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

From a patient's perspective, stroke is the most devastating form of cardiovascular disease, representing the number one cause of permanent disability in the United States. Treatment of hypertension significantly reduces the risk of stroke; however, it is unclear whether all antihypertensive agents are equivalent in this regard. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the risk of cardiovascular events, including stroke. Although attenuation of the renin-angiotensin system (RAS) is often credited with the blood pressure-independent effects of this class of agents, this hypothesis has not been confirmed with regard to the end point of stroke. In fact, drugs that activate the RAS, such as diuretics and dihydropyridine calcium channel blockers, are as effective or superior to ACE inhibitors for stroke prevention. Angiotensin II receptor blockers (ARBs) selectively block the angiotensin II subtype I receptor, which results in a reflexive increase in levels of angiotensin II and unopposed activation of angiotensin II subtype 2 receptors. Clinical trials comparing ARBs with active controls have reported significant reductions in stroke in ARB-treated patients. Data on ARBs and other drugs that activate the RAS (diuretics and dihydropyridine calcium channel blockers) support a potential role for the RAS in protecting against stroke. Ongoing trials with ARBs are evaluating stroke as a primary end point, and results should help to further elucidate the role of ARBs in this disease. Until then, it is prudent to treat hypertension with an agent or combination of agents that are likely to result in a rapid and sustained reduction in blood pressure, taking into consideration patient characteristics, comorbidities, tolerability, and cost.
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PMID:Can the renin-angiotensin system protect against stroke? A focus on angiotensin II receptor blockers. 1597 15

Angiotensin II receptor blockers (ARBs) may produce a number of molecule-specific effects that appear to be independent of interaction with the angiotensin II type 1 (AT1)-receptor. These include antagonism of the thromboxane A2 receptor, inhibition of platelet aggregation, induction of peroxisome proliferator- activated receptor gamma (PPARgamma) activity, and reduction of serum uric acid levels. However, definitive evidence is lacking that these molecule-specific effects give rise to a therapeutic advantage of one ARB over another. Currently, the possibility of a link between a molecule-specific effect of an ARB and an improvement in clinical outcomes is best illustrated by a reduction in serum uric acid levels with losartan. Data from Losartan Intervention For Endpoint reduction in hypertension (LIFE) study suggest a treatment-induced decrease in serum uric acid may contribute to the treatment benefit of a losartan-based versus atenolol-based therapy on the composite endpoint (death, myocardial infarction, or stroke). This finding should prompt further studies to investigate the long-term cardioprotective benefits issue of reducing hyperuricaemia in hypertensive patients.
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PMID:Molecular-specific effects of angiotensin II antagonists: clinical relevance to treating hypertension? 1608 47

Angiotensin II, the major effector molecule produced from the renin-angiotensin-aldosterone axis, is a vasoconstrictor contributing to hypertension. Evidence indicates, however, that angiotensin II also is a potent proinflammatory mediator with growth and remodeling effects. In vitro and in vivo studies have shown that angiotensin II blockade significantly reduces concentrations of proinflammatory mediators and oxidative stress products in numerous inflammatory models. Interruption of angiotensin II activity with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been beneficial for patients with inflammatory diseases. Much of this benefit occurs independent of the antihypertensive effect of angiotensin II interruption, suggesting a distinctive protective mechanism. Angiotensin II receptor blockers may represent a novel class of antiinflammatory drugs with indications far beyond cardiovascular diseases.
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PMID:Protective effects of angiotensin II interruption: evidence for antiinflammatory actions. 1616 95

