Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Hypertension is found among 1 to 6% of young women. Treatment aims to decrease cardiovascular risk, the magnitude of which is less dependent on the absolute level of blood pressure (BP) than on associated cardiovascular risk factors, hypertension-related target organ damage and/or concomitant disease. Lifestyle modifications are recommended for all hypertensive individuals. The threshold of BP at which antihypertensive therapy should be initiated is based on absolute cardiovascular risk. Most young women are at low risk and not in need of antihypertensive therapy. All antihypertensive agents appear to be equally efficacious; choice depends on personal preference, social circumstances and an agent's effect on cardiovascular risk factors, target organ damage and/or concomitant disease. Although most agents are appropriate for, and tolerated well by, young women, another consideration remains that of pregnancy, 50% of which are unplanned. A clinician must be aware of a woman's method of contraception and the potential of an antihypertensive agent to cause birth defects following inadvertent exposure in early pregnancy. Conversely, if an oral contraceptive is effective and well tolerated, but the woman's BP becomes mildly elevated, continuing the contraceptive and initiating antihypertensive treatment may not be contraindicated, especially if the ability to plan pregnancy is important (e.g. in type 1 diabetes mellitus). No commonly used antihypertensive is known to be teratogenic, although ACE inhibitors and angiotensin receptor antagonists should be discontinued, and any antihypertensive drugs should be continued in pregnancy only if anticipated benefits outweigh potential reproductive risk(s). The hypertensive disorders of pregnancy complicate 5 to 10% of pregnancies and are a leading cause of maternal and perinatal mortality and morbidity. Treatment aims to improve pregnancy outcome. There is consensus that severe maternal hypertension (systolic BP > or = 170mm Hg and/or diastolic BP > or = 110mm Hg) should be treated immediately to avoid maternal stroke, death and, possibly, eclampsia. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated: the risks of transient severe hypertension, antenatal hospitalisation, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by therapy, but intrauterine fetal growth may also be impaired, particularly by atenolol. Methyldopa and other beta-blockers have been used most extensively. Reporting bias and the uncertainty of outcomes as defined warrant cautious interpretation of these findings and preclude treatment recommendations.
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PMID:Treating hypertension in women of child-bearing age and during pregnancy. 1136 52

These 25 lessons 1) review the roles of plasma renin levels for causing malignant and most essential hypertension and their related vascular injuries (heart attack, heart failure, kidney failure and stroke); 2) review how antihypertensive anti-R drugs that block renin activity (beta blockers, the first converting enzyme inhibitor from venom, and the first angiotensin receptor blocker) were used to reveal plasma renin involvement in the hypertension of medium and high renin patients and to show; 3) that the 30% with low renin essential hypertension do not respond to R drugs, are not prone to heart attack or stroke, and BP is corrected instead by the natriuretic anti-V drugs (diuretics, spironolactone, CCB, alpha blockers); 4) thus, all hypertensives can be divided into R patients who have too much renin vasoconstriction or V patients who instead have predominant sodium-volume mediation. Furthermore, all antihypertensive drug classes can be divided into R drugs that block the renin factor, or V drugs that reduce body sodium volume; 5) these findings document our conception of two biochemically and physiologically different final factors that sustain all BP in which the sodium-volume factor continuously sustains cardiac output and flow while plasma renin-angiotensin sets total peripheral resistance (TPR), which, within the Poiseuille Equation (BP = cardiac output [CO] x TPR) describes our [Na+-volume x renin-angiotensin vasoconstriction] model that supports all normotension or hypertension; 6) in this light, we designed a visit-by-visit method for treating untreated hypertensives using the ambient plasma renin level and BP responses to guide primary drug therapy against either the V or R factor; and 7) for also correcting nonresponders receiving multiple drugs where renin testing correctly guides addition or subtraction of drugs depending on whether the test indicates unresponsiveness due to a reactive sodium-volume excess, or to lack of effectiveness of an R drug in a V patient or of a V drug in an R patient, or from large reactive increases in renin that override the R drug, calling for strengthening the R and/or removing V drugs. This objective, biochemically based method results in effective longterm BP control of nearly all patients using fewer, but the correct drug(s) for each individual.
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PMID:Abstract, closing summary, and table of contents for Laragh's 25 lessons in pathophysiology and 12 clinical pearls for treating hypertension. 1177 22

