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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

Selective blockade of the angiotensin II AT1 receptor represents a novel mechanism for interrupting the renin-angiotensin system without altering the potential benefits of AT2 receptor stimulation. This selective inhibition produces none of the disadvantages associated with reduced bradykinin metabolism and angiotensin II generated by non-angiotensin-converting enzyme pathways. Eprosartan is a potent (1.4 nmol/L) AT1 receptor antagonist that competitively blocks angiotensin II-induced vascular contraction. In various animal models of disease, including hypertension and stroke, eprosartan is effective in reducing disease progression. Eprosartan also has 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, some of the other angiotensin II receptor antagonists, such as losartan, at equivalent angiotensin II blocking doses, have no effect on sympathetic nervous system activity. Because eprosartan can inhibit both the direct effects of angiotensin II as well as the indirect effects that are mediated by enhanced sympathetic neurotransmission, this may represent an important advance in the treatment of elevated systolic blood pressure.
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PMID:Pharmacology of eprosartan, an angiotensin II receptor antagonist: exploring hypotheses from clinical data. 1046 20

The effects of the angiotensin type 1 (AT(1)) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 +/- 9 versus 284 +/- 8 mm Hg), renal expression of transforming growth factor-beta mRNA (1.5 +/- 0.2 versus 5.4 +/- 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 +/- 1.4 versus 31.4 +/- 10.7), fibronectin (2.2 +/- 0.6 versus 8.2 +/- 2.2), collagen I-alpha 1 (5.6 +/- 2.0 versus 23.8 +/- 7.3), and collagen III (2.7 +/- 0.9 versus 7.6 +/- 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [=1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 +/- 0.1 versus 1.9 +/- 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 +/- 2 versus 127 +/- 13 mg/day) and histological evidence of active renal damage (5 +/- 2 versus 195 +/- 6) and renal fibrosis (5.9 +/- 0.7 versus 16.4 +/- 1.9) in vehicle- versus eprosartan-treated rats, respectively. Our results demonstrated that AT(1) receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-beta1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP.
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PMID:The angiotensin type 1 receptor antagonist, eprosartan, attenuates the progression of renal disease in spontaneously hypertensive stroke-prone rats with accelerated hypertension. 1190 53

Antihypertensive agents are proven to reduce the cardiovascular risk of stroke, coronary heart disease and cardiac failure. The ideal antihypertensive agent should control all grades of hypertension and have a placebo-like side effect profile. Angiotensin II (AII) receptor antagonists are a relatively new class of antihypertensive agent that block AII Type 1 (AT(1)) receptors, and reduce the pressor effects of AII in the vasculature. By this mechanism, they induce similar pharmacological effects compared with angiotensin-converting enzyme (ACE) inhibitors, resulting in a lowering of blood pressure. However, AII receptor blockers differ from ACE inhibitors with respect to side effects, and induce less cough, a side effect which may be related to bradykinin or other mediators such as substance P. Within the class of AII blockers, eprosartan differs from other currently available agents in terms of chemical structure, as it is a non-biphenyl, non-tetrazole, non-peptide antagonist with a dual pharmacological mode of action. Eprosartan acts at vascular AT(1) receptors (postsynaptically) and at presynaptic AT(1) receptors, where it inhibits sympathetically stimulated noradrenaline release. Its lack of metabolism by cytochrome P450 enzymes confers a low potential for metabolic drug interactions and may be of importance when treating elderly patients and those on multiple drugs. In clinical trials, eprosartan has been demonstrated to be at least as effective in reducing blood pressure as the ACE inhibitor enalapril, and has significantly lower side effects. Eprosartan is safe, effective and well-tolerated in long-term treatment, either as a monotherapy or in combination with other antihypertensive drugs such as hydrochlorothiazide.
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PMID:Eprosartan for the treatment of hypertension. 1251 47

Twenty patients with stroke of hemisphere localization developed as a result of arterial hypertension were treated with eprosartan mesilat. An estimation of the drug efficacy was conducted in comparison with other hypotensive medicines (control group). Eprosartan was used in dosage 600 mg daily. The study was carried out during 12 months, along with a monitoring of the most relevant hemodynamic indices, evaluation of somatic and neurological state of the patients as well as of some neuropsychological functions and quality of life, statistical significance of the results being determined. Pronounced hypotensive effect of the drug was found both in acute and late periods of stroke. Eprosartan mesilat monotherapy was effective in 75% of the patients. The most important feature proved to be a decrease of arterial pressure variability from the first days of the treatment, less frequency of secondary strokes being detected as well.
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PMID:[Antihypertensive treatment with eprosartan mesilate of patients in acute and late periods of ischemic stroke]. 1468 60

Cerebrovascular disease is a major cause of mortality world-wide, and the prevalence is expected to increase as a result of projected demographic trends. Aggressive antihypertensive therapy is one intervention that has proven highly effective in reducing the risk of stroke, with relatively small blood pressure reductions affording measurable benefit even in patients not conventionally considered hypertensive. Comparative clinical trials are revealing evidence of differential impacts of antihypertensive classes on the incidence of cerebrovascular disease that will probably be important for therapeutic choice in patients with risk factors for stroke. In particular, the role of the renin-angiotensin system in cerebrovascular disease has come under scrutiny as a result of evidence that angiotensin II receptor blockers (ARBs), but perhaps not angiotensin converting enzyme inhibitors, can reduce the risk of a first stroke to a greater degree than might be expected from their effects on blood pressure alone. Although preclinical evidence suggests that there are differential effects of the type 1 and type 2 receptor activation, the clinical relevance of this is not yet known. Furthermore, the effect on the incidence of stroke conferred by blood pressure control in the early morning hours - the time when the incidence of strokes peaks--has not been tested. Some evidence for the beneficial effect of an ARB on secondary stroke prevention comes from the MOrbidity and mortality after Stroke --Eprosartan compared with nitrendipine in Secondary prevention study (MOSES), which showed that the ARB protected against cerebro- and cardiovascular events in hypertensive patients with a previous stroke over and above the protection offered by blood pressure control. These hypotheses are among those being examined in two current large-scale trials: the Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS), and The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) Trial Programme.
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PMID:Managing the patient at risk for a second stroke. 1582 51

