Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aldosterone blockade has been shown to be effective in reducing total mortality as well as hospitalization for heart failure in patients with systolic left ventricular dysfunction (SLVD) due to chronic heart failure and in patients with SLVD post acute myocardial infarction. The evidence for the effectiveness of aldosterone blockade in chronic heart failure comes from the randomized aldactone evaluation study (RALES) while that for patients post infarction from the eplerenone post acute myocardial infarction efficacy and survival study (EPHESUS). These studies suggest that mineralocorticoid receptor activation remains important despite the use of an angiotensin converting enzyme-inhibitor/angiotensin receptor blocking (ARB) agent and a beta blocker. Increasing evidence suggest that aldosterone blockade has important effects not only on the kidney but on ventricular remodeling, myocardial fibrosis, autonomic balance, fibrinolysis, oxidative stress, and activation of the NF-kappaB and AP-1 signaling pathways. The results of these studies in patients with SLVD has important implications not only for patients with chronic heart failure and post infarction but also for the therapy of patients with essential hypertension and other cardiovascular diseases.
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PMID:Effect of aldosterone blockade in patients with systolic left ventricular dysfunction: implications of the RALES and EPHESUS studies. 1513 1

Arterial stiffness has recently been recognised as an independent risk factor for cardiovascular morbidity and mortality in hypertension. Many of the complications seen with angiotensin II (Ang II) excess or hyperaldosteronism--an increased event rate, left ventricular hypertrophy, endothelial dysfunction and target organ damage--are also associated with arterial stiffness. It is possible that reduced arterial compliance may be one mechanism whereby increased activity of the renin-angiotensin-aldosterone system (RAAS) produces adverse vascular effects. Common pathophysiological processes, altered collagen turnover and increased fibrosis may underlie both arterial stiffness and RAAS-associated vascular damage. While it is recognised that patients with hyperaldosteronism have increased arterial stiffness, the role of the RAAS in modulating arterial compliance in essential hypertension and in normotensive subjects is less clear cut. There is, however, more consistent data which show that drugs that interfere with Ang II or aldosterone, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aldosterone antagonists, all reduce arterial stiffness. In many cases, this is to a greater extent than predicted from the extent of reduction in blood pressure (BP), suggesting a role for RAAS in vascular stiffness in hypertensive subjects. There is also evidence that combined ACE inhibitors (ACE-Is) and ARBs may have an additive effect in reducing stiffness. The reduction in cardiovascular mortality in end-stage renal disease patients treated with ACE-Is was preferentially seen in those who had reduced arterial stiffness. These data suggest that, in addition to regulation of vascular biology and BP, the RAAS is an important determinant of arterial stiffness in health and, more particularly, in disease.
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PMID:Arterial stiffness and the renin-angiotensin-aldosterone system. 1552 44

The aim of this study was to investigate: 1) the effects of treadmill exercise on plasma catecholamines and endothelin-1 (ET-1, a potent vasoconstrictor) levels in hypertensive patients; and 2) the impact of 1-month therapy with losartan as compared with moxonidine on catecholamine and ET-1 changes during exercise. Twenty-eight patients with essential hypertension were randomized in two groups: group A received losartan and group B received moxonidine for 1 month. Plasma catecholamines exhibited an almost 10-fold increase during exercise (p<0.00001) before treatment. Moxonidine significantly decreased catecholamine levels (p<0.05), while losartan reduction was nonsignificant (p<0.36). Plasma ET-1 increased significantly during exercise before treatment (p<0.00005). Moxonidine therapy did not affect ET-1 levels (p<0.88), while losartan resulted in a significant decrease of ET-1 levels both at baseline and during exercise (p<0.007). These findings suggest a mechanism for the reduced cardiovascular mortality noted with an angiotensin receptor blocker as compared with a sympatholytic agent.
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PMID:Different effects of losartan and moxonidine on endothelial function during sympathetic activation in essential hypertension. 1559 16