Since pharmacological interactions of the renin-angiotensin system appear to alter the neurological outcome of stroke patients significantly, we examined the effect of elevated levels of angiotensin II and the role of its receptor subtype AT1 in brain infarction in transgenic mice after focal cerebral ischemia. Angiotensinogen-overexpressing and angiotensin receptor AT1 knockout mice underwent 1 h or 24 h permanent middle cerebral artery occlusion (MCAO). The current study revealed a much smaller penumbra size, i.e., brain tissue at risk, in angiotensinogen-overexpressing animals compared with their wild-type subgroup after 1 h MCAO, but an enlarged infarct size after 24 h. In contrast, a smaller lesion area of energy failure and a much larger penumbral area were found in AT1 knockout mice compared with wild-type littermates. Lower perfusion thresholds for ATP depletion and protein synthesis inhibition after MCAO in AT1-deficient mice and reduced cell damage in an in vitro model using embryonic neurons of AT1 knockout mice suggest injury mechanisms independent of arterial blood pressure. Our data, therefore, demonstrate a direct correlation between brain angiotensin II and the severity of ischemic injury in experimental stroke.
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PMID:Ischemic injury in experimental stroke depends on angiotensin II. 1181 64

Proven cardiovascular benefit from angiotensin-converting enzyme (ACE) inhibition is a cornerstone of evidence-based medicine. The first study to show dramatic benefits from ACE inhibition was the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS-I), in which a 31% decrease in the rate of death was observed in patients with severe heart failure at the end of 1 year of enalapril treatment (p = 0.001). This result led to large long-term studies-including Survival and Ventricular Enlargement (SAVE), Acute Infarction Ramipril Efficacy (AIRE), Trandolapril Cardiac Evaluation (TRACE), and Study of Left Ventricular Dysfunction (SOLVD)-which verified that ACE inhibition decreases heart failure, myocardial infarction (MI), and mortality, and that striking benefit could be observed within 30 days. Short-term studies of patients in the acute phase of a heart attack verified that ACE inhibition provided rapid benefits. A meta-analysis of short-term (up to 8 weeks) studies of ACE inhibition (including CONSENSUS-II, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico [GISSI]-3, International Study of Infarct Survival [ISIS]-4, and the Chinese Captopril Study [CCS]-1) demonstrated that post-MI risk was reduced by 10% within the first day of treatment. The immediacy of the benefit suggested that ACE inhibition not only improved cardiovascular function in failing hearts but also affected important mechanisms in patients without overt heart failure. Effects on more general mechanisms of heart disease suggested that patients with problems other than hypertension or heart failure might benefit from ACE inhibitors. The Heart Outcomes Prevention Evaluation (HOPE) study investigated the hypothesis that ACE inhibition would confer benefits to patients who were at high risk for cardiovascular events, but who were without left ventricular dysfunction or heart failure. Long-term reductions in MI, stroke, cardiac arrest, and heart failure, as well as improvements in mortality, were observed in this population after treatment with ACE inhibitors. Substudies of the HOPE study revealed that ACE inhibition reduced progression of atherosclerosis and improved myocardial remodeling. Taken together, these studies provide evidence that supports treatment of a broad population of patients at risk for cardiovascular events with ACE inhibitors. The next step is to combine ACE inhibition with other treatments to maximize patient benefit. The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) will compare the efficacy of an ACE inhibitor (ramipril) with an angiotensin receptor blocker (telmisartan), and determine whether these treatments in combination will further reduce morbidity and mortality from cardiovascular disease.
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PMID:Angiotensin II and trials of cardiovascular outcomes. 1183 5

