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

Aldosterone is one the representative cardiovascular hormones involved in the blood pressure and body-fluid homeostasis. Elevation of aldosterone leads to systemic hypertension through its action on the mineralocorticoid receptor (MR) in the kidney. More recent studies demonstrated that aldosterone may produce target organ damage through its direct actions on the non-epithelial MR of the heart in addition to its systemic effects. Clinical experience in primary aldosteronism supports the concept that aldosterone is a risk factor of cardiovascular complications, since concentric type of cardiac hypertrophy is most common in primary aldosteronism among various types of endocrine hypertension. Clinical mega-trial in congestive heart failure (RALES study, EPHESUS study) demonstrated blocking angiotensin II action is not sufficient for cardioprotection unless aldosterone action is equally blocked. An important phenomenon related to this issue is the aldosterone breakthrough which implies a reelevation of plasma aldosterone during chronic administration of ACE inhibitors and Angiotensin receptor antagonists. Normal level of aldosterone could still be a risk factor. Combination of ACE inhibitor or ARB with aldosterone antagonist could result in a better cardioprotection in cardiovascular diseases. Although spironolactone has been the only one aldosterone antagonist, a new antagonist eplerenone has been developed. Eplerenone is specific to MR and is practically devoid of the major side effect gynecomastia of spironolactone. Another topic of aldosterone is its very quick cardiovascular effect presumably via a non-genomic action. All these recent findings support that this adrenocortical steroid hormone is as important as angiotensin II. Determining aldosterone levels is therefore much morel important than before in the diagnosis and treatment of cardiovascular diseases.
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PMID:[Aldosterone]. 1547 26

Hypertension has long been considered a homodynamic disorder. In recent years, because of the introduction of innovative methods of measurement of pulse wave velocity (PWV), it is now possible to obtain an assessment of physiological role of the large arteries, thereby providing an index of arterial stiffening in hypertension. Now, brachial-ankle pulse wave velocity (baPWV) is a noninvasive and simple method of measuring arterial stiffness. We evaluated that baPWV is well correlated with age, blood pressure and many atherosclerotic risk factors. Clinical studies have shown that baPWV is improved by decreases in blood pressure and ARB. The ARB yields the largest reduction in baPWV followed by calcium channel blocker (CCB). Although ARB achieved the largest reduction in baPWV, the decreases were not only associated with the blood pressure but also with the endothelium function.
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PMID:[Anti-hypertensive drugs associated with the improvement of pulse wave velocity]. 1559 7

We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide. Fixed combination ARB/hydrochlorothiazide agents make sense as initial therapy for patients in whom BP is >20/10 mm Hg above goal.
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PMID:Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide. 1563 34

Large, placebo-controlled RCTs that involve only diabetic patients who have hypertension have not been performed. Subgroup analyses of hyper-tension control from several recent RCTs un-equivocally demonstrated greater benefit in diabetic populations (see Table 3) with ACE inhibitors, TDs, and CCBs. Treatment with fBs(atenolol) also was beneficial in diabetic patients who had hypertension in the actively-controlled UKPDS. The results of three RCTs support intensive BP control in diabetic patients (see Table 4). In these trials, diabetic patients gained more benefit than nondiabetic patients. Such an effect is consistent with the fact that diabetics are at higher risk for CV events. Although there are limited data from RCTs with head-to-head comparison of newer agents (eg,ACE inhibitors, ARBs, CCBs) to show that these drugs are better than diuretics and betaBs in reducing CV events by treating hypertension in the diabetic population, the available data support ACE inhibitors (and ARBs if ACE inhibitors are not tolerated) as an initial drug of choice in diabetic,hypertensive patients (see Table 5). Most diabetic patients require three or four drugs to control their BP to target range; as such, it is not necessary to justify the choice of any single class of drug. Tight BP control is cost-effective and is more rewarding than hyperglycemic control in diabetic,hypertensive patients. The optimal goal in diabetics should be to achieve BP that is less than 130/80 mm Hg. Appropriate action should be taken if BP is greater than 140/85 mm Hg. In subjects who have diabetes and renal insufficiency,the BP should be decreased to less than 125/75 mm Hg to delay the progression of renal failure. Limited data suggest that an ACE inhibitor or an ARB is the agent of choice, especially in patients who have proteinuria or renal insufficiency. betaBs can be the first-line agent in diabetics who have CAD. TDs and CCBs are the second line drugs.AAAs should be avoided. Most hypertensive patients require more than one agent to adequately control their BP. There is no evidence to support one combination regimen over the others, nevertheless, the combination of an ACE inhibitor with a TD or a fPB may be more beneficial and cost effective than other combinations in the diabetic population. Large outcome studies that compare different combination therapies in hypertensive,diabetic patients are needed.
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PMID:Diabetes and hypertension, the deadly duet: importance, therapeutic strategy, and selection of drug therapy. 1569 43

