K

2010-04-01

306

Vascular Remodeling in Pulmonary Hypertension  

PubMed Central

Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

Shimoda, Larissa A; Laurie, Steven S.

2013-01-01

307

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

308

The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension  

PubMed Central

Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1R/R). These mice and littermate controls that have normal collagen degradation (Col1a1+/+) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040

Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M.; Eickhoff, Jens C.

2010-01-01

309

The Incidence of Antihypertensive Drug-induced Side Effects in Patients with Diabetes Mellitus Type 2 and Hypertension  

PubMed Central

Objective: To determine types and frequency of side effects of antihypertensive drugs in patients with diabetes mellitus (DM) type 2 and hypertension. Subjects and Methods: We performed a prospective study of 79 patients with DM type 2 and hypertension, randomly selected by systematic sampling, who were followed over a period of six months. Patients were assessed at baseline and once a month measuring following parameters: types of used antihypertensive drugs and frequency of side effects, the values (mmHg) of systolic (SBP) and diastolic blood pressure (DBP). Results: Out of 79 patients, 48/79 (60.8%) were males and 31/79 (39.2%) were females. The median age in males was 53 years (IQR=48 to 55 years), in females was 53 years (IQR=49 to 56 years). There was no statistically significant difference in median age between males and females (P=0.368). There is a statistically significant difference in the values of SBP [?2(5)=312.296, P<0.001] and DBP [?2(5)=216.051, P<0.001] over a period of six months follow-up. The drug side effects were noted in 9/79 (11.4%) patients between 1-2 months, in 6/79 (7.6%) between 2-3 months, in 1/79 (1,3%) between 3-4 months. The most common side effect was cough (11/79 or 13.9%) associated with the combination of ACE inhibitor and thiazide diuretics. In 5/79 (6.3%) patients there were reports of: flushing, palpitations, headache, dizziness and leg edema associated with Ca blockers. Conclusion: The most common side effect of antihypertensive treatment was cough (13.9%) associated with the combination of ACE inhibitor and thiazide diuretic. PMID:25648509

Loga-Zec, Svjetlana; Asceric, Mensura; Loga-Andrijic, Natasa; Kapetanovic, Berina; Zerem, Enver

2014-01-01

310

Heat stress proteins in hypertension  

SciTech Connect

It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46/sup 0/C during 5 min in a hot water bath. The cells were then labeled with (/sup 75/Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension.

Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

1986-03-05

311

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

312

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

313

The Effects of Angiotensin II and Angiotensin-(1–7) in the Rostral Ventrolateral Medulla of Rats on Stress-Induced Hypertension  

PubMed Central

We have shown that angiotensin II (Ang II) and angiotensin-(1–7) [Ang-(1–7)] increased arterial blood pressure (BP) via glutamate release when microinjected into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In the present study, we tested the hypothesis that Ang II and Ang-(1–7) in the RVLM are differentially activated in stress-induced hypertension (SIH) by comparing the effects of microinjection of Ang II, Ang-(1–7), and their receptor antagonists on BP and amino acid release in SIH and control rats. We found that Ang II had greater pressor effect, and more excitatory (glutamate) and less inhibitory (taurine and ?-aminobutyric acid) amino acid release in SIH than in control animals. Losartan, a selective AT1 receptor (AT1R) antagonist, decreased mean BP in SIH but not in control rats. PD123319, a selective AT2 receptor (AT2R) antagonist, increased mean BP in control but not in SIH rats. However, Ang-(1–7) and its selective Mas receptor antagonist Ang779 evoked similar effects on BP and amino acid release in both SIH and control rats. Furthermore, we found that in the RVLM, AT1R, ACE protein expression (western blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT2R protein, ACE2 mRNA and protein expression were significantly lower in SIH than in control rats. Mas receptor expression was similar in the two groups. The results support our hypothesis and demonstrate that upregulation of Ang II by AT1R, not Ang-(1–7), system in the RVLM causes hypertension in SIH rats by increasing excitatory and suppressing inhibitory amino acid release. PMID:23967142

Du, Dongshu; Chen, Jun; Liu, Min; Zhu, Minxia; Jing, Haojia; Fang, Jie; Shen, Linlin; Zhu, Danian; Yu, Jerry; Wang, Jin

2013-01-01

314

Age-related structural characteristics of the adrenal medulla in hypertensive NISAG rats.  

PubMed

Structural characteristics of the adrenal medulla in hypertensive NISAG rats (hereditary stress-induced arterial hypertension) were studied during various periods of postnatal ontogeny. Signs of hyperplasia of the adrenal medulla were most pronounced in adult hypertensive animals with persistent arterial hypertension, as well as during the period of late ontogeny. PMID:17603660

Buzueva, I I; Filyushina, E E; Shmerling, M D; Markel, A L; Yakobson, G S

2006-12-01

315

Amelioration of angiotensin II-induced salt-sensitive hypertension by liver-type fatty acid-binding protein in proximal tubules.  

PubMed

Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT. Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT. PMID:23940201

Osaki, Ken; Suzuki, Yusuke; Sugaya, Takeshi; Tanifuji, Chiaki; Nishiyama, Akira; Horikoshi, Satoshi; Tomino, Yasuhiko

2013-10-01

316

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

317

Effects of propranolol and atenolol on immobilization stress-induced hypertension and down-regulation of central ?-adrenoceptors in rats  

Microsoft Academic Search

Effects of chronic treatment with propranolol or atenolol on stress-induced changes in blood pressure, body weight and cerebral ?-adrenoceptors in rats were examined and compared with the effects of chronic treatment with prazosin. Immobilization stress (2 h daily for 2 weeks) induced a moderate elevation of blood pressure, loss of body weight gain and downregulation of cerebral ?-adrenoceptors, but produced

Manabu Takita; Yasuo Oda; Shigeru Kigoshi; Ikunobu Muramatsu

1995-01-01

318

Microarray analysis after umbilical cord blood derived mesenchymal stem cells injection in monocrotaline-induced pulmonary artery hypertension rats  

PubMed Central

Pulmonary arterial hypertension (PAH) is associated with structural alterations of lung vasculature. PAH is still a devastating disease needing an aggressive therapeutic approach. Despite the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs), the molecular parameters to define the stemness remain largely unknown. Using high-density oligonucleotide microarrays, the differential gene expression profiles between a fraction of mononuclear cells of human umbilical cord blood (UCB) and its MSC subpopulation were obtained. Of particular interest was a subset of 46 genes preferentially expressed at 7-fold or higher in the group treated with human UCB-MSCs. This subset contained numerous genes involved in the inflammatory response, immune response, lipid metabolism, cell adhesion, cell migration, cell differentiation, apoptosis, cell growth, transport, cell proliferation, transcription, and signal transduction. Our results provide a foundation for a more reproducible and reliable quality control using genotypic analysis for the definition of human UCB-MSCs. Therefore, our results will provide a basis for studies on molecular mechanisms controlling the core properties of human MSCs. PMID:25548719

Lee, Jae Chul; Kim, Kwan Chang; Yang, Yoon Sun; Oh, Wonil; Choi, Soo Jin

2014-01-01

319

Microarray analysis after umbilical cord blood derived mesenchymal stem cells injection in monocrotaline-induced pulmonary artery hypertension rats.  