(1) Some angiotensin-converting-enzyme inhibitors (ACE inhibitors) reduce mortality in patients with heart failure (captopril, enalapril, ramipril and trandolapril), and in patients with recent myocardial infarction and heart failure or marked left ventricular dysfunction (captopril, ramipril and trandolapril). (2) Angiotensin II receptor antagonists, otherwise known as angiotensin receptor blockers, have haemodynamic effects similar to ACE inhibitors, but differ in their mechanism of action and certain adverse effects. (3) Five clinical trials have evaluated angiotensin II receptor antagonists (candesartan, losartan and valsartan) in terms of their effect on mortality and on the risk of clinical deterioration in patients with symptomatic heart failure, but without severe renal failure, hyperkalemia or hypotension. In these trials, candesartan and valsartan were used at much higher doses than those recommended for the treatment of arterial hypertension. (4) In patients with heart failure who were not taking an angiotensin II receptor antagonist or an ACE inhibitor at enrollment, no significant difference was found between losartan and captopril in terms of mortality or the risk of clinical deterioration. (5) In patients with heart failure who had stopped taking an ACE inhibitor because of adverse effects, candesartan had no effect on mortality as compared with placebo, but it did reduce the risk of clinical deterioration (3 fewer hospitalisations per year per 100 patients). However, candesartan was associated with adverse effects such as renal failure and hyperkalemia, especially in patients who had experienced these same adverse effects while taking an ACE inhibitor. (6) In patients with heart failure who were already taking an ACE inhibitor, adjunctive candesartan or valsartan treatment did not influence mortality in comparison to the addition of a placebo. Adding candesartan or valsartan reduced the risk of hospitalisation (between 1 and 3 fewer hospitalisations per year per 100 patients), but increased the risk of renal failure and hyperkalemia. (7) In patients with heart failure and incapacitating dyspnea despite ACE inhibitor + diuretic combination therapy, there are no trials comparing the addition of an angiotensin II receptor antagonist versus spironolactone. Adjunctive spironolactone therapy prevents 5 to 6 deaths per year per 100 patients in this setting. (8) In patients with heart failure who do not have markedly altered cardiac contractility, candesartan appears to have no clinical advantages over placebo. (9) In some of these trials, mortality was higher with angiotensin II receptor antagonist therapy than with placebo among patients who were already taking a betablocker. (10) Two trials have compared an angiotensin II receptor antagonist with an ACE inhibitor in patients with recent myocardial infarction who had heart failure or an altered left ventricular ejection fraction, but who did not have hypotension or severe renal failure. However, there are no placebo-controlled randomised trials assessing the effects of angiotensin II receptor antagonists on mortality. (11) In patients with recent myocardial infarction, these trials showed no difference in mortality between angiotensin II receptor antagonist treatment (losartan or valsartan) and captopril. They did not rule out the possibility that these angiotensin II receptor antagonists are moderately less effective than captopril. Adding valsartan to ongoing captopril therapy did not reduce mortality or morbidity as compared with placebo, but did increase the risk of adverse effects. (12) Overall, these trials confirm the advantage of angiotensin II receptor antagonists over ACE inhibitors with respect to some adverse effects (cough, skin rash, etc.). However, the two drug classes share certain serious adverse effects such as hyperkalemia, renal failure and hypotension. In one trial, angioedema was less frequent with angiotensin II receptor antagonist therapy (one less case per 500 patients).
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PMID:Angiotensin II receptor antagonists and heart failure: angiotensin-converting-enzyme inhibitors remain the first-line option. 1628 75

Angiotensin II receptor density in the brain is elevated when dietary salt intake is raised or in the state of hypertension. The aim of this study was to evaluate whether the angiotensin II modulation of the baroreceptor control of renal sympathetic nerve activity was altered under these conditions. Wistar rats, fed either a regular (0.25% w/w sodium) or high-salt diet (3.1% w/w sodium), or stroke-prone spontaneously hypertensive rats (SHRSPs) were implanted with cannulae in the carotid artery, jugular vein and the cerebroventricle and with recording electrodes on the renal sympathetic nerves. Three days later, baroreceptor gain curves were generated for renal sympathetic nerve activity and heart rate before and following intracerebroventricular (i.c.v.) administration of losartan (15 mug) to block angiotensin AT1 receptors. The rats fed a regular diet had a mean blood pressure of 116 +/- 3 mmHg and heart rate of 467 +/- 25 beats min(-1), which remained unchanged after the i.c.v. administration of losartan. The sensitivity or curvature coefficient of the baroreceptor curve for renal sympathetic nerve activity was increased by 36% (P < 0.05) following losartan. In the rats fed a high-salt diet, all cardiovascular variables and the losartan-induced increase in the baroreceptor curvature coefficient for renal sympathetic nerve activity (29%) were similar to values in rats on the regular sodium diet. The heart rate baroreceptor curvature coefficient was not altered in either the rats fed a regular or a high-salt diet. The slope of the renal sympathetic nerve activity baroreflex gain curve in the SHRSPs was less and the increase following administration of losartan (54%) was greater than in the Wistar rats. These data indicate that in the conscious state, the tonic inhibitory action of brain angiotensin II on the baroreflex regulation of renal sympathetic nerve activity was unaffected by raised dietary sodium, but its role was enhanced in the SHRSPs.
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PMID:The contribution of brain angiotensin II to the baroreflex regulation of renal sympathetic nerve activity in conscious normotensive and hypertensive rats. 1669 Jul 14

The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin II receptor blockers (ARBs) inhibit angiotensin II type 1 receptors and large clinical trials have shown that they are effective in many cardiovascular diseases including hypertension, heart failure, myocardial infarction and diabetic nephropathy. They lower blood pressure effectively, are very well tolerated and can be used as monotherapy or in combination with other drug classes for the treatment of hypertension. ARBs are particularly suitable for hypertensive patients with co-morbidities such as diabetes, microalbuminuria, proteinuria, left ventricular hypertrophy and heart failure. Unlike angiotensin-converting enzyme inhibitors, ARBs do not cause persistent dry cough. For patients in whom angiotensin-converting enzyme inhibitors are indicated but not tolerated, an ARB should be considered. Periodic monitoring of renal function and electrolytes is required in patients treated with an ARB.
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PMID:Therapeutic potential of angiotensin receptor blockers in hypertension. 1673 15

