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

We determined the acute hypotensive effect of a single administration and the prophylactic effect of chronic treatment with Irbesartan, an angiotensin II receptor antagonist, on the development of end-organ damage in stroke-prone spontaneously hypertensive rats (SHRSP). The acute hypotensive effect was determined by a telemetrical method in SHRSP fed a normal diet. The prophylactic effect was examined by biochemical, histopathological and immunohistochemical methods in SHRSP fed a high-salt and low-protein diet. Irbesartan (3, 10, 30 and 100 mg/kg) reduced blood pressure in a dose-dependent manner without affecting heart rate. Irbesartan (3, 10 and 30 mg/kg) increased the survival rate in SHRSP fed a high-salt and low-protein diet. Furthermore, Irbesartan ameliorated the appearance of stroke symptoms in dose-dependent manner showing association with the prevention of microscopic lesions. Irbesartan ameliorated the increases in urinary protein excretion and N-acetyl-D-glucosamidase activity by preventing nephrosclerosis, as judged by microscopic observations, and ameliorated the increases in the expression of collagen IV and fibronectin in the kidney. These findings demonstrate that Irbesartan is a potent antihypertensive drug offering a protective effect on the development of hypertension-induced end-organ damages in SHRSP. Thus, Irbesartan is useful for the therapy of hypertension with end-organ damage.
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PMID:Hypotensive and prophylactic effects of angiotensin II subtype 1 receptor antagonist, irbesartan, in stroke-prone spontaneously hypertensive rats. 1500 Feb 95

Diabetes mellitus and impaired glucose tolerance (IGT) are common disorders, and their prevalence is predicted to increase over the next several decades. The major serious complication of these disorders is large vessel atherosclerosis leading to myocardial infarction and stroke. Aggressive control of hypertension and dyslipidemia can significantly reduce risk for cardiovascular events, but a large amount of residual cardiovascular disease remains. A major remaining question is the potential role of aggressive glucose control for reducing macrovascular event rates in patients with diabetes. An ongoing trial addresses this issue, and a large number of other concurrent trials address several novel therapeutic strategies to reduce further the cardiovascular complications of diabetes or IGT. Many of these strategies test approaches that may directly target the vessel wall. Therapeutic modalities currently being evaluated include thiazolidinediones, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. Most of these trials will report their findings in the next 5 years. It is likely that the results of ongoing trials will significantly improve our approach to managing cardiovascular risk in patients with diabetes and IGT.
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PMID:Strategies in ongoing clinical trials to reduce cardiovascular disease in patients with diabetes mellitus and insulin resistance. 1517 14

Hypertensive crises are situations when arterial hypertension shows its immediate damaging potential, and in such circumstance, antihypertensive therapy provides its life-saving effectiveness. Among these situations are hypertensive emergencies, hypertensive urgencies, hypertensive encephalopathy, and also accelerated-malignant hypertension characterised by the presence of grade 3 or grade 4 Keith-Wagener retinopathy and numerous complications (acute renal failure, heart failure, haemorrhagic brain stroke or acute coronary events). Despite of antihypertensive therapy, the mortality rate of accelerated-malignant hypertension is about 25% after the 5th year. We present the case of a thirty-three years old male, with a five-year history of non-treated hypertension, who develops accelerated- hypertension with heart failure, microangiopathic haemolytic anaemia and renal failure that requires renal replacement therapy. After a strict control of blood pressure; initially using parenteral agents such as Solinitrin and Urapidil, followed by angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers, calcium channel blockers and Hydralazine, the patient partially recovers his renal function, resulting in the withdrawal of haemodialysis.
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PMID:[Accelerated arterial hypertension in a young male]. 1521 76

Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence in United States and European general population surveys ranges from 6% to 10%. Increased risk for cardiovascular morbidity and mortality begins with albumin excretion rates that are well within normal limits. Although microalbuminuria interacts with the traditional cardiovascular risk factors, it has an independent relationship to renal and cardiovascular outcomes. For example, microalbuminuria doubles the risk for a cardiovascular event in patients with type 2 diabetes mellitus even after adjusting for the usual risk factors. Elevated rates of urinary albumin excretion predict target organ damage, notably renal disease, but are also related to left ventricular dysfunction, stroke, and myocardial infarction. Screening for microalbuminuria, which is recommended by several expert committees and associations, has become a readily accessible procedure. Screening can give clinicians prognostic information concerning cardiovascular risk and assist in guiding therapy. The goal of treatment is to prevent progression of, and even to reverse, microalbuminuria. Abundant evidence demonstrates that antihypertensive therapy is an important key to the control of urinary albumin excretion, and blockade of the renin-angiotensin system (with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is the treatment of choice. These drugs have successfully halted or delayed the progression to nephropathy and have reversed elevated rates of albumin excretion to normal values, even when blood pressure reduction has been minimal.
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PMID:Microalbuminuria and cardiovascular risk. 1548 65

The initial view of the renin-angiotensin system focused on the role of angiotensin II as a hormone involved in blood pressure control, based on its role in renal salt and water regulation, as well as central nervous system (thirst) and vascular smooth muscle tone. Subsequent data showed a role for angiotensin II in long-term effects on cardiovascular structure, including cardiac hypertrophy and vascular remodeling. Importantly, recent human studies with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have demonstrated exciting clinical benefits including decreases in incidence of stroke, diabetes, and end-stage renal disease that suggest important new mechanisms of action. In this review, we focus on new roles for the renin-angiotensin system in the endothelium based on the concepts of diverse signals and effects mediated by multiple angiotensin I- and angiotensin II-derived peptides, multiple angiotensin metabolizing enzymes, multiple receptors, and vascular bed-specific intracellular signals.
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PMID:Angiotensin II and the endothelium: diverse signals and effects. 1563 47