PubMed

Pulmonary arterial hypertension (PAH) is associated with structural alterations of lung vasculature. PAH is still a devastating disease needing an aggressive therapeutic approach. Despite the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs), the molecular parameters to define the stemness remain largely unknown. Using high-density oligonucleotide microarrays, the differential gene expression profiles between a fraction of mononuclear cells of human umbilical cord blood (UCB) and its MSC subpopulation were obtained. Of particular interest was a subset of 46 genes preferentially expressed at 7-fold or higher in the group treated with human UCB-MSCs. This subset contained numerous genes involved in the inflammatory response, immune response, lipid metabolism, cell adhesion, cell migration, cell differentiation, apoptosis, cell growth, transport, cell proliferation, transcription, and signal transduction. Our results provide a foundation for a more reproducible and reliable quality control using genotypic analysis for the definition of human UCB-MSCs. Therefore, our results will provide a basis for studies on molecular mechanisms controlling the core properties of human MSCs. PMID:25548719

Lee, Jae Chul; Kim, Kwan Chang; Yang, Yoon Sun; Oh, Wonil; Choi, Soo Jin; Choe, Soo Young; Hong, Young Mi

2014-12-01

320

Perinatal 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure Sensitizes Offspring to Angiotensin II-induced Hypertension  

PubMed Central

In utero and lactational exposure of mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to cardiac hypertrophy and hydronephrosis in adulthood. We tested the hypothesis that perinatal TCDD exposure increases the susceptibility to cardiovascular disease when offspring are exposed to a common cardiovascular disease risk factor, angiotensin II (Ang II). Pregnant C57BL/6N mice were exposed to corn oil (control) or 6.0 µg/kg TCDD on gestation day 14.5. Male offspring were then exposed to a subpressor (0.1 mg/kg/d) or pressor (0.7 mg/kg/d) dose of Ang II at 3.5 mo and cardiac morphology and blood pressure analyzed, respectively. Perinatal TCDD exposure increased left ventricular cavity dilation during diastole, and wall thickness during diastole and systole. While Ang II stimulated an increase in wall thickness, the degree of increase was equivalent between control and TCDD offspring. In contrast, perinatal TCDD exposure did not alter basal blood pressure. However, Ang II increased systolic blood pressure more rapidly and to a greater degree in TCDD offspring. Further, Ang II stimulated renal myofibroblast differentiation and collagen deposition to a greater degree, and tended to increase procollagen I mRNA in TCDD offspring, compared to controls. These data suggest that perinatal TCDD exposure increases the susceptibility of offspring to renal fibrosis and hypertension in adulthood. PMID:18670907

Aragon, Andrea C.; Goens, M. Beth; Carbett, Eleanor; Walker, Mary K.

2013-01-01

321

Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD  

PubMed Central

Background Previous reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR). SHR dams were given n-3 PUFA (EPA and DHA)-enriched feed (n-6/n-3 of 1:2.7) during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY) control rats were given control-feed (n-6/n-3 of 7:1). During postnatal days (PND) 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms in both sexes. PMID:23228189

2012-01-01

322

Antioxidative Activity of the Leaf of Nelumbo nucifera Gaertn. on Oxidative Stress-Induced Erythrocyte Hemolysis in Hypertensive and Normotensive Rats  

Microsoft Academic Search

Hypertension is considered as a state of oxidative stress which contribute to several organ damages. The crude leaf of Nelumbo nucifera Gaertn. (NN extract) is traditionally used as a folk medicine, and it was reported to have antioxidant activity. The present study aimed to test our hypothesis that if there is an increase in erythrocyte lipid peroxidation in hypertensive rats,

Saengkhae C

2008-01-01

323

Disease progression in iridocorneal angle tissues of BMP2-induced ocular hypertensive mice with optical coherence tomography  

PubMed Central

Purpose The goal of the present study was to test for the first time whether glaucomatous-like disease progression in a mouse can be assessed morphologically and functionally with spectral domain optical coherence tomography (SD-OCT). Methods We monitored progressive changes in conventional outflow tissues of living mice overexpressing human bone morphogenetic protein 2 (BMP2), a model for glaucoma. Intraocular pressure (IOP) and outflow tissue morphology/Young's modulus were followed in mice for 36 days with rebound tonometry and SD-OCT, respectively. Results were compared to standard histological methods. Outflow facility was calculated from flow measurements with direct cannulation of anterior chambers subjected to three sequential pressure steps. Results Overexpression of BMP2 significantly elevated IOP in a biphasic manner over time compared to mice that overexpressed green fluorescent protein in outflow cells and naïve controls. SD-OCT revealed changes in outflow tissues overexpressing BMP2 that corresponded with the timing of the IOP phases and decreased outflow facility. In the first phase, the angle was open, but the trabecular meshwork and the cornea were thickened. OCT detected increased trabecular meshwork stiffness after provocative IOP challenges of the BMP2 eyes, which corresponded to increased collagen deposition with transmission electron microscopy. In contrast, the angle was closed in the second phase. IOP elevation over 36 days due to BMP2 overexpression resulted in significant retinal ganglion cell and axon loss. Conclusions Although not a feasible open-angle glaucoma model, the BMP2 mice were useful for demonstrating the utility of SD-OCT in following disease progression and differentiating between two forms of ocular pathology over time that resulted in ocular hypertension. PMID:25558173

Li, Guorong; Farsiu, Sina; Qiu, Jianming; Dixon, Angela; Song, Chunwei; McKinnon, Stuart J.; Yuan, Fan; Gonzalez, Pedro

2014-01-01

324

Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model  

PubMed Central

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1?, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling. PMID:25587286

Zhen, Yen-Yi; Lu, Hung-I; Sung, Pei-Hsun; Chang, Li-Teh; Tsai, Tzu-Hsien; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

2014-01-01

325

Tadalafil, a long-acting inhibitor of PDE5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats.  

