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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blood pressure reduction is the most significant factor in delaying onset and progression of renal disease. Blockade of the renin-angiotensin system (RAS) using angiotensin-converting enzyme inhibitors (ACEIs) delays renal disease progression. More recently, agents that block the RAS by preventing angiotensin II from binding to its subtype 1 receptor (ARBs) have been developed in an effort to prevent deleterious consequences of pathologic levels of angiotensin II and to reduce the adverse effects of RAS blockade associated with ACEIs. Human studies with a variety of ARBs have clearly demonstrated the antihypertensive and antiproteinuric efficacy of these agents in patients with progressive renal diseases. Moreover, the effects of ARBs are similar or identical to those of ACEIs. Ongoing long-term clinical trials are designed to determine whether ARBs also preserve renal function similar to ACEIs. Specifically, the role of ARBs in patients with hypertension and type 2 diabetes is being evaluated in 3 large trials, including Appropriate Blood Pressure Control in Diabetes-Part 2 With Valsartan, the Losartan Renal Protection Study, and the Irbesartan Diabetic Nephropathy Trial. Definitive evidence of the long-term protective effects of ARBs in chronic progressive renal disease is expected from these important studies.
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PMID:Angiotensin II subtype 1 receptor blockers and renal function. 1142 96

Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18,119 patients were screened and 15,314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease.
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PMID:Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation. 1146 64

Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor subtype, is an efficacious, orally active, blood pressure-lowering agent used in hypertensive patients. Given that aminopeptidases (APs) play a major role in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied the effect of valsartan on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and medulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased soluble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertension. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-related decreased activity in clipped and non-clipped kidneys of both sham-operated and hypertensive animals. These results suggest a functional relationship between the AT(1) receptor and vasopressin-degrading activity.
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PMID:Effect of valsartan on angiotensin II- and vasopressin-degrading activities in the kidney of normotensive and hypertensive rats. 1156 Dec 17

The aim of this investigation was to evaluate the influence of a high-salt diet (HSD) on the effects of valsartan, an angiotensin II type 1 (AT(1)) receptor antagonist, on carotid arterial stiffness and structure in spontaneous hypertensive rats (SHR). Carotid arterial stiffness was studied in SHR receiving a HSD or a normal-salt diet (NSD) from the 10th to 20th week of age. Within each of the 2 groups, the animals received treatment with either placebo or valsartan (30 mg. kg(-1). d(-1)) administered on the 4th to 20th week of age. Arterial pressure, wall stress, incremental elastic modulus (Einc), medial cross-sectional area, and EIIIA fibronectin isoform were significantly increased in placebo-HSD rats compared with placebo-NSD rats with no change in the ratio of collagen to elastin. Valsartan reduced mean arterial pressure in both NSD and HSD rats but reduced pulse pressure only in NSD rats. In NSD rats, valsartan reduced Einc and medial cross-sectional area. In HSD, valsartan increased Einc and did not modify medial cross-sectional area and fibronectin. In valsartan-treated rats, the ratio of collagen to elastin was greater in HSD than in NSD rats. In conclusion, the effects of AT(1) blockade are greatly influenced by salt intake in SHR. Despite a reduction in mean arterial pressure in HSD rats, AT(1) blockade was not able to prevent the effects of a HSD on pulse pressure, carotid artery stiffness, and hypertrophy.
Hypertension 2001 Sep
PMID:Effects of valsartan on mechanical properties of the carotid artery in spontaneously hypertensive rats under high-salt diet. 1156 19

The beneficial effects of anti-hypertensive agents on the cardiovascular system can be counterbalanced by the induction of metabolic disorders, such as hyperlipidaemia. The present trial evaluated the effect of the angiotensin II receptor antagonist, valsartan, on the lipid profile and glucose metabolism in patients with mild-to-moderate hypertension. This was a multicentre, randomized, double-blind, placebo-controlled study with a 3-week dietary run-in period under placebo; thereafter, patients received either valsartan 80 mg orally once daily or placebo for 12 weeks. A total of 123 patients were randomized, of whom 112 patients completed the study. Valsartan significantly lowered systolic blood pressure by 14.1 +/- 12.8 mmHg and diastolic blood pressure by 9.0 +/- 6.6 mmHg. In the placebo group, the corresponding values were 7.8 +/- 14.9 mmHg and 6.2 +/- 7.3 mmHg, respectively. Additionally, in the valsartan group, there was a significant decrease in levels of both low-density lipoprotein (LDL) cholesterol (valsartan, -6.3 +/- 24.9 mg/dl; placebo, +4.2 +/- 27.0 mg/dl) and total cholesterol (valsartan, -7.1 +/- 28.1 mg/dl; placebo, +6.0 +/- 29.4 mg/dl) in comparison with placebo. No significant changes were observed in the levels of triglycerides, high-density lipoprotein cholesterol, very low-density lipoprotein (VLDL) triglycerides, VLDL cholesterol and apolipoprotein B after valsartan treatment. No effect of valsartan was found with respect to fasting plasma glucose and glycosylated haemoglobin levels. Valsartan therapy was safe and well tolerated in our patient population. In conclusion, in addition to the marked decrease in blood pressure, valsartan significantly reduces total and LDL cholesterol levels and is neutral on glucose metabolism.
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PMID:Effect of the angiotensin II receptor antagonist valsartan on lipid profile and glucose metabolism in patients with hypertension. 1167 99

