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

To clarify how neural and humoral mechanisms operate to control cardiovascular functions in man under weightlessness, the response of sympathetic nerve activity was observed in healthy human subjects by means of microneurographic technique with the changes of several hemodynamic parameters and hormonal responses during thermoneural head-out water immersion. Muscle sympathetic nerve activity was markedly suppressed by head-out immersion, concomitantly with a reduction of the leg volume, an increase of the stroke volume and a reduction of total peripheral resistance. At the same time, plasma level of norepinephrine, vasopressive and antidiuretic hormones (ADH, aldosterone, renin activity, angiotensin I-II) were reduced, while vasodepressive and diuretic hormone (ANP) was markedly increased. The systemic blood pressure was maintained almost unchanged during head-out water immersion. The suppressive response of sympathetic nerve activity seemed to be age-dependent. This response was less prominent in the elderly than in young subjects. It is concluded that the suppressive response of muscle sympathetic activity plays an important role to maintain hemodynamic homeostasis under weightlessness to compensate for the cephalad fluid shift and the resultant increase of the stroke volume in cooperation with the hormonal responses.
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PMID:Neural and humoral controlling mechanisms of cardiovascular functions in man under weightlessness simulated by water immersion. 1153 41

A direct, continuous, and independent relation between blood pressure and the incidence of various cardiovascular events, such as stroke and myocardial infarction, is now well accepted. The increase in risk can be attributed to structural and functional changes in target organs. Central to many of these pathophysiologic processes is the renin-angiotensin system (RAS), specifically, angiotensin II. Binding of angiotensin II to angiotensin II type-1 (AT(1)) receptors produces acute vasoconstriction, leading to an increase in blood pressure. AT(1) receptor activation also contributes independently to chronic disease pathology by promoting vascular growth and proliferation, and endothelial dysfunction. These negative consequences of angiotensin II are partly counteracted by angiotensin II type-2 (AT(2)) receptor stimulation, which has favorable effects on tissue growth and repair processes. Thus, the use of selective AT(1) receptor antagonists in the treatment of hypertension has a 2-fold rationale: (1) selective AT(1) receptor blockade targets the final common pathway for all major detrimental cardiovascular actions of angiotensin II, and (2) circulating angiotensin II levels (which increase during AT(1) receptor antagonist treatment) will be free to act only at unopposed AT(2) receptors, potentially providing additional end-organ protection. Angiotensin-converting enzyme (ACE) inhibitors interrupt the RAS by preventing the conversion of angiotensin I to angiotensin II. They also increase plasma levels of bradykinin, which possesses vasodilatory and tissue-protective properties. The combination of an AT(1) receptor antagonist with an ACE inhibitor represents an appealing therapeutic strategy, because it should produce more complete blockade of the RAS, while preserving the beneficial effects mediated by AT(2) receptor stimulation and increased bradykinin levels.
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PMID:The role of the renin-angiotensin system in the development of cardiovascular disease. 1183 3

Last year, in 2001, the results of several major clinical trials have been published, concerning hypertensive patients with type 2 diabetes (IRMA, RENAAL and IDNT studies) and patients with previous strokes. Angiotensin II antagonists (irbesartan and losartan) are able to reduce the rate of progression of diabetic nephropathy in hypertensive patients with type 2 diabetes. This preventive effect occurs independently of the stage of renal dysfunction (early stage in IRMA, patent nephropathy in RENAAL and advanced nephropathy in IDNT). The PROGRESS study shows that the decrease in blood pressure, in response to an ACE inhibitor/diuretic bitherapy (perindopril/indapamide), in patients with previous minor stroke or transient ischaemic attack, reduces significantly the risk of recurrent stroke.
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PMID:[The best of 2001. Arterial hypertension]. 1190 4

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

When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction. altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:473.)
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PMID:Using ACE inhibitors appropriately. 1248 85

Angiotensin II plays a pathophysiological role for the development of cardiovascular disease. Angiotensin receptor blocker(ARB) is an antihypertensive drug that blocks the angiotensin II receptor. Recently, according to the reports of basic research, ARB has various cerebrovascular-protective-effects such as improvement of cerebrovascular auto-regulation, stroke prevention, reduction of brain edema, improvement of neurological outcome in cerebral ischemia and so on. There is no report of ARB being used for the acute stage of stroke. In an ongoing ACCESS(Acute Candesartan Cilexetil Evaluation in Stroke Survivors) trial, the ARB candesartan is being used to treat the acute stage of stroke. This trial is expected to clarify whether early treatment with candesartan during the acute stage of stroke is beneficial for the neurological outcome or prognosis.
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PMID:[Beneficial effect of ARB for ischemic stroke]. 1239 96