Lowering blood pressure is the most effective treatment method to ensure a reduction in the total risk for cardiovascular morbidity and mortality. The renin-angiotensin system plays an important role in volume homeostasis and blood pressure regulation and is a target for several groups of pharmaceutical agents. Angiotensin II receptor blockers represent the newest class of antihypertensive compounds. They prevent the binding of angiotensin II to the subtype 1 receptor (AT(1)), which is believed to mediate most of the physiological actions relevant to the regulation of blood pressure. Telmisartan, a widely used AT(1) receptor antagonist, is a highly selective compound with high potency, a long duration of action and a tolerability profile similar to placebo. Numerous randomized clinical trials and community-based studies have demonstrated that oral telmisartan and combinations of telmisartan with hydrochlorothiazide are at least as effective in lowering blood pressure as all other hypertensive medications. This has been demonstrated in different populations of adult patients with mild-to-moderate essential hypertension, including patients with coexisting Type 2 diabetes, metabolic syndrome or renal impairment. Several large-scale, long-term, clinical endpoint studies are in progress to assess the beneficial effects of telmisartan on hypertension-related end-organ damage in patients at high risk of renal, cardiac and vascular damage whose blood pressure is well controlled. The most recent data from clinical trials and latest research regarding telmisartan will be reviewed in this article.
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PMID:Effective treatment of hypertension by AT(1) receptor antagonism: the past and future of telmisartan. 1708 Oct 84

Although treatments of hypertension have significantly decreased morbidity and mortality from cerebrovascular disease, the associated reductions in coronary artery disease have been very disappointing. Hypertension is a complex inherited syndrome of cardiovascular risk factors, all of which contribute to the development of heart disease. Angiotensin II receptor blockers (ARBs), such as the highly selective ARB valsartan, provide an alternative treatment strategy to address the multiple issues in coronary artery disease. These agents are well-tolerated and have a once-daily regimen that improves compliance. They bring multiple cardiovascular benefits beyond blood pressure (BP) control, such as renoprotection and cardiovascular growth reduction.
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PMID:Hypertension and its management: a problem in need of new treatment strategies. 1719 12

Obesity, hypertension, dyslipidemia and glucose intolerance cluster in the insulin resistance syndrome. Angiotensin II receptor blockers (ARB) are able to reduce insulin resistance. Furthermore, among ARB, telmisartan displays the property of stimulating PPARgamma. The aim of the study was to examine if and to what extent treatment with irbesartan and telmisartan induces variations in metabolic parameters in insulin resistant, hypertensive subjects. Forty-six non diabetic, obese, insulin-resistant, hypertensive patients took part in the study. They were divided into 2 groups. Group A (23) was submitted to irbesartan 150 mg/day, Group B (23) to telmisartan 80 mg/day for 6 months. Adiponectin, glucose, cholesterol, triglycerides, free fatty acids (FFA), steady-state plasma insulin and glucose (SSPG), 24-hBP were determined at the beginning and at the end of the study. Both irbesartan or telmisartan reduced blood pressure and ameliorated the insulin sensitivity, with increased adiponectin values; in Group B, the amelioration of metabolic parameters was greater than in Group A and the reduction of blood pressure was related with variation of adiponectin levels. Data obtained showed that the antihypertensive action of telmisartan and irbesartan is associated with the amelioration of the metabolic picture. The greater impact on the improvement of the metabolic profile showed by telmisartan and the inverse correlation between adiponectin levels and blood pressure may be partly due to the action as partial PPARgamma agonist displayed by telmisartan.
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PMID:The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients. 1725 91

Genetic studies of human and experimental hypertension provide a means to identify key pathways that predispose individuals to increased blood pressure and associated risk factors for cardiovascular and metabolic diseases. The pathways so identified can then serve as targets for therapeutic intervention. This article discusses genetic studies in animal models of hypertension in which specific genes have been identified that regulate blood pressure and biochemical features of the metabolic syndrome. Consistent with studies in humans with monogenic disorders of blood pressure regulation, studies in rat models have demonstrated that naturally occurring genetic variation in pathways regulating sodium chloride transport can contribute to inherited variation in blood pressure. Such studies have also indicated that naturally occurring variation in genes, such as Cd36, that regulate fatty acid metabolism and ectopic accumulation of fat and fat metabolites can influence both biochemical and hemodynamic features of the metabolic syndrome and mediate the antidiabetic effects of drugs that activate the peroxisome proliferator-activated receptor-gamma. Angiotensin II receptor blockers with the ability to selectively modulate activity of peroxisome proliferator-activated receptor-gamma and expression of genes in these fat metabolism pathways may represent useful prototypes for a new class of transcription modulating drugs aimed at treating patients with hypertension and the metabolic syndrome.
Hypertension 2007 May
PMID:Molecular genetics of experimental hypertension and the metabolic syndrome: from gene pathways to new therapies. 1733 35


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