PubMed

The aim of this study was to assess the effect of tadalafil (0.5, 2.5, and 10 mg/kg per day) on the progression of pulmonary arterial hypertension (PAH) in early treatment and on the survival rate in late treatment on the monocrotaline (MCT)-induced PAH rat model. Tadalafil was administered once daily to rats for 3 weeks from the day of MCT-injection or 21 days after the injection. With early treatment, tadalafil at 10 mg/kg per day prevented the development of PAH by maintaining mean pulmonary artery pressure within the normal range and attenuated right ventricular hypertrophy. With late treatment, tadalafil tended to increase the partial pressure of oxygen in arterial blood and dose-dependently improved the survival rate by 55%, 60%, and 70% at 0.5, 2.5, and 10 mg/kg per day, respectively, versus 40% in the MCT-control group. Both early and late treatments with tadalafil were associated with elevated lung cyclic guanosine monophosphate (cGMP). These results suggest that tadalafil relaxes pulmonary arteries by elevating cGMP in lungs and extend survival time by improving pulmonary hemodynamics even when treatment occurs in the late phase of PAH. Thus, it is expected that tadalafil may be an effective, once-daily treatment option in humans with PAH. PMID:19881228

Sawamura, Fusae; Kato, Masami; Fujita, Kazuhisa; Nakazawa, Takahiro; Beardsworth, Anthony

2009-11-01

326

Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME-induced hypertensive rats: a dose-dependence study.  

PubMed

We investigated the antihypertensive and antioxidant potential of vanillic acid (VA) in N(?)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) - treated adult male albino Wistar rats. Treatment of rats with L-NAME (40 mg/kg Bw for 30 days) caused a sustained increase in systolic- (SBP) and diastolic blood pressure (DBP) and significantly decreased the concentration of nitrite/nitrate (NO(x)) in plasma as compared with that in the control. Rats treated with VA restored SBP and DBP to normal level and preserve the plasma NO metabolites concentration. Moreover, VA reduced lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) and significantly restored enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase), non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma. To assess the toxicity if any of VA treatment, hepatic and renal function markers were measured. Our results showed that the effect at a dose of 50 mg/kg Bw of VA was more pronounced than that of the other two doses, 25 and 100 mg/kg Bw. These results were supported by histopathology studies. We conclude that VA possesses an antihypertensive and antioxidant activity in L-NAME-induced hypertensive rats. PMID:22005341

Kumar, Subramanian; Prahalathan, Pichavaram; Raja, Boobalan

2011-01-01

327

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

328

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

329

Low renin hypertension  

PubMed Central

Low renin hypertension is an important and often underdiagnosed cause of hypertension. It may be associated with high aldosterone levels as in Conn's syndrome or low aldosterone levels as in Liddle syndrome, and syndrome of apparent mineralocorticoid excess, glucocorticoid remediable hypertension etc. Some forms of essential hypertension are also associated with low renin levels. Hypokalemia may be an important finding in low renin hypertension. The aldosterone to renin ratio helps in correct diagnosis. The treatment varies with etiology hence an accurate diagnosis is essential. Aldosterone antagonists play an important role in medical management of some varieties of low renin hypertension. PMID:23087856

Sahay, Manisha; Sahay, Rakesh K.

2012-01-01

330

Angiotensin II-induced hypertension blunts thick ascending limb NO production by reducing NO synthase 3 expression and enhancing threonine 495 phosphorylation.  

PubMed

Thick ascending limbs reabsorb 30% of the filtered NaCl load. Nitric oxide (NO) produced by NO synthase 3 (NOS3) inhibits NaCl transport by this segment. In contrast, chronic angiotensin II (ANG II) infusion increases net thick ascending limb transport. NOS3 activity is regulated by changes in expression and phosphorylation at threonine 495 (T495) and serine 1177 (S1177), inhibitory and stimulatory sites, respectively. We hypothesized that NO production by thick ascending limbs is impaired by chronic ANG II infusion, due to reduced NOS3 expression, increased phosphorylation of T495, and decreased phosphorylation of S1177. Rats were infused with 200 ng·kg(-1)·min(-1) ANG II or vehicle for 1 and 5 days. ANG II infusion for 5 days decreased NOS3 expression by 40 ± 12% (P < 0.007; n = 6) and increased T495 phosphorylation by 147 ± 26% (P < 0.008; n = 6). One-day ANG II infusion had no significant effect. NO production in response to endothelin-1 was blunted in thick ascending limbs from ANG II-infused animals [ANG II -0.01 ± 0.06 arbitrary fluorescence units (AFU)/min vs. 0.17 ± 0.02 AFU/min in controls; P < 0.01]. This was not due to reduced endothelin-1 receptor expression. Phosphatidylinositol 3,4,5-triphosphate (PIP3)-induced NO production was also reduced in ANG II-infused rats (ANG II -0.07 ± 0.06 vs. 0.13 ± 0.04 AFU/min in controls; P < 0.03), and this correlated with an impaired ability of PIP3 to increase S1177 phosphorylation. We conclude that in ANG II-induced hypertension NO production by thick ascending limbs is impaired due to decreased NOS3 expression and altered phosphorylation. PMID:25377910

Ramseyer, Vanesa D; Gonzalez-Vicente, Agustin; Carretero, Oscar A; Garvin, Jeffrey L

2015-01-15

331

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

332

Cardiovascular hypertensive emergencies.  

PubMed

Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes. PMID:25620633

Papadopoulos, D P; Sanidas, E A; Viniou, N A; Gennimata, V; Chantziara, V; Barbetseas, I; Makris, T K

2015-02-01

333

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

334

Sympathectomy for hypertension  

Microsoft Academic Search

HERE is no need to stress unduly the seriousness of essential hypertension as a human affliction; it causes two to three times as many deaths as cancer, and it restricts the enjoyment and work of many before it kills. Essential hypertension accounts for 90 per cent. of chronically raised blood pressure. The cause of essential hypertension is at present unknown.

P. A. FitzGerald

1946-01-01

335

Chronic Central Nervous System MC3/4R Blockade Attenuates Hypertension Induced by Nitric Oxide Synthase Inhibition but Not by Angiotensin II Infusion.  

PubMed

We examined whether central melanocortin 3 and 4 receptor (MC3/4R) blockade attenuates the blood pressure (BP) responses to chronic L-NAME or angiotensin II (Ang II) infusion in Sprague-Dawley rats implanted with telemetry transmitters, venous catheters, and intracerebroventricular cannula into the lateral ventricle. After 5 days of control measurements, L-NAME (10 ?g/kg/min IV, groups 1 and 2) or Ang II (10 ng/kg/min IV, groups 3 and 4) were infused for 24 days, and starting on day 7 of L-NAME or Ang II infusion, the MC3/4R antagonist SHU-9119 (24 nmol/d, n=6/group; groups 1 and 3) or vehicle (saline 0.5 ?L/h, n=6/group; groups 2 and 4) was infused intracerebroventricularly for 10 days. A control normotensive group also received SHU-9119 for 10 days (n=5). L-NAME and Ang II increased BP by 40±3 and 56±5 mm Hg, respectively, although heart rate was slightly reduced. MC3/4R blockade doubled food intake and reduced heart rate (?40 to ?50 bpm) in all groups. MC3/4R blockade caused only a small reduction in BP in normotensive group (4 mm Hg) and no change in rats receiving Ang II, although markedly reducing BP by 21±4 mm Hg in L-NAME-treated rats. After SHU-9119 infusion was stopped, food intake, heart rate, and BP gradually returned to values observed before SHU-9119 infusion was started. Ganglionic blockade at the end of L-NAME or Ang II infusion caused similar BP reduction in both groups. These results suggest that the brain MC3/4R contributes, at least in part, to the hypertension induced by chronic L-NAME infusion but not by Ang II. PMID:25287400

da Silva, Alexandre A; do Carmo, Jussara M; Dubinion, John H; Bassi, Mirian; Mokhtarpouriani, Kasra; Hamza, Shereen M; Hall, John E

2015-01-01

336

Altered skin flowmotion in hypertensive humans.  

