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

The actions of angiotensin II can be described in terms of the three paradigms listed in Table 1. According to the first paradigm (organ physiology), angiotensin II is a pressor, while the second (cell biochemistry) views it as an extracellular messenger that, by promoting Ca2+ release within cells, causes vasoconstriction and a weak positive inotropic response by the heart. However, neither of these paradigms fully explains the remarkable ability of angiotensin converting enzyme inhibitors to improve the prognosis for patients with heart failure. To account for these clinical effects of angiotensin converting enzyme inhibitors, we will probably need to invoke the third paradigm (gene expression), which views angiotensin II as a growth factor that promotes and modifies protein synthesis. Angiotensin II, therefore, should probably not be viewed simply as a vasoconstrictor with a side effect to promote hypertrophy, but instead as a growth factor that, because it utilizes Ca2+ to mediate its effects on gene expression, also increases smooth muscle tone and myocardial contractility. This view of angiotensin II as a growth factor helps us to understand the clinical benefit of angiotensin converting enzyme inhibitors as arising from inhibition of maladaptive changes in the failing heart (gene expression) as well as from the reduced afterload (organ physiology) that results from decreased smooth muscle tone (cell biochemistry).
Heart Dis Stroke
PMID:Is angiotensin II a growth factor masquerading as a vasopressor? 134 1

Many studies in experimental animal models suggest that there is an interaction between angiotensin II and the sympathetic nervous system. We have now sought evidence for such an interaction using angiotensin II and beta-adrenoceptor stimulation with isoprenaline. Ten normal volunteers were infused with placebo/placebo, placebo/angiotensin II, placebo/isoprenaline and angiotensin II/isoprenaline in a randomized single-blind fashion. Isoprenaline alone caused a non-significant 11-20% rise in stroke volume. Angiotensin II alone caused no significant change in stroke volume. However, the combination of angiotensin II/isoprenaline caused a significant increase in stroke volume of 31-55% (p less than 0.01), and this increase was significantly greater than with isoprenaline alone (P less than 0.02, by repeated-measures analysis of variance). This occurred with no difference in heart rate change. Isoprenaline significantly reduced total peripheral resistance and this reduction was not affected by concomitant infusion of angiotensin II. This study provides evidence that a physiological dose of angiotensin II can synergistically augment the stroke volume effect of beta-agonism in man. There are several possible mechanisms, but a regional redistribution of venous blood which causes increased cardiac filling seems likely.
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PMID:Angiotensin II augments the stroke volume response to isoprenaline in man. 166 62

Arteriosclerosis is the hallmark of hypertension and of its complications, namely stroke, coronary artery disease and ischaemic renal failure. The earliest morphological change in the arteriosclerotic process is vascular smooth muscle hypertrophy and hyperplasia. Angiotensin II is an important growth factor in vascular smooth muscle cells. The chronic administration of ACE inhibitors will reverse many of the changes of vascular hypertrophy in experimental animal models, and will improve vascular compliance in hypertensive patients. Some differences have been reported between different ACE inhibitors with respect to blood pressure-lowering effect and regression of medial hypertrophy in spontaneously hypertensive rats.
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PMID:Reversal of structural changes in hypertensive arteries--a major prospect for the future. 192 14

Endothelium of cerebral surface vessels (pial arterioles and venules) was injured with a light/dye technique in anesthetized mice. This induced platelet aggregation at the site of injury. The onset of aggregation was monitored through a microscope in mice given angiotensin II acetate, 4 micrograms i.v. 30 minutes earlier. Aggregation latency was compared with that in vehicle treated (saline) mice. Angiotensin II caused a highly significant delay in aggregation within the arterioles which was not related to a change in shear rate of blood. Angiotensin II added to platelet rich plasma, failed to influence the aggregation produced by subsequent addition of 0.5 microM ADP or 0.5 mM sodium arachidonate. Angiotensin is a well known stimulator of prostacyclin synthesis or release, and angiotensin has been reported to inhibit platelet aggregation ex vivo by increasing prostacyclin in the effluent superfusing the mass of aggregating platelets. Our data represent the first report of an antiaggregating effect of angiotensin II in vivo in an intact microvascular bed. The data is consonant with the literature describing increased prostacyclin levels following angiotensin II infusion. The antiaggregating effect of angiotensin in cerebral microvessels may help explain a recent observation describing increased survival of gerbils treated with angiotensin following carotid ligation.
Stroke
PMID:Angiotensin delays platelet aggregation after injury of cerebral arterioles. 381 Jul 22