Angiotensin II type 2 (AT2) receptor is developmentally regulated and exerts antiproliferative and proapoptotic actions. Genetic ablation of this receptor in mice affects regulation of blood pressure, but the involvement of the AT2 receptor in the pathogenesis of hypertension remains unknown. In the present study, we examined developmental changes of angiotensin receptor subtypes in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP), and compared them with those in normotensive Wistar-Kyoto rats (WKY). We also investigated the regulation and functional role of the AT2 receptor in cultured mesangial cells. Receptor binding and Northern blot analyses revealed that AT2 receptor expression is significantly lower in the SHRSP kidney than in the WKY kidney during the perinatal period, while AT1 receptor expression is not different between them. In WKY mesangial cells, AT2 receptor stimulation exerted a potent antiproliferative effect; this effect was not observed in SHRSP cells lacking the AT2 receptor expression. The expression of interferon regulatory factor (IRF)-1 paralleled the growth-dependent induction of AT2 receptor in WKY mesangial cells, and transfection of IRF-1 antisense oligonucleotide significantly suppressed AT2 receptor expression, indicating IRF-1-dependent regulation of AT2 receptor expression in mesangial cells. However, this induction was inefficient in SHRSP cells. Thus, we found impaired AT2 receptor expression in the SHRSP kidney in vivo and in mesangial cells in vitro. The unbalanced expression of renal angiotensin receptor subtypes with exaggerated AT1 receptor signaling during early life in SHRSP may play a role in the programming for hypertension and related renal injury.
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PMID:Expression and role of angiotensin II type 2 receptor in the kidney and mesangial cells of spontaneously hypertensive rats. 1192 18

Increases in blood pressure (BP), particularly systolic BP, have traditionally been considered to be a normal or "physiologic" component of the aging process. However, it is now clear that elevated BP, particularly systolic BP, represents a pathophysiologic manifestation of altered cardiovascular physiology and structure, ultimately manifesting as increased cardiovascular morbidity and mortality (myocardial infarction, stroke, and total cardiovascular death rates). More than one half of the population aged 65 or older have hypertension, defined as BP > or = 140/90 mm Hg. Framingham data indicate that the risk of coronary heart disease increases with lower diastolic BP at any level of systolic BP > or = 120 mm Hg, thus further stressing the importance of pressure-induced arterial vascular compliance changes and introducing pulse pressure as an important predictor of cardiovascular risk. Geriatric hypertension is generally of a salt-sensitive nature and often associated with impaired baroreflex function. Reduction in sodium intake is important and effective in older patients, and should be initiated before or together with drug therapy. Encouraging data from clinical trials now strongly support the aggressive anti-hypertensive treatment of elderly patients. A recent meta-analysis of eight outcome trials evaluating the risks of treated and untreated isolated systolic hypertension has demonstrated a 30% reduction in combined fatal and nonfatal stroke, a 26% reduction in fatal and nonfatal cardiovascular events, and a 13% reduction in total mortality. Those drugs effective in younger patients also appear effective in the elderly; low-dose thiazides (alone or in combination with potassium sparing agents), beta blockers, long-acting dihydropyridine calcium antagonists, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all have demonstrated efficacy. In selecting an agent, it is important to consider comorbid disease states, and to recognize the potential of all nonsteroidal anti-inflammatory drugs, whether conventional or cyclooxygenase-2 specific, to increase BP or interfere with other antihypertensive agents. In general, the elderly should be treated to target BP levels identical to those suggested for younger patients, although a more gradual reduction to target, perhaps with an intermediate BP goal of < 160 mm Hg, may be advisable.
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PMID:High blood pressure in the geriatric population: treatment considerations. 1209 71