PubMed

Essential hypertensive humans exhibit attenuated cutaneous nitric oxide (NO)-dependent vasodilation. Using spectral analysis (fast Fourier transformation) we aimed to characterize the skin flowmotion contained in the laser-Doppler flowmetry recordings during local heating-induced vasodilation before and after concurrent pharmacological inhibition of nitric oxide synthase (NOS) in hypertensive and age-matched normotensive men and women. We hypothesized that hypertensive subjects would have lower total power spectral densities (PSDs), specifically in the frequency intervals associated with intrinsic endothelial and neurogenic control of the microvasculature. Furthermore, we hypothesized that NOS inhibition would attenuate the endothelial frequency interval. Laser-Doppler flowmetry recordings during local heating experiments from 18 hypertensive (MAP: 108±2mmHg) and 18 normotensive (MAP: 88±2mmHg) men and women were analyzed. Within site NO-dependent vasodilation was assessed by perfusion of a non-specific NOS inhibitor (N(G)-nitro-l-arginine methyl ester; l-NAME) through intradermal microdialysis during the heating-induced plateau in skin blood flow. Local heating-induced vasodilation increased total PSD for all frequency intervals (all p<0.001). Hypertensives had a lower total PSD (p=0.03) and absolute neurogenic frequency intervals (p<0.01) compared to the normotensives. When normalized as a percentage of total PSD, hypertensives had reduced neurogenic (p<0.001) and augmented myogenic contributions (p=0.04) to the total spectrum. NOS inhibition decreased total PSD (p<0.001) for both groups, but hypertensives exhibited lower absolute endothelial (p<0.01), neurogenic (p<0.05), and total PSD (p<0.001) frequency intervals compared to normotensives. These data suggest that essential hypertension results in altered neurogenic and NOS-dependent control of skin flowmotion and support the use of spectral analysis as a non-invasive technique to study vasoreactivity. PMID:24418051

Bruning, R S; Kenney, W L; Alexander, L M

2015-01-01

337

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

338

Amelioration of carbon tetrachloride-induced cirrhosis and portal hypertension in rat using adenoviral gene transfer of Akt  

PubMed Central

AIM: To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride (CCl4). METHODS: Using cre-loxp technique, we created an Ad-myr-HA-Akt virus, in which Akt is labeled by a HA tag and its expression is driven by myr promoter. Further, through measuring enzyme levels and histological structure, we determined the efficacy of this Ad-myr-HA-Akt virus in inhibiting the development of cirrhosis induced by CCl4 in rats. Lastly, using western blotting, we examined the expression levels and/or phosphorylation status of Akt, apoptotic mediators, endothelial nitric oxide synthase (eNOS), and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus. RESULTS: The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment, which was consistent with the sequence reported in the GenBank. The concentrations of Ad-myr-HA-Akt and adenoviral enhanced green fluorescent protein (Ad-EGFP) virus used in the current study were 5.5 × 1011 vp/mL. The portal vein diameter, peak velocity of blood flow, portal blood flow and congestion index were significantly increased in untreated, saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection. In contrast, these parameters in the Akt cirrhosis group were comparable to normal control group. Compared to the normal control, the liver function (Alanine aminotransferase, Aspartate aminotransferase and Albumin) was significantly impaired in the untreated, saline and Ad-EGFP cirrhosis groups. The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated, saline and Ad-EGFP cirrhosis groups. The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups. The results of HE and Van Gieson staining indicated that Akt group has better preservation of histological structure and less fibrosis than other cirrhosis groups. The percentage of apoptotic cell was greatly less in Akt cirrhosis group than in other cirrhosis groups. Akt group showed positive HA tag and an increased level of phosphorylated Akt as well as decreased levels of Fas. In contrast, Caspase-3 and Caspase-9 levels in Akt group were significantly lower than other cirrhosis groups. Noticeable decrease of DR5 and ?-SMA and increase of phosphorylated eNOS were observed in the Akt group when compared to other cirrhosis groups. The NO level in liver was significantly higher in Akt group than other cirrhosis groups, which was consistent with the level of phosphorylated eNOS in these groups. CONCLUSION: This study suggest that Ad-myr-HA-Akt virus is a useful tool to prevent CCl4-induced cirrhosis in rat model and Akt pathway may be a therapeutic target for human cirrhosis. PMID:24431897

Deng, Gang; Huang, Xiang-Jun; Luo, Hong-Wu; Huang, Fei-Zhou; Liu, Xun-Yang; Wang, Yong-Heng

2013-01-01

339

Metabolomics in hypertension.  

PubMed

Hypertension is the most prevalent chronic medical condition and a major risk factor for cardiovascular morbidity and mortality. In the majority of hypertensive cases, the underlying cause of hypertension cannot be easily identified because of the heterogeneous, polygenic and multi-factorial nature of hypertension. Metabolomics is a relatively new field of research that has been used to evaluate metabolic perturbations associated with disease, identify disease biomarkers and to both assess and predict drug safety and efficacy. Metabolomics has been increasingly used to characterize risk factors for cardiovascular disease, including hypertension, and it appears to have significant potential for uncovering mechanisms of this complex disease. This review details the analytical techniques, pre-analytical steps and study designs used in metabolomics studies, as well as the emerging role for metabolomics in gaining mechanistic insights into the development of hypertension. Suggestions as to the future direction for metabolomics research in the field of hypertension are also proposed. PMID:24675680

Nikolic, Sonja B; Sharman, James E; Adams, Murray J; Edwards, Lindsay M

2014-06-01

340

Descriptive epidemiology of chronic hypertension, gestational hypertension, and preeclampsia in New York State, 1995-2004.  