The angiotensin II receptor antagonist eprosartan is approved for the treatment of essential hypertension and may be administered using a convenient once-daily regimen. The drug is a well tolerated and effective antihypertensive agent with benefit in the secondary prevention of cerebrovascular events, independent of blood pressure (BP)-lowering effects. Eprosartan has a low potential for serious adverse events and has not been associated with clinically significant drug interactions, establishing it as a promising agent for combination antihypertensive strategies. Unlike ACE inhibitors such as enalapril, eprosartan does not have a tendency to cause persistent nonproductive cough. Accordingly, eprosartan represents a useful therapeutic option in the management of patients with hypertension, including those who have had a stroke and those with co-morbid type 2 diabetes mellitus.
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PMID:Eprosartan: a review of its use in the management of hypertension. 1626 4

We are currently fighting a battle against a stroke epidemic. Implementation of new treatment strategies could save many patients in the future. The control of blood pressure is a major objective; however, choosing specific antihypertensive therapy (e.g. an agent blocking the renin-angiotensin system) is also important. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrates potential benefits beyond blood pressure reduction of prescribing an angiotensin II receptor blocker (ARB) compared with more established therapy in patients with left ventricular hypertrophy (LVH). Losartan-based therapy brought about regression of LVH and reduced incidences of fatal and non-fatal stroke by 25%, new-onset diabetes by 25% and atrial fibrillation by 30% more than atenolol-based therapy for a similar blood pressure control and better tolerability. The Study on COgnition and Prognosis in the Elderly (SCOPE) study, although difficult to interpret, does not contradict an ARB benefit beyond blood pressure lowering in primary prevention linked to targeting the angiotensin type 1 receptor. The findings of the MOrbidity and mortality after Stroke, Eprosartan compared with nitrendipine in Secondary prevention (MOSES) trial suggest clear-cut ARB benefits independent of blood pressure lowering in secondary stroke prevention. Experimental findings and other clinical evidence further support the benefits of ARBs in stroke prevention. Telmisartan is an ARB with a particularly interesting profile for stroke; given the 24-hour efficacy with more pronounced protection against the morning blood pressure surge and peroxisome proliferator-activated receptor-gamma activity at clinical doses. The unique properties of telmisartan for secondary stroke prevention are being tested in the Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS) study.
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PMID:Prospects for the prevention of stroke. 1660 58

Hypertension is a common condition associated with considerable morbidity and mortality. Antihypertensive drugs reduce the risk of cardiovascular and cerebrovascular events, and may also be associated with reductions in cognitive decline. Eprosartan is an angiotensin II type 1 receptor antagonist with a unique dual mechanism of action that is approved for the treatment of essential hypertension. In clinical trials, eprosartan has been shown to significantly reduce systolic blood pressure and to be associated with significant reductions in pulse pressure in elderly patients with isolated systolic hypertension. Data suggest that blood pressure reductions achieved with eprosartan in elderly hypertensive patients are also associated with improvements in cognitive function. Eprosartan compares favorably with other classes of antihypertensive agents in terms of reductions in mortality, cardiovascular and cerebrovascular events, and stroke recurrence. Evidence suggests that eprosartan may represent a useful addition to combination drug strategies for the management of hypertensive patients with elevated cardiovascular and cerebrovascular risk.
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PMID:Unique dual mechanism of action of eprosartan: effects on systolic blood pressure, pulse pressure, risk of stroke and cognitive decline. 1803 16

Moderate elevations in blood pressure translate to significant increases in cardiovascular and cerebro vascular risk. Beneficially, this relationship allows small decreases in blood pressure to be associated with risk reduction. Both the renin-angiotensin system and the sympathetic nervous system are involved in hypertension, hence targeting these systems is likely to be of benefit in the treatment of hypertension. Angiotensin II type 1 receptor blockers (ARBs) are used for controlling blood pressure and treating heart failure in a broad range of patients, including those with diabetes and the elderly. Not only have ARBs shown good efficacy and tolerability, they also appear to have a protective effect that goes beyond that expected from the reduction of blood pressure. The ARB eprosartan is a nonbiphenyl nontetrazole angiotensin II type 1 receptor (AT1) antagonist, which acts to decrease total peripheral resistance. Eprosartan acts at vascular AT1 receptors (postsynaptically) and at presynaptic AT1 receptors, where it inhibits noradrenaline release. In clinical studies, eprosartan has been shown to significantly reduce cardiovascular and cerebrovascular events, whilst avoiding the persistent cough that commonly occurs with the use of angiotensin-converting enzyme inhibitors. Eprosartan can also be differentiated from other ARBs due to its noradrenergic effects, which other ARBs used at therapeutic doses do not possess. Eprosartan, therefore, represents a useful therapeutic option in the management of patients with hypertension, including those with a history of stroke or with co-morbid type 2 diabetes mellitus.
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PMID:Introduction: The pharmacological profile of eprosartan--implications for cerebrovascular and cardiovascular risk reduction. 1809 7


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