It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system, including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves. We tested this proposition in 19 patients with essential hypertension, evaluating whether the angiotensin receptor blockers (ARBs) eprosartan and losartan had identifiable antiadrenergic properties. This was done in a prospective, randomized, three-way placebo-controlled study of crossover design. Patients were randomized to 600 mg of eprosartan daily, 50 mg of losartan daily, or placebo. The treatment period was 4 wk, with 2-wk washout periods. Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature (muscle sympathetic nerve activity, MSNA) were measured with microneurography, testing whether ARBs inhibit central sympathetic outflow. In parallel, isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98 mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure, placebo corrected. Both MSNA [35 +/- 12 bursts/min (mean +/- SD) on placebo] and whole body norepinephrine spillover [366 +/- 247 ng/min] were unchanged by ARB administration, indicating that the ARBs did not materially inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing. These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class, which are known to act within the brain to inhibit sympathetic nervous outflow. We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension.
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PMID:Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension. 1628 32

Patients with essential hypertension are at increased risk of type 2 (non-insulin-dependent) diabetes. Recent large studies have been unable to delineate any superiority in one class of antihypertensive drug over another, independent of their effects in reducing blood pressure; however, in the longer term, antihypertensive agents that are able to reduce the risk of diabetes may have a theoretical advantage. To this end, the findings of several recent clinical trials have suggested that blockade of the renin-angiotensin system (RAS) may protect against the development of de-novo diabetes in 'at risk' patients. This beneficial effect appears to outweigh both the adverse metabolic effects of agents used in the control arm of these studies and the control of blood pressure achieved. Furthermore, recent evidence suggests that the RAS may have a direct role in the pathogenesis of diabetes. Angiotensin-mediated increases in oxidative stress, inflammation, and free fatty acids concentrations potentially contribute to beta-cell dysfunction in diabetes. In addition, activation of the RAS appears to potentiate the action of other pathogenic pathways, including glucotoxicity, lipotoxicity, and advanced glycation. In experimental models of type 2 diabetes, blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists also results in the improvement of islet structure and function. At least three large controlled trials are currently under way to study the utility of blockade of the RAS in the development of diabetes, including studies of combination therapy. It is hoped that these studies will demonstrate the true potential of blockade of the RAS for the prevention of diabetes.
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PMID:Preventing diabetes in patients with hypertension: one more reason to block the renin-angiotensin system. 1660 75

Laboratory studies have shown that angiotensin receptor blockers (ARBs) can affect extracellular matrix (ECM) metabolism and thereby have a beneficial effect on vascular remodeling. The aim of this study was to examine the clinical effects of the ARB candesartan cilexetil on serum markers of synthesis and degradation of ECM, as well as their relation to changes in arterial stiffness in hypertensive patients. Twenty-three patients with essential hypertension were recruited for this study. Markers related to ECM synthesis and degradation (procollagen type 1 propeptide [PIP], procollagen type III propeptide [PIIIP], matrix metalloproteinase-3 [MMP-3, stromelysin-1], tissue inhibitor of matrix metalloproteinases [TIMP-1], and hyaluronic acid [HA]) were examined both before and after one year of treatment with candesartan. Pulse-wave velocity [PWV] and ankle-brachial pressure index [ABI] were measured two months (i.e., after achieving blood pressure reduction) and one year after the initiation of therapy. PWV values after one year of treatment with ARB were significantly decreased compared to previous values, whereas ABI values were unchanged. Treatment with ARB was also associated with a significant decrease in serum PIIIP values and an increase in serum stromelysin-1, whereas changes in PIP, TIMP-1, and HA did not achieve statistical significance. A significant relationship was found between the changes in PWV and the changes in stromelysin-1 levels after correction for blood pressure and heart rate (p = 0.02). These results suggest that the treatment for just one year with ARB results in significant changes in markers of ECM metabolism as well as PWV. These effects on ECM metabolism could have a beneficial effect in decreasing vascular pathology in patients with essential hypertension.
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PMID:Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension. 1682 Mar 47