Both basic and experimental data indicate that the renin-angiotensin system through angiotensin II mediates its classic hemodynamic role, but also has a significant deleterious role in a number of cardiac, vascular, and renal disorders. Indeed, evidence indicates that angiotensin II negatively impacts endothelial function, cardiac remodeling, vessel wall hypertrophy, atherosclerosis, and progressive renal disease. Newer data point to a significant role for angiotensin II in inflammation and in inducing plasminogen activator inhibitor. This widespread negative effect can be countered by newer antihypertensive drugs, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers. Both small and large clinical trials suggest a large benefit of such drugs on not only organ-specific endpoints such as renal disease or proteinuria, but on global cardiovascular events. It does appear that when blood pressure is significantly elevated, lowering blood pressure does indeed provide protection for larger endpoints such as stroke. However, at lower blood pressure levels, a hemodynamically independent effect is likely to be contributing to the positive effects. We should embrace these effects and champion them for our patients.
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PMID:Are clinical endpoint benefits of angiotensin converting enzyme inhibitors independent of their blood pressure effects? 1211 56

Recently, we have shown that treatment of stroke-prone spontaneously hypertensive rats with angiotensin inhibitors for a limited time-window before puberty results in an attenuation of hypertensive nephrosclerosis in later life. The aim of this study was to examine the applicability of this therapeutic paradigm to a low-renin model. Dahl salt-sensitive (Dahl-S) rats were fed a high-salt diet from age 6 weeks. Some rats were treated with the angiotensin receptor blocker (ARB) candesartan cilexetil (2 mg/kg/d) from weaning to puberty (age 3-10 weeks), whereas other rats were treated continuously until overt renal damage was seen (age 3-16 weeks). Dahl-S rats on a high salt diet had increased blood pressure (207 +/- 3 vs. 125 +/- 2 mm Hg), proteinuria, and glomerular/vascular histological changes. The prepubertal treatment with ARB resulted in a continued suppression of blood pressure (153 +/- 2 mm Hg) at 16 weeks. Both proteinuria and renal histological changes were significantly (p < 0.05) attenuated, but not completely prevented by the treatment. No significant differences in plasma renin activity, renin mRNA, or AT1/AT2 mRNA were seen between groups. These results suggest that prepubertal treatment affords sustained renoprotection, even in an animal model with a suppressed renin-angiotensin system, and support the notion that appropriate prepubertal intervention may lead to a partial attenuation in the susceptibility to inherited renal diseases.
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PMID:Prepubertal treatment with angiotensin receptor blocker causes partial attenuation of hypertension and renal damage in adult Dahl salt-sensitive rats. 1213 77

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the renin-angiotensin system and exert various beneficial actions on cardiac and vascular structure and function, beyond their blood pressure-lowering effects. Randomized, controlled clinical trials have shown that ACE inhibitors improve endothelial function, cardiac and vascular remodeling, retard the anatomic progression of atherosclerosis, and reduce the risk of myocardial infarction, stroke, and cardiovascular death. Therefore, these agents are recommended in the treatment of a wide range of patients at risk for adverse cardiovascular outcomes, including those with coronary disease, prior stroke, peripheral arterial disease, high-risk diabetes, hypertension, and heart failure. ARBs are effective blood pressure- lowering and renoprotective agents and can be used in heart failure in patients who do not tolerate ACE inhibitors. The role of ARBs in the prevention of atherosclerosis and its sequelae is currently under investigation. The use of combined ACE inhibitor plus ARB therapy offers theoretical advantages over the use of each of these agents alone and is also under investigation in large, randomized clinical trials.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in atherosclerosis. 1216 36

The Study on Cognition and Prognosis in the Elderly (SCOPE) was designed to provide outcome data on cardiovascular endpoints and cognitive function in 4500 elderly hypertensive patients randomised to the angiotensin receptor blocker, candesartan, or to placebo and followed up for 4.5 years. The primary endpoint of combined cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke was not significantly reduced by active treatment (relative risk reduction 11%, p=0.19). There was also no significant difference in the decline of cognitive function between the two treatment arms. Active treatment of the placebo group (mainly hydrochlorothiazide) reduced the blood pressure differences between the treatment arms to only 3.2/1.6 mmHg, thus markedly reducing the overall power of the study. In a number of non-prespecified subgroup analyses, advantages of candesartan over placebo were reported.
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PMID:The SCOPE trial. Study on Cognition and Prognosis in the Elderly. 1222 43


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