Angiotensin II (ANG II)-sensitive septal neurons in the brain of stroke-prone spontaneously hypertensive rats (SHR-sp) and of normotensive Wistar-Kyoto rats (WKY) were investigated for possible differences at receptor sites. ANG II, the competitive ANG II-antagonist saralasin, and acetylcholine (ACh), were applied microiontophoretically onto neurons of the lateral septal area. ANG II-evoked neuronal firing which was specifically inhibited by saralasin occurred at a significant lower threshold in SHR-sp (23%) and showed an extended postactivity (340%) as compared to the age-matched WKY controls. In contrast, the activity due to ACh remained similar in both strains.
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PMID:Increased sensitivity of neurons to angiotensin II in SHR as compared to WKY rats. 629 59

Angiotensin II (Ang II) is the primary mediator of the renin-angiotensin system (RAS). Inappropriate control of the RAS is critically involved in the development and maintenance of hypertension and congestive heart failure. The actions of Ang II are thought to be mediated by specific surface receptors on the various target organs. At present, two receptors for Ang II have been firmly established in mammals, including man. According to current nomenclature, losartan represents the prototype antagonist of the Ang II type 1 (AT1) receptor and does not possess significant affinity for the so-called AT2 receptor. Losartan is the first of a new class of orally active, nonpeptide Ang II receptor antagonists able to very specifically and selectively inhibit the RAS while lacking the agonistic effects of the peptide receptor antagonists, e.g. sarlasin, or the bradykinin potentiating effects of the angiotensin converting enzyme (ACE) inhibitors. Virtually all of the known actions of Ang II, e.g. those defined by Ang II itself, saralasin, ACE or renin-inhibitors are blocked by losartan, emphasizing the major role of this distinct Ang II receptor subtype in mediating the responses of Ang II. The functional correlate of the AT2 receptor remains poorly understood. In several models of experimental and genetic hypertension, AT1 receptor antagonists are effective antihypertensive agents with similar efficacy to that of ACE and renin-inhibitors. In animal models of renal disease, AT1 receptor antagonists significantly decrease proteinuria, protect against diabetic glomerulopathy and increase survival in stroke-prone spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new class of therapeutic agents: the angiotensin II receptor antagonists. 763 3

To investigate the role of autonomic reflexes in stroke-work optimization, we studied ventriculoarterial coupling in unanesthetized dogs with the autonomic system intact and blocked. Ventricular contractility was quantified by the slope of the end-systolic pressure-volume relation, ventricular elastance (Ees). Arterial system properties were quantified by the ratio of end-systolic pressure to stroke volume, arterial elastance (Ea). The coupling between left ventricle and arterial system was expressed by the Ea-to-Ees ratio. Changes in arterial blood pressure during nitroprusside or angiotensin II infusion were used to elicit reflex-mediated influences on ventriculoarterial coupling. With the autonomic system intact, Ees doubled during nitroprusside infusion while Ea remained unchanged due to reactive vasoconstrictor forces and tachycardia. Consequently, the Ea-to-Ees ratio fell 50% from baseline. Angiotensin II infusion increased Ea 46% but did not significantly change Ees, resulting in a 26% increase in the Ea-to-Ees ratio. In contrast to ventriculoarterial coupling, stroke work was insensitive to changes in afterload, remaining close to its theoretical maximum. After autonomic blockade, Ees tended to decrease during nitroprusside and increased during angiotensin II infusion in parallel with changes in Ea, so that the Ea-to-Ees ratio did not change from baseline as much as it did with the autonomic system intact. Again, the left ventricle maintained nearly 90% of its maximal stroke work. Thus, over a wide range of afterload, stroke work was kept near its theoretical maximum, independent of autonomic neural regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neural modulation of ventriculoarterial coupling in conscious dogs. 814 75