Hypertension is a cardiovascular risk factor commonly associated with insulin resistance, the metabolic syndrome, and type 2 diabetes mellitus. Recent in vitro data indicate that certain angiotensin receptor antagonists, for example, telmisartan, activate peroxisome proliferator-activated receptor gamma (PPAR-gamma) and increase adiponectin protein content in adipocytes. By this means, they may improve insulin sensitivity in vivo. To investigate the effect of antihypertensive treatment on insulin sensitivity and fasting adiponectin serum levels, 37 nondiabetic patients with essential hypertension were randomized to receive telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks in a prospective, parallel group study. Fasting serum glucose, insulin, and adiponectin were evaluated before, 3 weeks (low dose), and 6 weeks (high dose) after initiation of treatment. Furthermore, the effect of telmisartan on PPAR-gamma receptor activity was investigated in vitro using a PPAR-gamma reporter gene assay. As reported previously, telmisartan significantly enhanced PPAR-gamma receptor activity in vitro. At baseline, a positive correlation between insulin serum levels and body mass index of investigated subjects was observed, whereas body mass index and serum adiponectin levels were negatively associated. High-dose treatment with telmisartan but not with nisoldipine reduced serum insulin levels as well as the homeostasis model assessment of insulin resistance, but did not affect serum adiponectin levels. In conclusion, in our study cohort of nondiabetic patients with essential hypertension, telmisartan improved insulin sensitivity by mechanisms apparently not involving adiponectin induction. Future studies will demonstrate whether these telmisartan-induced effects may contribute to a blood pressure-independent reduction in cardiovascular morbidity.
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PMID:Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension. 1691 33

Hypertension is a well documented risk factor for cardiovascular disease (CVD) and substantially contributes to the global burden of disease. Different drug options exist for combination therapy as part of an overall control of risk factors in order to decrease the absolute risk of CVD. Several guidelines in recent years have tried to set up recommendations to increase the proportion of subjects in acceptable BP control from high-risk groups. Some conventional drugs are still very important in modern hypertension treatment, e.g. low-dose thiazide diuretics. However, newer compounds have added to the list of useful agents to be used as monotherapy or in combination therapy for improved target organ protection, e.g. the calcium channel antagonists and ACE inhibitors. The role of beta-adrenoceptor antagonists (beta-blockers) has changed somewhat as a result of critical comments from recent meta-analyses. Currently, therefore, beta-blockers are recommended less often for primary prevention and monotherapy, but should still be used for secondary prevention, combination therapy, and for symptom relief. Finally, the new angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) are still rather expensive, but have been increasingly documented in clinical trials for patients with essential hypertension. One controversial aspect is whether ARBs are better, worse, or equal to standard therapy with an ACE inhibitor for cardiovascular protection. BP remains poorly controlled in a large number of hypertensive patients and there is a greater need to control all relevant CVD risk factors in such patients. Therefore, different drugs are needed in order to be used in evidence-based synergistic and cost-effective drug combinations.
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PMID:Optimizing the pharmacologic treatment of hypertension: BP control and target organ protection. 1708 63

Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.
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PMID:Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. 1709 Jun 78

It is known that the angiotensin receptor blockers (ARBs) have organ protective effects in patients with heart failure or renal impairment. Several studies have revealed that the ARB telmisartan has an organ protective effect, but there have been few studies directly comparing the effects of telmisartan and calcium antagonists, since most clinical studies on telmisartan have been conducted in treated patients or patients on combination therapy. The present study was conducted to compare the renal and vascular protective effects of telmisartan monotherapy and calcium antagonist monotherapy in untreated hypertensive patients. Forty-three patients with untreated essential hypertension were randomized to receive amlodipine (n=22) or telmisartan (n=21), which were respectively administered at doses of 5 mg and 40 mg once daily in the morning for 24 weeks. The patients were examined before and after treatment to assess changes of renal function, flow-mediated dilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (baPWV; a parameter of arteriosclerosis). Before treatment, there were no significant differences in these parameters between groups. The decreases of urinary albumin excretion and baPWV, and the increase of flow-mediated dilation were significantly greater in the telmisartan group than the amlodipine group, while the antihypertensive effects were not significantly different between the two groups. In conclusion, these results suggest that telmisartan is more effective at protecting renal function and vascular endothelial function, and at improving arteriosclerosis than the calcium channel blocker in patients with essential hypertension.
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PMID:Renal and vascular protective effects of telmisartan in patients with essential hypertension. 1713 11


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