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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systolic hypertension is a major risk factor for cardiovascular disease. The determinants of systolic blood pressure are peripheral resistance and arterial compliance. Arterial vasoconstriction, vascular growth and fluid retention, induced by the renin-angiotensin system directly or indirectly by enhancing sympathetic nervous system activity, are important factors in increasing peripheral resistance, decreasing arterial compliance and, consequently, elevating systolic blood pressure. Selective blockade of the angiotensin II type 1 (AT1) receptor represents a novel mechanism for interrupting the renin-angiotensin system. This provides the additional benefit of blocking angiotensin II generated by non-angiotensin-converting-enzyme pathways without altering either bradykinin metabolism or the potential beneficial effects of AT2 receptor stimulation. Eprosartan is a potent (1.4 nmol/l) AT1 receptor antagonist that inhibits angiotensin-II-induced vascular contraction in a competitive manner. Eprosartan is effective in reducing disease progression in animal models of hypertension, heart failure, renal disease and stroke. Furthermore, eprosartan causes a large increase in arterial compliance in hypertensive rats fed high-salt and high-fat diets. Eprosartan also possesses sympathoinhibitory activity as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, other angiotensin II receptor antagonists, such as losartan, used at equivalent angiotensin II blocking activity, do not appear to alter sympathetic nervous system activity. Angiotensin II receptor antagonists, such as eprosartan, that have the ability to block both the direct effects of angiotensin II and the indirect effects mediated by enhanced sympathetic neurotransmission, may represent an important advance in the treatment of elevated systolic blood pressure.
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PMID:Pharmacological mechanism of angiotensin II receptor antagonists: implications for the treatment of elevated systolic blood pressure. 1046 64

Chronic heart failure affects between 1-5% of the population and rise steeply with age. Most patients with chronic heart failure should be routinely managed with a combination of 4 types of drugs: a diuretic, an angiotensin converting enzyme inhibitors (ACE-I), beta-blocker and usually digitalis. Diuretics are essential for symptomatic treatment when fluid overload is present, and should always be administrated in combination with ACE-I if possible. ACE-I improves survival and symptoms and reduces hospitalization in patients with moderate to severe ventricular systolic dysfunction, and in the absence of fluid retention should be given first. Angiotensin II receptor antagonist could be considered in patients who not tolerate ACE-I. beta-blocking agents are recommended for treatment of patients with stable, mild, moderate and severe heart failure unless there is a contraindication. Bisoprolol, metoprolol and carvedilol have been associated with reduction in total mortality, cardiovascular mortality and sudden death. Cardiac glycosides are indicated in atrial fibrillation and any degree of symptomatic heart failure in order slow ventricular rate. Indications for antiarrhythmic drug therapy include atrial fibrillation, non-sustained or sustained ventricular tachycardia. Oral anticoagulation reduces the risk of stroke in patients with atrial fibrillation, and there is a lack of evidence to support the use of antithrombotic therapy in patients in sinus rhythm.
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PMID:[Pharmacotherapy of chronic heart failure in clinical practice]. 1551 21

The introduction of Angiotensin II receptor blockers (ARB) in 1995 was another milestone in the pharmacological management of hypertension. Due to the manifold effects on several target organs Angiotensin II is one of the most important mediator in the pathogenesis of hypertension. The blockade of the Angiotensin II receptor type 1 is a crucial cornerstone in interrupting the pathophysiological pathways in hypertension. Furthermore ARB have an excellent tolerability comparable with placebo. In the last decade large placebo-controlled trials could prove the efficiency of ARB in terms of morbidity and mortality. Patients after acute myocardial infarction and patients with chronic heart failure benefit from treatment with ARB equally compared to treatment with ACE inhibitors. Combining ARB and ACE inhibitors in patient after myocardial infarction increases the rate of adverse events without improving survival. Increase of microalbuminuria and worsening of diabetic nephropathy is reduced by ARB in patients with diabetes type 2, but an advantage over ACE inhibitors could not be documented. Hypertensive patients with electrocardiographically left ventricular hypertrophy treated with ARB seem to have an additional benefit in terms of morbidity and mortality compared to treatment with beta-blockers. In the early treatment of stroke patients treated with ARB have a lower 12-mounth mortality than patients receiving placebo. In conclusion, Angiotensin II receptor blockers are due to their well proved efficiency, the cardio- and renoprotective qualities and the excellent tolerability profile a useful therapeutic option in the management of patients with hypertension.
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PMID:[Angiotensin II receptor blockers--evidence along the cardiovascular continuum]. 1588 24