PubMed

We examined social, demographic, and behavioral predictors of specific forms of hypertensive disorders in pregnancy in New York State. Administrative data on 2.3 million births over the period 1995-2004 were available for New York State, USA, with linkage to birth certificate data for New York City (964,071 births). ICD-9 hospital discharge diagnosis codes were used to assign hypertensive disorders hierarchically as chronic hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia (eclampsia/severe or mild), or gestational hypertension. Sociodemographic and behavioral predictors of these outcomes were examined separately for upstate New York and New York City by calculating adjusted odds ratios. The most commonly diagnosed conditions were preeclampsia (2.57 % of upstate New York births, 3.68 % of New York City births) and gestational hypertension (2.46 % of upstate births, 1.42 % of New York City births). Chronic hypertension was much rarer. Relative to non-Hispanic Whites, Hispanics in New York City and Black women in all regions had markedly increased risks for all hypertensive disorders, whereas Asian women were at consistently decreased risk. Pregnancy-associated conditions decreased markedly with parity and modestly among smokers. A strong positive association was found between pre-pregnancy weight and risk of hypertensive disorders, with slightly weaker associations among Blacks and stronger associations among Asians. While patterns of chronic and pregnancy-induced hypertensive disorders differed, the predictors of gestational hypertension and both mild and severe preeclampsia were similar to one another. The increased risk for Black and some Hispanic women warrants clinical consideration, and the markedly increased risk with greater pre-pregnancy weight suggests an opportunity for primary prevention among all ethnic groups. PMID:23793484

Savitz, David A; Danilack, Valery A; Engel, Stephanie M; Elston, Beth; Lipkind, Heather S

2014-05-01

341

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

342

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

343

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

344

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

345

Contribution of the medial amygdaloid nucleus to the development of hypertension in spontaneously hypertensive rats.  

PubMed

We previously demonstrated involvement of the medial amygdaloid nucleus in restraint stress-induced pressor responses in rats. In this study, neuronal perikarya in the medial amygdaloid nucleus of 4-week-old spontaneously hypertensive rats (SHR) were selectively destroyed with ibotenic acid. Bilateral lesions of the medial amygdaloid nucleus attenuated the development of hypertension in SHR. Body weight gain was not different between lesioned and sham-lesioned SHR throughout the experimental periods. These data suggest that neurons in the medial amygdaloid nucleus may be involved in the development of hypertension in SHR. PMID:15245793

Fukumori, Ryuji; Nishigori, Yusuke; Goshima, Yoshio; Kubo, Takao

2004-07-22

346

Angiotensin II AT(1) receptor blockade selectively enhances brain AT(2) receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats.  

PubMed

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT(1) receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT(1) receptor binding in the median eminence and basolateral amygdala, increased AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT(1) receptor blockade reduced AT(1) receptor binding in all areas studied and enhanced AT(2) receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT(1) binding after stress, and prevented the stress-induced AT(2) receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT(1) blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT(1) receptors, selectively increased central AT(2) receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT(1) and AT(2) receptors in the regulation of the stress response, and the hypothesis that AT(1) receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties. PMID:18609298

Bregonzio, C; Seltzer, A; Armando, I; Pavel, J; Saavedra, J M

2008-11-01

347

Severe hypertension in elapid envenomation  

PubMed Central

Snakebite is not an uncommon medical emergency in India; however, symptoms of autonomic dysfunction in snakebite are rare. The elapid snake envenomation is a frequent occurrence in India, and the krait bite is prevalent in the south Indian region. Here, we present three cases of snakebite with severe hypertension and requiring intravenous nitroglycerin (NTG). As the level of blood pressure (BP) decreased significantly following antisnake venom (ASV) injection in all three cases, it is likely that snake venom-induced dysautonomia might have contributed to severe hypertension in such patients. Clinical and therapeutic challenges of these cases are highlighted, so that practitioners coping with medical emergencies in resource-limited situations can consider snake (krait) bite in the differential diagnosis, and also manage effectively according to corroborative clinical evidences. PMID:24023478

Meenakshisundaram, Ramachandran; Senthilkumaran, Subramanian; Grootveld, Martin; Thirumalaikolundusubramanian, Ponniah

2013-01-01

348

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension  

Microsoft Academic Search

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to

Robert P. Mecham; Loren A. Whitehouse; David S. Wrenn; William C. Parks; Gail L. Griffin; Robert M. Senior; Edmond C. Crouch; Kurt R. Stenmark; Norbert F. Voelkel

1987-01-01

349

[Theoretical considerations and comments on the physiopathology in renovascular hypertension].  

PubMed

The researches performed during the last four decades did not elucidate completely the pathogenic mechanism of the renovascular hypertension. The present knowledge considers that the origins of renovascular hypertension are the imbalance between the renal hypotensive system located in the medullar renal site (antihypertensive and hypotensive substances) and the renal hypertensive system (renin-angiotensin-aldosterone) located cortically. As an additional mechanism in producing hypertension is involved the disorder of hydro electrolytic metabolism, as a result of decreased excretory function, inducing an increase of plasmatic natrium level, of volemia and interstitial liquid. PMID:19274913

Burnei, Gh; Grigorean, V T; Gavriliu, St; Du?escu, S; Georgescu, I; Iacobini, M; Vlad, C; Stoian, A R; Burnei, A; Neac?u, C M

2008-01-01

350

Portopulmonary hypertension: An update.  

PubMed

Portopulmonary hypertension represents a serious lung vascular disorder, defined as the presence of pulmonary arterial hypertension that is associated with portal hypertension, with or without the presence of significant liver disease. Transthoracic echocardiography represents the single best initial tool for the diagnostic evaluation in portopulmonary hypertension, and right heart catheterization remains the gold standard for definitive diagnosis. Despite the lack of randomized controlled trials in portopulmonary hypertension, some therapies have demonstrated improvements in cardiopulmonary haemodynamics and right ventricular function as described in case reports and case series. Specialists should be able to recognize indications and contraindications for liver transplantation in the setting of portopulmonary hypertension, and this review focuses on the appropriate diagnostic approach and current advances in medical therapies. Recognition of patients eligible for liver transplantation is needed to improve quality of life and survival. PMID:25523363

Porres-Aguilar, Mateo; Mukherjee, Debabrata

2015-02-01

351

Rod-Like Microglia Are Restricted to Eyes with Laser-Induced Ocular Hypertension but Absent from the Microglial Changes in the Contralateral Untreated Eye  