The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.
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PMID:Angiotensin II receptor blockers for the treatment of hypertension. 1182 17

Recent studies demonstrate that, treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor blockers may decrease left ventricular hypertrophy (LVH) in hypertensive patients. We wanted to assess the efficacy of valsartan on echocardiographic variables of LVH in 30 mild to moderate hypertensive patients. Valsartan was found effective in controlling hypertension, also echocardiographic indices of LVH such as interventricular septum and posterior wall thickness were reduced and left ventricular mass decreased significantly. Thus valsartan favorably influences cardiac structure in hypertensive patients.
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PMID:The efficacy of valsartan in essential hypertension and its effects on left ventricular hypertrophy. 1192 52

There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy. SHR were treated with either the angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II) AT(1)-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the effects on survival rates, cardiac and renal changes were monitored. Rats treated with valsartan, alone or in combination with enalapril, showed markedly higher survival rates (67-85%, respectively) than untreated animals (37%) or those treated with enalapril alone (55%). Valsartan at a dose which attenuated blood pressure increase led to even greater survival rates (95%). Despite these improved survival rates, at non-hypotensive doses the drugs had no effect on histological appearance, nor was kidney function improved. Plasma creatinine levels were reduced by valsartan, alone or in combination with enalapril, but proteinuria persisted with all treatments over the 12 weeks of the study. Aldosterone levels were significantly reduced by all treatments. The results suggest a beneficial role for endothelium in hypertension. Reduced renal perfusion pressure probably underlies the beneficial renal effects of high-dose valsartan.
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PMID:Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction. 1196 7

Angiotensin II receptor antagonists (AAIIs) are the most specific inhibitors of the renin-angiotensin-aldosterone system. There are two types of angiotensin II (Ang II) receptors, the AT(1) receptor, which is responsible for all the classical physiological properties of Ang II, and the AT(2) receptor, whose function in humans remains unclear. The different AAIIs used in clinical practice vary depending on their pharmacodynamic and pharmacokinetic properties, and, for some of them, depending on their metabolism in vivo into an active metabolite. AAIIs are relatively well tolerated, and, unlike angiotensin-converting enzyme inhibitors (ACEIs), do not induce cough. AAIIs are indicated in mild, moderate and severe essential hypertension, where their efficacy has been proven in many studies. The maximal antihypertensive effect is obtained in a few days or weeks, and is somewhat retarded when compared with ACEIs. Their effect is independent of age and sex, but does depend to a certain extent on ethnic origin, since Afro-American patients are less sensitive to AAIIs than Caucasians. In general, the antihypertensive and haemodynamic response to blockers of the renin-angiotensin system is potentiated in presence of a negative salt balance and attenuated in case of a positive salt balance. This means that AAII efficiency is improved by salt depletion induced by a salt-free diet or thiazide diuretics. AAIIs induce short-term improvement of haemodynamic parameters in cardiac insufficiency. Several ongoing clinical trials have been designed to compare their efficacy in cardiac insufficiency and myocardial infarction with those of reference treatments. Valsartan has been recently shown to improve morbimortality in patients with cardiac insufficiency and receiving a conventional treatment including an ACEI. It has been convincingly shown that blockade of the renin-aldosterone system by ACEIs decreases proteinuria and slows down the progression of renal insufficiency, especially in type 2 diabetic nephropathy. Recent trials have shown that AAIIs share the same properties as ACEIs in these indications. It appears that the beneficial effect of AAIIs and ACEIs is not entirely explained by the blood pressure lowering effect of these drugs. AAII administration increases renin release and Ang II production, which may overcome Ang II blockade. On this basis, the combination of an AAII and an ACEI has been proposed to achieve a maximal renin-angiotensin system blockade. Several experimental studies in animals and preliminary clinical studies all indicate that the combination of the two drugs may be more beneficial than either drug used alone in hypertension, cardiac insufficiency and post-myocardial infarction. Clinical trials are necessary to further document the putative advantages of such a combined therapy. The future of AAIIs depends on the following: progress made in the understanding of the molecular and cellular activities of angiotensin (angiotensin receptor signalling, receptor dimerisation, presence of other angiotensin receptor subtypes, role of AT(2) receptor, etc.);a comprehensive view of the role of the local renin system in various organs (local generation and effect of Ang II on cellular proliferation, fibrosis, inflammation, angiogenesis, etc.);predictability of the response to AAII treatment (genetic predisposition to AAII treatment, in conjunction with environmental factors); andresults of the ongoing clinical trials designed to assess the long-term effects of AAIIs in cardiovascular mortality and morbidity, in comparison with reference treatments.
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PMID:[Angiotensin II receptor blockers: current status and future prospects]. 1203 89