Through the multiple actions of angiotensin II (AII), the renin-angiotensin system (RAS) participates in cardiovascular homeostasis. Angiotensin II acts by binding to specific membrane-bound receptors, which are coupled to one of several signal transduction pathways. These AII receptors exhibit heterogeneity, represented by AT1 and AT2 receptor subtypes. The AT1 receptor mediates the major cardiovascular action of the RAS. This receptor has been cloned from multiple species, disclosing features consistent with a transmembrane, G-protein-linked receptor. Further AII receptor heterogeneity is evident by the cloning of isotypes of the AT1 receptor. Blocking the interaction of AII with its receptor is the most direct site to inhibit the actions of the RAS. Many AII receptor antagonists, including peptide analogs of AII and antibodies directed against AII, possess unfavorable properties that have limited their clinical utility. The discovery and further development of imidazole compounds with AII antagonist properties and favorable characteristics, however, has promise for clinical utility. The leader in this field is a selective AT1 receptor antagonist losartan (previously known as DuP 753 or MK-954). Losartan was demonstrated to be an effective antagonist of many AII-induced actions and an effective antihypertensive agent in many animal models of hypertension (HTN). Losartan also demonstrated secondary benefits in preventing stroke, treating congestive heart failure (CHF), and delaying the progression of renal disease in animal models. Clinical studies confirm the AII antagonist action of losartan and suggest that losartan will be effective in the treatment of essential HTN. AII antagonism is likely to provide useful treatment in essential HTN and CHF, conditions in which the RAS is known to play a major role. The utility of AII antagonism may extend beyond that of HTN and CHF, as suggested by the potential usefulness of angiotensin-converting enzyme (ACE) inhibition in the treatment or prevention of many other diseases. The key advantage AII antagonists provide over ACE inhibitors is that they may avoid unwanted side effects, related to bradykinin potentiation with the latter drugs. The AII antagonists will help determine the role of the RAS in physiologic regulation and in the pathophysiology of various disease states.
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PMID:Angiotensin II receptor blockade: an innovative approach to cardiovascular pharmacotherapy. 830 Aug 85

Antihypertensive treatment with diuretics and/or beta-blockers lowers stroke and coronary heart disease morbidity and mortality. However, although the newer antihypertensives induce effective control of blood pressure and regression of hypertensive organ damage, it has not been proven whether they reduce mortality. Ongoing clinical trials such as STOP II, CAPPP, NORDIL, INSIGHT, ALLHAT and LIFE test whether antihypertensive regimens with ACE-inhibitor, calcium-blocker, alpha-blocker and Angiotensin II-antagonist are equally good or possibly even better than diuretics and beta-blockers in preventing cardiovascular complications. The HOT trial clarifies how much the diastolic blood pressure should be lowered, and whether a small dose of aspirin has a protective effect when combined with optimal control of blood pressure. These studies should give better guidelines for the treatment of hypertension.
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PMID:[Status of ongoing controlled clinical trials on hypertension]. 1535 9

HYPERTENSION-ASSOCIATED ABNORMALITIES THAT PROMOTE CORONARY DISEASE: Although antihypertensive treatment has been effective in reducing premature cardiovascular mortality, the effect on various organ-specific morbid events has been unequal; the effect is much more impressive on stroke reduction than on reduction of coronary events. A student of pathophysiology would have anticipated such an outcome since blood pressure elevation is only one of multiple abnormalities in hypertension. Even in its mildest form hypertension is associated with the metabolic syndrome of dyslipidemia/insulin resistance which is conducive to early atherosclerosis. A large proportion of patients also have increased sympathetic and decreased parasympathetic tone, a constellation conducive to arrhythmias and, ultimately, to sudden death. An elevated hematocrit is also found in a substantial proportion of male patients and excessive platelet aggregability has also been described in hypertension. These hematologic abnormalities are conducive to coronary thrombosis. Angiotensin II and norepinephrine, two of the most potent trophic hormones, are frequently elevated in hypertension. The effect of these hormones on the cardiac and vascular structure further increases the predilection for negative outcomes. Left ventricular hypertrophy is a potent risk factor of coronary mortality, congestive heart failure and sudden death. Vascular hypertrophy reduces the coronary reserve and at the level of skeletal muscles contributes to the evolution of the metabolic syndrome. ORGAN-SPECIFIC HYPERTENSION TREATMENT: Because of these abnormalities we are entering a new era of treatment in hypertension. Whereas an effective fall in blood pressure remains the main goal of treatment, differential effects of various antihypertensive agents on organ-specific morbidity are being actively explored. If this research proves that certain drugs have a specific advantage in defined subgroups of patients, clinical practice will change. It is reasonable to expect that in the next century we will witness a further improvement in the impact of antihypertensive treatment on public health.
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PMID:Coronary disease in hypertension: a new mosaic. 921 91


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