PubMed Central

In the mouse model of unilateral laser-induced ocular hypertension (OHT) the microglia in both the treated and the normotensive untreated contralateral eye have morphological signs of activation and up-regulation of MHC-II expression in comparison with naïve. In the brain, rod-like microglia align to less-injured neurons in an effort to limit damage. We investigate whether: i) microglial activation is secondary to laser injury or to a higher IOP and; ii) the presence of rod-like microglia is related to OHT. Three groups of mice were used: age-matched control (naïve, n=15); and two lasered: limbal (OHT, n=15); and non-draining portion of the sclera (scleral, n=3). In the lasered animals, treated eyes as well as contralateral eyes were analysed. Retinal whole-mounts were immunostained with antibodies against, Iba-1, NF-200, MHC-II, CD86, CD68 and Ym1. In the scleral group (normal ocular pressure) no microglial signs of activation were found. Similarly to naïve eyes, OHT-eyes and their contralateral eyes had ramified microglia in the nerve-fibre layer related to the blood vessel. However, only eyes with OHT had rod-like microglia that aligned end-to-end, coupling to form trains of multiple cells running parallel to axons in the retinal surface. Rod-like microglia were CD68+ and were related to retinal ganglion cells (RGCs) showing signs of degeneration (NF-200+RGCs). Although MHC-II expression was up-regulated in the microglia of the NFL both in OHT-eyes and their contralateral eyes, no expression of CD86 and Ym1 was detected in ramified or in rod-like microglia. After 15 days of unilateral lasering of the limbal and the non-draining portion of the sclera, activated microglia was restricted to OHT-eyes and their contralateral eyes. However, rod-like microglia were restricted to eyes with OHT and degenerated NF-200+RGCs and were absent from their contralateral eyes. Thus, rod-like microglia seem be related to the neurodegeneration associated with HTO. PMID:24367610

de Hoz, Rosa; Gallego, Beatriz I.; Ramírez, Ana I.; Rojas, Blanca; Salazar, Juan J.; Valiente-Soriano, Francisco J.; Avilés-Trigueros, Marcelino; Villegas-Perez, Maria P.; Vidal-Sanz, Manuel; Triviño, Alberto; Ramírez, José M.

2013-01-01

352

A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice  

PubMed Central

Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5–2.5 mg/kg, i.p.) reduces body and brain temperature by 2–5°C in 15–30 min in a dose-dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ?30–40% when PIH therapy is initiated either immediately after stroke induction or after 30–60 min delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3 activation, and TUNEL-positive cells in the peri-infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS-201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS-201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries. Choi, K.-E., Hall, C. L., Sun, J.-M., Wei, L., Mohamad, O., Dix, T. A., Yu, S. P. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. PMID:22459147

Choi, Ko-Eun; Hall, Casey L.; Sun, Jin-Mei; Wei, Ling; Mohamad, Osama; Dix, Thomas A.; Yu, Shan P.

2012-01-01

353

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

354

Hypertensive emergencies in pregnancy.  

PubMed

Hypertensive disorders of pregnancy complicate 7% to 10% of pregnancies and are among the major causes of maternal and perinatal morbidity and mortality. Recently American College of Obstetricians and Gynecologists Taskforce on Hypertension during Pregnancy modified the diagnosis and management of hypertension in pregnancy, recommending prompt diagnosis, admission, close monitoring, and treatment. They strive to decrease maternal mortality and systemic complications. Labetalol, hydralazine, or nifedipine are considered first-line treatment, and either can be used to stabilize the patient with similar outcomes. Definite treatment is delivery of the fetus and should be considered based on the etiology of the hypertensive crisis and gestational age. PMID:25314092

Vadhera, Rakesh B; Simon, Michelle

2014-12-01

355

Effect of ACE Inhibitor on DOCA-Salt- and Aortic Coarctation-Induced Hypertension in Mice Do Kinin B2 Receptors Play a Role?  

Microsoft Academic Search

Kinins have been shown to play an important role in the cardioprotective effect of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusion. However, it is controversial as to whether kinins oppose the hypertensinogenic effect of deoxycorticosterone acetate plus salt (DOCA-salt) or aortic coarctation and whether they mediate both chronic antihypertensive and cardiac antihypertrophic effects of ACEi in hypertension. Using normal

Nour-Eddine Rhaleb; Hongmei Peng; Marcos E. Alfie; Edward G. Shesely; Oscar A. Carretero

356

Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine  

Microsoft Academic Search

Following oral administration of methionine in high doses to normotensive (NR) and spontaneously hypertensive (SHR) rats, its degradation product, homocysteine (HC), which is markedly elevated in serum, exerts an angiotoxic action directed to the aorta. This is accompanied by considerable loss of endothelium and degeneration, partly with dissolution of the media cells with formation of characteristic processes of the degenerating

D. Matthias; C.-H. Becker; R. Riezler; P. M. Kindling

1996-01-01

357

HYPAZ: Hypertension Induced by Pazopanib  

ClinicalTrials.gov

Renal Cell Carcinoma; Soft Tissue Sarcoma; Glioblastoma; Ovarian Cancer; Cervical Cancer; Breast Cancer; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Pancreatic Cancer; Melanoma; Gastrointestinal Cancer

2013-05-16

358

Peculiarities of active avoidance conditioning in rats with various forms of inherited arterial hypertension.  

PubMed

Peculiarities of active avoidance conditioning were studied in NISAG rats (hereditary stress-induced arterial hypertension) and spontaneously hypertensive SHR rats. Conditioning was successful in 90% normotensive Wistar rats and in only 9.1% NISAG rats. Hypertensive SHR rats were intermediate between Wistar and NISAG rats by their learning capacity (66.7%). Our results suggest that differences in learning capacity of hypertensive rats are determined by genetic characteristics of animal behavior and emotional state, rather than blood pressure elevation. PMID:17415422

Loskutova, L V; Filatov, A V; Dubrovia, N I; Markel', A L

2006-10-01

359

[Comparative analysis of conditioned passive avoidance retention in rats with different forms of inherited arterial hypertension].  

PubMed

Comparing behavioral traits of anxiety in elevated plus-maze and retention of passive avoidance response in two rat strains with hereditary arterial hypertension ISIAH (inherited stress induced arterial hypertension) and SHR (spontaneously hypertensive rats) has shown the following. The SHR rats demonstrate impairment in retrieval of passive avoidance, hyperactivity and low anxiety. ISIAH rats showned better avoidance performance, average level of anxiety and activity. The interdependence of two pathologies: hypertension and memory impairment is discussed. PMID:16813150

Loskutova, L V; Dubrovina, N I; Markel', A L

2006-04-01

360

IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.  

PubMed

Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient 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 cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype. PMID:25248835

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

2014-12-01

361

Hypertension Management: An Update  

PubMed Central

Hypertension is a significant and costly public health problem. It is a major, but modifiable contributor for the development of cardiovascular disease. Randomized controlled trials have shown that controlling hypertension reduces the risk of stroke, coronary artery disease, congestive heart failure, end-stage renal disease, peripheral vascular disease, as well as overall mortality. The risk of developing these hypertension-related complications is continuous, starting at a blood pressure level as low as 115/75 mm Hg. Despite the inherent health risks associated with uncontrolled hypertension, elevated blood pressure remains inadequately treated in the majority of patients. This article reviews guidelines for optimal evaluation of hypertension and current therapeutic options available to combat this common yet pervasive disease. PMID:25126308

Nguyen, Quang; Dominguez, Joann; Nguyen, Loida; Gullapalli, Nageshwara

2010-01-01

362

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

363

Pulmonary hypertension in ? thalassaemia.  