Angiotensin II plays a significant role in cell growth and proliferation in model systems and in humans. Numerous studies have shown that left ventricular hypertrophy (LVH) increases the risk of coronary heart disease, congestive heart failure, stroke or transient ischemic attack; all-cause deaths, and sudden death. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has provided beneficial effects on LVH regression and on cardiac remodeling in the presence of hypertension and heart failure. The new class of ARBs appears to provide cardioprotective effects that are similar to those of the ACE inhibitors. Most of the beneficial effects provided by these agents appear to be related to a more complete blockade of the angiotensin II type 1 (AT1) receptor. However, costimulation of the angiotensin II type 2 (AT2) receptor appears to increase nitric oxide and thus causes some bradykinin-like effects. Evidence for the role of angiotensin II in promoting LVH as well as abnormal regulation of the angiotensin II signal transduction pathways in model systems and in humans has been reviewed. Secondly, the mechanisms for the beneficial effects of angiotensin II receptor blockers studied in model systems and in humans, including possible involvement in the formation of reactive oxygen species by mononuclear cells, are presented. Finally, results from large-scale interventions such as the Losartan Intervention For Endpoint reduction (LIFE) study, as well as an overview of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial involving the use of ARB in high-risk patients, are presented.
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PMID:Left ventricular hypertrophy and angiotensin II receptor blocking agents. 1563 45

There is increasing evidence that combination therapy should be emphasized more than it is at present for the initial treatment of hypertensive patients. Recent guidelines acknowledge the value of combination therapy, although some treatment algorithms fail to echo this message. Observations from major clinical trials in the elderly, diabetics, stroke patients, and African Americans all indicate that combination therapy is necessary to control blood pressure in the majority of these patients. Several combination therapies such as an angiotensin II receptor blocker and a diuretic, an angiotensin-converting enzyme inhibitor with a diuretic, a beta blocker with a diuretic, or an angiotensin-converting enzyme inhibitor with a calcium antagonist have been shown to be effective in patients who do not respond to monotherapy. The current review focuses on the newest such combination; an angiotensin II receptor blocker and a diuretic may have an added advantage of being well tolerated. Recent studies have shown that angiotensin II receptor blockers, given alone or combined with a diuretic, may prevent some cardiovascular outcomes independent of their blood pressure-lowering efficacy.
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PMID:Combination therapy in the management of hypertension: focus on angiotensin receptor blockers combined with diuretics. 1572 54

The metabolic syndrome is a worldwide epidemic, setting the stage for type 2 diabetes and its microvascular complications, and acceleration of macrovascular disease. Insulin resistance, hyperglycemia, dyslipidemia, hypertension, thrombotic disorders and adiposity define the metabolic syndrome and contribute to endothelial dysfunction and, subsequently, to accelerated atherosclerosis. Angiotensin II contributes to the development and progression of cardiovascular and renal endpoints and, as such, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors demonstrate a protective effect. Ligands for the peroxisome proliferator-activated receptor gamma (PPAR gamma), appear to impact favourably on atherosclerosis through both direct and indirect mechanisms. In humans, these ligands improve endothelial function, attenuate albuminuria and hypertension, and potentially prevent conversion of prediabetes to type 2 diabetes. Statins also have proven benefit in decreasing overall cardiovascular and stroke mortality and morbidity. The combination of angiotensin II blockade, statin therapy and PPAR gamma activation might emerge as an important global therapeutic strategy in the metabolic syndrome and diabetes. Further studies are needed to determine whether they have synergistic effects to protect the vasculature.
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PMID:Metabolic syndrome-interdependence of the cardiovascular and metabolic pathways. 1578 Aug 21

Left ventricular hypertrophy (LVH) is a potent, independent predictor of cardiovascular events, particularly in hypertension, in which it dramatically increases the risk of stroke, coronary heart disease and heart failure. LVH is predominantly a surrogate marker for the effects of other risk factors integrated over time, but it may also contribute directly to cardiovascular disease through pathological changes in cardiac structure. The influence of blood pressure is central to LVH pathology, with 24-h blood pressure being more predictive of LVH than single clinic measurements. Blood pressure variation throughout the day is also emerging as an important correlate of LVH, and a strong association has been found between the early morning blood pressure rise and increased left ventricular mass. Antihypertensive treatment can reverse LVH, and preliminary studies suggest that this improves cardiovascular outcome and long-term prognosis. Most classes of antihypertensive agent show some effect on LVH regression, with the notable exceptions of minoxidil and hydralazine. However, many of the data regarding LVH regression come from small, poor-quality trials or from meta-analyses of these studies. In the few well-conducted studies that are available, certain classes of antihypertensive drugs are more effective than others. Those that target angiotensin II, such as the angiotensin II receptor blockers, appear to have a specific action on LVH that is independent of blood pressure reduction. Further high-quality studies are needed to define how LVH predicts cardiovascular risk, which agents are most effective at eliciting LVH regression and how such reversal can affect cardiovascular outcome.
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PMID:Left ventricular hypertrophy as a predictor of cardiovascular risk. 1582 48

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


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