Combination of nonhypotensive doses of valsartan and enalapril markedly improved survival (+87%) compared with untreated animals (37%) in spontaneously hypertensive rats (SHRs) with endothelial dysfunction. However, the combination had no effect on kidney function, and proteinuria persisted over the 12 weeks of the study. It was hypothesized that the greater survival was due to improvement in endothelial function or coronary vasculature despite blockade of nitric oxide synthase and high blood pressure. Therefore, endothelial function was evaluated in isolated aortic ring and maximal coronary blood flow was studied in isolated perfused SHR hearts (20-24 weeks) treated with -nitro-l-arginine methyl ester (L-NAME) (50 mg/l) for 4 weeks. The animals received vehicle, valsartan 5 mg/kg/d, enalapril 1 mg/kg/d, valsartan 50 mg/kg/d, or the combination valsartan 5 mg/kg/d with enalapril 1 mg/kg/d in drinking water. Normotensive Wistar-Kyoto (WKY) rats were used as control. Blood pressure was measured by telemetry. Histopathology was performed on heart, kidney (hematoxylin-eosin), and aorta (Masson trichrome). L-NAME elevated blood pressure by 50 mm Hg after vehicle (199 +/- 5 mm Hg). Valsartan 50 mg/kg/d completely abolished this increase (150 +/- 4 mm Hg) whereas the valsartan-enalapril combination synergistically decreased blood pressure (-37 mm Hg at 162 +/- 7 mm Hg) compared with monotherapy (valsartan 5 mg/kg/d -10 mm Hg; enalapril 1 mg/kg/d -15 mm Hg). All treatments improved the histopathology, most markedly in those receiving the valsartan-enalapril combination. The severity mean grades for lesions were 2.1, 1.9, 1.7, 1.1, and 0.9 in vehicle-treated SHRs, enalapril 1 mg/kg/d, valsartan 5 mg/kg/d, valsartan 5 or 50 mg/kg/d, and the valsartan-enalapril combination, respectively, compared with 0.02 in WKY rats. Acetylcholine-induced relaxation was significantly greater in treated SHRs than after vehicle (-40% at 0.1 mmol acetylcholine) but the combination induced the maximal relaxation (-85%). The ratio of maximal tension induced by serotonin in rings with and without endothelium was 1.4 and 1.3 in vehicle and valsartan 5 mg/kg/d-treated rats whereas it did not differ from 1 in WKY rats and all other treated groups. The cardiac hypertrophy (+27%) was prevented by valsartan 50 mg/kg/d and the valsartan-enalapril combination. Coronary reserve was significantly increased by valsartan 50 mg/kg/d (+85% at 7.8 +/- 0.7 ml/min/g) and the valsartan-enalapril combination (+42% at 6.0 +/- 0.4 ml/min/g) compared with 4.2 +/- 0.5 (vehicle). This was not different of 8.8 +/- 0.5 (WKYs). Despite the maintenance of a high blood pressure, low-dose valsartan-enalapril significantly improved endothelial function and histopathology and increased coronary reserve in SHRs chronically receiving L-NAME.
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PMID:Combination of low-dose valsartan and enalapril improves endothelial dysfunction and coronary reserve in Nomega-nitro-L-arginine methyl ester-treated spontaneously hypertensive rats. 1240 88


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