PubMed

Pulmonary hypertension is one of the leading causes of morbidity and mortality in patients with haemolytic disorders and is a frequent finding in echocardiographic screening of patients with ? thalassaemia. Substantial progress has been made in understanding of the multifactorial pathophysiology of pulmonary hypertension in ? thalassaemia. Haemolysis, reduced nitric oxide bioavailability, iron overload, and hypercoagulopathy are among the main pathogenetic mechanisms. Various disease-directed therapeutic methods, such as transfusion, chelation, and splenectomy, have important roles in the development of pulmonary hypertension in ? thalassaemia. Studies investigating the prevalence of pulmonary hypertension in ? thalassaemia are mostly based on echocardiographic findings, and are thus limited by the scarcity of information derived from right heart catheterisation. Invasive pulmonary haemodynamic data are needed to clarify the true prevalence of pulmonary hypertension in ? thalassaemia, to better understand the underlying pathophysiology and risk factors, and to define the optimum therapy for this devastating complication. PMID:24429247

Anthi, Anastasia; Orfanos, Stylianos E; Armaganidis, Apostolos

2013-08-01

364

Diaphragm muscle fiber weakness in pulmonary hypertension  

Microsoft Academic Search

RATIONALE: Recently it was suggested that patients with pulmonary hypertension (PH) suffer from inspiratory muscle dysfunction. However, the nature of inspiratory muscle weakness in PH remains unclear. OBJECTIVES: To assess whether alterations in contractile performance and in morphology of the diaphragm underlie inspiratory muscle weakness in PH. METHODS: PH was induced in Wistar rats by a single injection of monocrotaline

F. S. de Man; H. W. H. van Hees; M. L. Handoko; H. W. M. Niessen; I. Schalij; M. Humbert; P. Dorfmuller; O. Mercier; H. J. Bogaard; P. E. Postmus; N. Westerhof; G. J. Stienen; W. J. van der Laarse; A. Vonk-Noordegraaf; C. A. C. Ottenheijm

2011-01-01

365

Chronic hypertension aggravates heat stress induced cognitive dysfunction and brain pathology: an experimental study in the rat, using growth hormone therapy for possible neuroprotection.  

PubMed

Hyperthermia following heat stress results in profound brain edema formation and damage to the central nervous system (CNS). However, whether acute or chronic diseases such as cardiovascular, endocrine, or metabolic ailments further influence the vulnerability of human populations to heat-related deaths is still unclear. In this investigation, we examined the effect of hyperthermia on chronic hypertensive rats. The influence of growth hormone (GH) as a therapy to attenuate brain dysfunction was also evaluated. Subjecting rats to 4 h of heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator resulted in profound impairment of motor and cognitive functions, breakdown of the blood-brain barrier (BBB), reduction in regional cerebral blood flow (CBF), edema formation, and brain damage. These effects were further aggravated when chronic hypertensive rats (two-kidney, one-clip model for 4 weeks) were subjected to similar hyperthermic conditions (38 degrees C for 4 h). Interestingly, the behavioral alterations and impairment of motor and cognitive functions in hypertensive rats were much worse than those in the normotensive animals subjected to heat stress. Pretreatment with GH (50 microg/kg/min i.v. for 60 min, before heat stress) significantly attenuated behavioral and cognitive deficits in normotensive rats and reduced the BBB dysfunction and brain pathology. On the other hand, similar treatment with GH in hypertensive animals only mildly reduced brain damage or cognitive dysfunction after heat stress. These novel observations indicate that patients suffering from various chronic diseases respond differently to various health hazards such as hyperthermia and to other neuroprotective agents. PMID:18077561

Muresanu, Dafin F; Sharma, Hari S

2007-12-01

366

In vivo administration of d-arginine: effects on blood pressure and vascular function in angiotensin II-induced hypertensive rats  

Microsoft Academic Search

Objective: We tested the hypothesis that d-arginine (d-Arg), which is not a substrate for nitric oxide synthase but scavenges reactive oxygen in vitro, is protective in vivo. Methods: Rats were made hypertensive by administering angiotensin II (Ang II) (0.7mgkg?1 per day) for 7 days (Ang II group). Two other groups additionally received either 3mmol d-Arg (Ang II + d-Arg group)

Gerald Wölkart; Heike Stessel; Friedrich Brunner

2004-01-01

367

Earthquake-Induced Potentiation of Acute Risk Factors in Hypertensive Elderly Patients: Possible Triggering of Cardiovascular Events After a Major Earthquake  

Microsoft Academic Search

Objectives. We sought to investigate the potentiation of acute risk factors after the Hanshin-Awaji earthquake (7.2 on the Richter scale).Background. The frequency of cardiovascular events increases just after a major earthquake, but the causative factors have not been fully investigated.Methods. We studied the changes in cardiovascular risk factors in 42 elderly outpatients with well-controlled hypertension living near the epicenter (Awaji-Hokudan

Kazuomi Kario; Takefumi Matsuo; Hiroko Kobayashi; Katsuichirou Yamamoto; Kazuyuki Shimada

1997-01-01

368

RhoA GTPase-Induced Ocular Hypertension in a Rodent Model Is Associated with Increased Fibrogenic Activity in the Trabecular Meshwork.  

PubMed

Ocular hypertension arising from increased resistance to aqueous humor (AH) outflow through the trabecular meshwork is a primary risk factor for open-angle glaucoma, a leading cause of blindness. Ongoing efforts have found little about the molecular and cellular bases of increased resistance to AH outflow through the trabecular meshwork in ocular hypertension patients. To test the hypothesis that dysregulated Rho GTPase signaling and a resulting fibrotic activity within the trabecular meshwork may result in ocular hypertension, we investigated the effects of expressing a constitutively active RhoA GTPase (RhoAV14) in the AH outflow pathway in Sprague-Dawley rats by using lentiviral vector-based gene delivery. Rats expressing RhoAV14 in the iridocorneal angle exhibited a significantly elevated intraocular pressure. Elevated intraocular pressure in the RhoAV14-expressing rats was associated with fibrotic trabecular meshwork and increased levels of F-actin, phosphorylated myosin light chain, ?-smooth muscle actin, collagen-1A, and total collagen in the trabecular AH outflow pathway. Most of these changes were ameliorated by topical application of Rho kinase inhibitor. Human autopsy eyes from patients with glaucoma exhibited significant increases in levels of collagen-1A and total collagen in the trabecular AH outflow pathway. Collectively, these observations indicate that increased fibrogenic activity because of dysregulated RhoA GTPase activity in the trabecular AH outflow pathway increases intraocular pressure in a Rho kinase-dependent manner. PMID:25499974

Pattabiraman, Padmanabhan P; Rinkoski, Tommy; Poeschla, Eric; Proia, Alan; Challa, Pratap; Rao, Ponugoti V

2015-02-01

369

Low Fibronectin in Portal Hypertension  

Microsoft Academic Search

We have measured plasma fibronectin in 28 patients with well-compensated chronic liver disease, 4 patients with non-cirrhotic portal hypertension and 6 patients who have undergone shunt surgery for the relief of portal hypertension and splenectomy. 17 patients with portal hypertension had significantly lower levels of fibronectin (207 ± 54; mean ± SD) compared with 15 patients without portal hypertension (315

P. N. Foster; Margaret Bowen; P. D. Howdle; M. S. Losowsky

1983-01-01

370

Hypertension: physiology and pathophysiology.  