Angiotensin II not only is a vasoconstrictor, but it also affects cell growth and apoptosis, inflammation, fibrosis, and coagulation. Blockade of the renin-angiotensin system, either with inhibitors of the generation of angiotensin (angiotensin-converting enzyme [ACE] inhibitors) or with blockers of angiotensin receptors, reduces blood pressure and inhibits other pathophysiological actions. These other effects provide benefits in coronary heart disease, heart failure, diabetic nephropathy, and stroke beyond blood pressure reduction. These benefits were first demonstrated with ACE inhibitors. However, the mechanism of action of angiotensin receptor blockers, which block angiotensin II stimulation at the angiotensin type 1 receptor but not at the type 2 receptor, may have advantages, particularly for endothelial dysfunction and vascular remodeling, as well as cardiac and renal protection. Recent multicenter trials suggest that ACE inhibitors and angiotensin receptor blockers may reduce morbidity and mortality associated with cardiovascular and renal disease beyond blood pressure reduction. Several studies with different angiotensin receptor blockers, including comparisons with ACE inhibitors, are under way, and should provide further guidance for their clinical use.
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PMID:Vascular and cardiac benefits of angiotensin receptor blockers. 1240 36

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

Angiotensin II (Ang II) type 2 receptors (AT2Rs) have been associated with apoptosis. We hypothesized that AT2Rs are increased in stroke and may contribute effects of stroke to the brain. To test this, we have examined the expression of Ang II type 1 receptor (AT1R), AT2R and Ang II levels in the brain 24 h after transient middle cerebral artery occlusion (MCAO). The densities of AT1R and AT2R were measured by quantitative autoradiography (n=6). The levels of Ang II were measured by radioimmunoassay (RIA) (n=6) and by immunohistochemistry (n=3). AT1R levels on autoradiography showed a significant decrease (0.87+/-0.06 to 1.39+/-0.07 fmol/mg, p<0.01) in the ventral cortex of the stroke side compared to the cortices of non-stroke (NS) rats (n=4). There was no significant difference on ATIR in the contralateral verbal cortex of the stroke rats compared to NS control. In contrast, levels of AT2R in the ventral cortex of both the stroke and the contralateral sides were significantly increased (0.77+/-0.06, p<0.05 and 0.91+/-0.05, p<0.01 compared to 0.60+/-0.03 fmol/mg tissue, respectively). RIA showed that Ang II in the ventral cortex of both the stroke and the contralateral sides were significantly increased (241.63+/-47.72, p<0.01 and 165.51+/-42.59, p<0.05 compared to 76.80+/-4.10 pg/g tissue, respectively). Also, Ang II in the hypothalamus was significantly increased (179.50+/-17.49 to 118.50+/-6.65 pg/g tissue, p<0.05). Immunohistochemistry confirmed the increase of Ang II. These results demonstrate that brain Ang II and AT2Rs are increased whereas AT1Rs are decreased after transient MCAO in rats. We conclude that in stroke, Ang II and AT2R are activated and may contribute neural effects to brain ischemia.
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PMID:Expression of angiotensin type 1 and 2 receptors in brain after transient middle cerebral artery occlusion in rats. 1257 6

Angiotensin II (AngII) regulates such physiological responses as salt and water balance, blood pressure, and vascular tone, and thus plays a critical role in the pathogenesis of diabetes, hypertension, myocardial infarction, congestive heart failure, and stroke. These effects are mediated through at least three receptors: AT1R, AT2R, and AT4R, which are expressed under different developmental, tissue-specific, and disease-specific conditions and which couple to distinct effector pathways. Signaling through the AT1R, a classical G protein-coupled receptor, has been extensively studied and is well understood. Less is known about signaling through the AT2R, which often antagonizes the effects of signaling through the AT1R, but intriguing data are beginning to emerge concerning the signaling strategies and pathways that the AT2R employs.
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PMID:Angiotensin type 2 receptor (AT2R): a challenging twin. 1273 84


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