High blood pressure raises the risks of vascular dementia and cognitive dysfunction in older adults, by acting on the cerebral vasculature and directly on the brain itself. Clinical trials and observational studies have shown that treating hypertension to target (<140/90 mm Hg) not only lessens morbidity and mortality, but also improves quality of life and preserves cognitive function. Yet, only 34% of hypertensive Americans currently have their hypertension under control, despite widespread treatment. Although single drug therapy is effective in treating hypertension, most patients will require combination drug treatment. Combination therapy--typically a diuretic with an ACE inhibitor, an ARB, or a beta blocker--is appropriate for treatment of older patients, is well tolerated, and can effectively preserve cognitive function.
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PMID:Hypertension and cognitive function. Blood pressure regulation and cognitive function: a review of the literature. 1570 Sep 45

The present study explored the possibility that estrogen enhances the inhibitory effect of an angiotensin II type-1 (AT1) receptor blocker (ARB), olmesartan, on atherosclerosis, focusing on oxidative stress using apolipoprotein E knockout mice (ApoEKO). After 6 weeks on a high-cholesterol diet, marked atherosclerotic lesion formation with an increase in oxidative stress, such as superoxide production, NAD(P)H oxidase activity and expression of p47phox mRNA and rac-1 mRNA, were observed in the proximal aorta in both male and female ApoEKO mice, whereas these changes were less marked in female mice. Ovariectomy enhanced these parameters, the changes of which were reversed by 17beta-estradiol (80 microg/kg per day) replacement. Treatment with olmesartan (3 mg/kg per day) significantly inhibited oxidative stress and atherosclerosis, whereas its inhibitory effects were more marked in female than in male or ovariectomized mice. Smaller doses of olmesartan (0.5 mg/kg per day) or 17beta-estradiol (20 microg/kg per day) did not influence atherosclerosis and oxidative stress in ovariectomized mice, whereas co-administration of olmesartan and 17beta-estradiol at these doses attenuated these parameters. An angiotensin-converting enzyme (ACE) inhibitor, temocapril, also inhibited atherosclerotic changes similarly to olmesartan. Moreover, angiotensin II-mediated activation of NAD(P)H oxidase in cultured vascular smooth muscle cells was attenuated by 17beta-estradiol. These results indicate that estrogen and an ARB synergistically attenuate atherosclerosis at least partly via inhibition of oxidative stress.
Hypertension 2005 Apr
PMID:Inhibitory effects of AT1 receptor blocker, olmesartan, and estrogen on atherosclerosis via anti-oxidative stress. 1572 67

The present study was undertaken to examine the effects of a calcium channel blocker, azelnidipine (1 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, temocapril (10 mg/kg/day), an angiotensin II type 1 (AT1) receptor blocker (ARB), olmesartan (5 mg/kg/day), and their combination on Dahl salt-sensitive rats (DS rats) developing heart failure with preserved systolic function. DS rats were fed a high-salt diet (8% NaCl) from 7 weeks of age and progressively developed hypertension. Although monotherapy with azelnidipine lowered the blood pressure of DS rats to a greater extent than monotherapy with temocapril or olmesartan, the three drugs had similar effects on cardiac hypertrophy, cardiac fibrosis, the expressions of brain natriuretic peptide, transforming growth factor-beta1, collagen I, collagen III and monocyte chemoattractant protein-1 mRNA (as estimated by Northern blot analysis), and cardiac diastolic dysfunction (as estimated by echocardiography). These results show that ACE and AT1 receptor, as well as hypertension, are involved in the development of heart failure with preserved systolic function in DS rats. The combination of azelnidipine with olmesartan or temocapril produced no additive hypotensive effect in DS rats and no additive effect on cardiac hypertrophy or gene expressions. However, the combination therapy prolonged the survival rate of DS rats more than azelnidipine (p <0.01) or temocapril alone (p <0.05), and this additive beneficial effect by the combination therapy was associated with a greater reduction of cardiac fibrosis, urinary albumin excretion and serum creatinine. Our results thus showed that the combination of a calcium channel blocker with an ARB or an ACE inhibitor had additive preventive effects on a rat model of hypertensive heart failure with preserved systolic function. Thus, combination therapy with these agents seems to be a useful therapeutic strategy for the prevention of hypertensive heart failure.
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PMID:Additive beneficial effects of the combination of a calcium channel blocker and an angiotensin blocker on a hypertensive rat-heart failure model. 1578 13