PubMed

Despite major advances in understanding the pathophysiology of hypertension and availability of effective and safe antihypertensive drugs, suboptimal blood pressure (BP) control is still the most important risk factor for cardiovascular mortality and is globally responsible for more than 7 million deaths annually. Short-term and long-term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long-term regulation of BP, and abnormal renal-pressure natriuresis is present in all forms of chronic hypertension. Impaired renal-pressure natriuresis and chronic hypertension can be caused by intrarenal or extrarenal factors that reduce glomerular filtration rate or increase renal tubular reabsorption of salt and water; these factors include excessive activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, increased formation of reactive oxygen species, endothelin, and inflammatory cytokines, or decreased synthesis of nitric oxide and various natriuretic factors. In human primary (essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive weight gain and dietary factors appear to play a major role since hypertension is rare in nonobese hunter-gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene-environment interactions that may also contribute to hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of hypertension. PMID:23720252

Hall, John E; Granger, Joey P; do Carmo, Jussara M; da Silva, Alexandre A; Dubinion, John; George, Eric; Hamza, Shereen; Speed, Joshua; Hall, Michael E

2012-10-01

371

Albuminuria of hypertensive patients.  

PubMed

Renal dysfunction as a consequence of malignant hypertension has been recognized for decades in patients with essential hypertension. It has been shown only recently, however, that albuminuria (including underlying albuminuria not detectable by conventional tests, i.e. microalbuminuria) has emerged as a frequent sequela of essential hypertension. Furthermore, renal dysfunction of the elderly as a result of ischemic nephropathy, in the absence of malignant hypertension, has turned out to be an important long-term outcome in the patient with essential hypertension. The presence of albuminuria is a strong predictor of cardiovascular events. Albuminuria is associated with more severe hypertension and with evidence of more advanced target organ damage (e.g. LVH). It is more prevalent in the elderly. It is unknown whether the predictive value of albuminuria reflects its association with more severe hypertension and end-organ damage, or whether albuminuria serves as an indicator of capillary leakiness which causes detectable abnormalities in the renal microcirculation but reflects more generalized endothelial barrier dysfunction predisposing to accelerated atherogenesis. PMID:1295707

Rambausek, M; Fliser, D; Ritz, E

1992-01-01

372

Treatment of the elderly hypertensive patient.  

PubMed

Changes due to aging of the cardiovascular system play an important role in the development of hypertension and its complications in the elderly. As shown in recent experimental studies in rats, the arterial changes that normally take place resemble those resulting from hypertension. They may be preventable by maintenance of low blood pressures and may be secondary to prolonged hemodynamic effects on the artery wall. The major hemodynamic consequences of aging in man include an increase in total peripheral vascular resistance, which occurs as a result of both arterial and arteriolar disease. Other features with potentially important therapeutic implications in the elderly include an increased tendency for left ventricular dysfunction and cardiac arrhythmias, decreased baroreceptor sensitivity, and atherosclerosis-induced reduction of blood flow to vital organs. Older patients also tend to have a reduced fluid volume and an abnormal distribution and metabolism of drugs. These factors lead to greater sensitivity to potential side effects and, thus, greater difficulty in managing their hypertension. Diuretics, beta blockers, and calcium channel blockers appear to be the most useful initial antihypertensive drugs in the elderly. The cardioprotective effects of beta blockers and the desirable hemodynamic action of calcium antagonists provide compelling justification for their use in many patients. Centrally acting sympatholytic drugs such as methyldopa, clonidine, and guanabenz are useful as second-step agents, usually in combination with a diuretic. In the presence of moderate to severe diastolic hypertension, hydralazine, captopril, and minoxidil may have value, but such potent agents should generally be avoided with isolated systolic hypertension. In elderly hypertensive patients with other complicating diseases, sufficient alternative treatment options are now available to allow tailoring of therapy to the special needs of each patient, thereby minimizing adverse reactions to therapy. However, relatively low doses of medications and conservative therapeutic objectives are usually necessary, particularly in patients with isolated systolic hypertension in whom the benefits of treatment are still to be determined. PMID:6148885

Chobanian, A V

1984-08-31

373

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

374

Cardiovascular consequences of pulmonary hypertension.  

PubMed

Pulmonary hypertension occurs when pulmonary vascular pressures are elevated. Pulmonary arterial hypertension is associated with occlusion of the pulmonary arterial tree, while pulmonary venous hypertension is seen when pulmonary vein outflow is impeded. Cardiovascular consequences are common with pulmonary hypertension, regardless of the underlying pathogenesis and whether management is complex. However, there are a number of interventions that may improve quality of life and survival of pulmonary hypertension. This article discusses current recommendations for diagnosis and management. PMID:18249223

Bauldoff, Gerene S; Housten-Harris, Traci; Nunley, David R

2008-03-01

375

Orexin, cardio-respiratory function, and hypertension  

PubMed Central

In this review we focus on the role of orexin in cardio-respiratory functions and its potential link to hypertension. (1) Orexin, cardiovascular function, and hypertension. In normal rats, central administration of orexin can induce significant increases in arterial blood pressure (ABP) and sympathetic nerve activity (SNA), which can be blocked by orexin receptor antagonists. In spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can significantly lower blood pressure under anesthetized or conscious conditions. (2) Orexin, respiratory function, and central chemoreception. The prepro-orexin knockout mouse has a significantly attenuated ventilatory CO2 chemoreflex, and in normal rats, central application of orexin stimulates breathing while blocking orexin receptors decreases the ventilatory CO2 chemoreflex. Interestingly, SHRs have a significantly increased ventilatory CO2 chemoreflex relative to normotensive WKY rats and blocking both orexin receptors can normalize this exaggerated response. (3) Orexin, central chemoreception, and hypertension. SHRs have higher ABP and SNA along with an enhanced ventilatory CO2 chemoreflex. Treating SHRs by blocking both orexin receptors with oral administration of an antagonist, almorexant (Almxt), can normalize the CO2 chemoreflex and significantly lower ABP and SNA. We interpret these results to suggest that the orexin system pa