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

Clinical trials have shown that effective control of blood pressure reduces the risk of cardiovascular events in high-risk patients. For example, data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study show significant reductions in the incidence of cardiac events, stroke and all-cause mortality in patients in whom blood pressure control was achieved compared with those in whom blood pressure remained uncontrolled. Although the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) demonstrated no significant difference in cardiovascular mortality and morbidity between patients receiving diuretics, calcium channel blockers or angiotensin-converting enzyme (ACE) inhibitors, this finding might have been confounded by differences in the blood pressure reductions achieved with the three treatments. Other studies have consistently shown that newer antihypertensive agents, such as ACE inhibitors and calcium channel blockers, reduce cardiovascular events to a similar, or possibly greater, extent as older therapies, such as diuretics and beta-blockers. In particular, ACE inhibitors appear to offer additional benefits beyond blood pressure reduction in terms of reducing cardiovascular events and producing renoprotective effects. Angiotensin II receptor blockers (ARBs) have been less extensively studied, but there is evidence already that they have heart failure, stroke and renoprotective benefits. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) is currently comparing the effects of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg, alone and in combination, on cardiovascular events in high-risk patients.
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PMID:Hypertension treatment and implications of recent cardiovascular outcome trials. 1660 60

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

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.
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PMID:Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. 1734 82

The Angiotensin II receptor blockers (ARBs) have been efficacious and safe drugs for the treatment of hypertension, heart failure, diabetic nephropathy and stroke from several short and long term clinical trials. The ARBs exert their effects through selective blockade of the angiotensin II (Ang-II) subtype 1 (AT1) receptor and quite possibly through stimulation by Ang-II of the unoccupied subtype 2 (AT2) receptor. The ARBs are equipotent to other antihypertensive drugs with respect to their effect on blood pressure, heart failure or diabetic nephropathy. They appear to be superior to the other drugs with respect to their stroke protective effect. They exert their stroke protective effect by a dual action, selectively blocking the action of Ang-II on the AT1 receptors, while allowing Ang-II to stimulate the unoccupied AT2 receptors. This dual action is unique to ARBs and results in vasodilation and increase in blood flow to the ischemic zone of the brain leading to improvement and prevention of its extension. All these actions of the ARBs will be discussed in this comprehensive review.
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PMID:Clinical experience with the use of angiotensin receptor blockers in patients with cardiovascular, cerebrovascular and renal diseases. 1866 66

It is now universally accepted that antihypertensive therapy reduces cardiovascular morbidity and mortality both in young and older patients. The clinical relevance of the systolic, diastolic and pulse pressure as independent risk factors is well recognized. The reduction of cardiovascular morbidity and mortality in hypertensive patients is the main therapeutic goal. There is substantial agreement on the treatment of individual risk factors and associated clinical conditions, but the best drug therapy for systolic and diastolic hypertension and/or high pulse pressure is still controversial. The recommendations of the JNC VI are that diuretics or beta-blockers be used as first-step drug therapies. The WHO-ISH guidelines recognize calcium antagonists, ACE-inhibitors, alpha-blockers and angiotensin II receptor antagonists as first-step drug therapies together with diuretics and beta-blockers. All these drugs have a similar hypotensive potential and reduce cardiovascular risk, but with noticeable differences in tolerability and side effects. It has long been demonstrated that diuretics and beta-blockers significantly reduce the cardiovascular risk, but their side effects can be relevant. ACE-inhibitors have proved to be efficacious in hypertensive patients with chronic heart failure and diabetes. Calcium antagonists are useful in the prevention of stroke but results in patients at high risk of coronary artery disease and heart failure are controversial. Alpha-blockers have proved to be unsafe in patients with heart failure but showed beneficial effects in young patients with diastolic hypertension. Angiotensin II receptor antagonists have proved to be safe and efficient but their advantages in comparison to other drugs need to be confirmed.
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PMID:[Systolic, diastolic and pulse pressure: therapeutic options]. 1939 10


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