There is a growing body of evidence that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Indeed, large clinical trials have demonstrated a substantial benefit of the blockade of this system for cardiovascular-organ protection. Although several types of angiotensin II type 1 (AT1) receptor blockers (ARBs) are commercially available for the treatment of patients with hypertension, comparisons of the binding affinity to AT1 receptor among them remain to be elucidated. In this study, we examined the dissociation rate of several ARBs from AT1 receptor in vitro. Angiotensin II time-dependently dissociated telmisartan, olmesartan, candesartan, valsartan, losartan and an active metabolite of losartan, EXP3174, from membrane components containing human AT1 receptor The dissociation rate constant of each ARB was 0.003248, 0.004171, 0.005203, 0.009946, 0.01027 and 0.008561 min(-1), with corresponding half-lives of 213, 166, 133, 70, 67 and 81 min, respectively. These results demonstrate that telmisartan has the strongest binding affinity to AT1 receptor among various ARBs examined herein. The rank order of affinity was telmisartan > olmesartan > candesartan > EXP3174 > or = valsartan > or = losartan. The present findings suggest that telmisartan (Micardis) may have long-lasting blood pressure-lowering effects and superior cardioprotective properties in patients with hypertension due to its strongest AT1 receptor antagonistic ability.
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PMID:Telmisartan has the strongest binding affinity to angiotensin II type 1 receptor: comparison with other angiotensin II type 1 receptor blockers. 1586 75

This study was performed to determine whether augmented intrarenal angiotensinogen may contribute to the enhanced renal angiotensin II (Ang II) and associated tissue injury in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were maintained on a normal diet and killed at either 7 or 14 wk of age. Two groups of SHR received either an Ang II type 1 receptor blocker (ARB; olmesartan, 5 mg/d) or a triple therapy (hydralazine 7.5 mg/d, reserpine 0.15 mg/d, and hydrochlorothiazide 3 mg/d [HRH]) during weeks 7 through 14. Systolic BP and renal Ang II were significantly increased in SHR-14 (n = 8) compared with WKY-7, WKY-14, and SHR-7 (n = 8 each), and ARB treatment prevented these increases (n = 8). However, whereas HRH treatment prevented the development of hypertension in SHR, this combination therapy failed to decrease renal Ang II (n = 8). With the use of urine samples or fixed renal sections, renal injuries in rats were quantified in a semiautomated manner by the following six parameters: (1) urinary excretion rate of total protein, (2) glomerular sclerosis, (3) interstitial expansion, (4) and (5) numbers of monocytes/macrophages in interstitium or glomeruli, and (6) arterial proliferation. Angiotensinogen mRNA and protein levels in kidney cortex, measured by real-time reverse transcriptase-PCR and Western blot analysis, respectively, and all six parameters of renal damage were changed in parallel, and ARB treatment also prevented these increases. However, HRH treatment failed to prevent these increases. These results indicate that SHR have enhanced intrarenal angiotensinogen production that contributes to increased Ang II levels leading to the development of hypertension and renal injury in this strain.
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PMID:Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats. 1588 67

Angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics have an accepted place in the management of hypertension. Most patients require combination therapy with two or more drugs to adequately control blood pressure to targets recommended by European and international guidelines. ARBs and the thiazide diuretic hydrochlorothiazide have complementary modes of action. Fixed-dose combinations of an ARB and low-dose hydrochlorothiazide provide a convenient and effective treatment option for patients who do not achieve blood pressure targets on monotherapy, without compromising the placebo-like tolerability of ARBs. In Europe, fixed-dose combinations with hydrochlorothiazide currently are available for the ARBs candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan. Recently, a number of studies have focused on the use of ARBs in monotherapy and in combination therapy, in conditions including congestive heart failure, post-myocardial infarction management, hypertension with cardiovascular risk factors, and diabetic and non-diabetic nephropathy. Evidence from these studies suggests a beneficial role beyond the antihypertensive effect of these therapies in providing protection against cardiovascular, renovascular, and cerebrovascular events.
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PMID:Angiotensin II receptor antagonists alone and combined with hydrochlorothiazide: potential benefits beyond the antihypertensive effect. 1590 Dec 5


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