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

The active diacids of the new converting enzyme (CE) inhibitors ramipril and perindopril proved to possess a similar inhibitory potency against rat plasma CE in vitro. Both diacids were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for 2 weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system [angiotensin I (ANG I), angiotensin II (ANG II), PRC and CE activity] followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three CE inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril did. These results are consistent with the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.
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PMID:Antihypertensive action and inhibition of tissue converting enzyme (CE) by three prodrug CE inhibitors, enalapril, ramipril and perindopril in stroke-prone spontaneously hypertensive rats. 302 91

Ramipril and perindopril, the active diacids of two new converting enzyme (CE) inhibitors proved to possess a similar inhibitory potency against rat plasma CE in vitro. These diacid compounds were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for two weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg per day) normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system (angiotensin I, angiotensin II, PRC, CE activity) followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril. These results confirm the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.
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PMID:[Antihypertensive action and inhibition of tissue conversion enzyme by ramipril, perindopril and enalapril in the spontaneously hypertensive rat (SHRSP)]. 302 75

Male rabbits received 20 micrograms/ml of cadmium in drinking water for nine months. At the end of the treatment aortic vascular resistance was increased, whereas maximum rate of increase in left ventricular pressure, aortic blood flow, stroke volume, cardiac output, left ventricular minute work, and left ventricular stroke work were reduced. Arterial blood pressure, heart rate, and the index of myocardial oxygen consumption were not modified. The exposed rabbits also showed reduced pressor responses to vagotomy, increased cardiovascular responses to angiotensin I and II and isoprenaline, and lower responses to serotonin and guanethidine; the bradycardia induced by clonidine was augmented; the cardiovascular effects of bilateral carotid occlusion, hexamethonium, phenylephrine, histamine, acetylcholine, tyramine, papaverine and verapamil were unaltered. In the treated rabbits cadmium was appreciably higher in the kidney than in the heart; however, renal concentrations of cadmium were lower than those reported as critical for workers exposed to cadmium. Zinc was increased in the kidney but not in the heart, whereas copper remained unchanged in the examined organs. In rabbits treated with cadmium the increased aortic vascular resistance and the reduced myocardial contractility contribute to preserve a haemodynamic equilibrium without alteration of blood pressure and heart rate; the question of whether a similar condition may be present in people exposed to cadmium with normal cardiovascular parameters is discussed.
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PMID:Mechanisms of cardiovascular regulation in male rabbits chronically exposed to cadmium. 375 11

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

Intraocular pressure (IOP) and arterial blood pressure (BP) were recorded manometrically in normotensive Wistar Kyoto rats (NR) and stroke-prone spontaneously hypertensive rats (SHR). IOP was significantly lower in SHR (7.8 +/- 0.2 mm Hg) compared to NR (15.9 +/- 0.4 mm Hg). In NR, administration of vasoactive substances (kallikrein, bradykinin, angiotensin I and II) or bloodletting resulted in significant IOP reactions, which ran nearly parallel to the acute BP changes. In SHR, however, IOP showed little reaction after comparable changes in BP. The cause of the low IOP in SHR is unknown. It is assumed that in SHR rarefaction of arterioles and capillaries and a decrease in the compliance of eye vessels, in combination with an increase in the distensibility of the bulbus at this low IOP level, contribute to the lack of IOP response after administration of vasoactive drugs.
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PMID:Intraocular pressure and systemic blood pressure after administration of vasoactive substances in hypertensive and normal rats. 384 58

12 patients with primary hypertension not adequately controlled on combined treatment with diuretics, beta-adrenergic blocking drugs and hydralazine were included in the study. The patients were hospitalised and hydralazine discontinued. The diuretic and beta-blocking medication was given about 1 hour prior to the short term experiments and, following baseline measurements, an oral solution of felodipine (0.075-0.1 mg/kg) was ingested. Cardiac output was measured (dye dilution technique) and continuous monitoring of intra-aortic blood pressure (brachial artery) was performed. In 10 patients, changes in renal plasma flow (para-aminohippuric acid clearance) and glomerular filtration rate (51Cr-EDTA-clearance) were followed over a short period, and in 6 patients repeated after 5 to 7 months. Plasma renin activity (radioimmunoassay of angiotensin I) was followed, as was plasma concentration of felodipine. A significant hypotensive response was seen only 15 minutes after intake of felodipine. The maximal response occurred after 30 minutes when mean arterial blood pressure was reduced by 24% (from 132 to 102 mm Hg). There was a linear relationship between the change in mean arterial blood pressure and log plasma concentration of felodipine. Cardiac output increased from 5.1 +/- 1.5 to 6.6 +/- 2.6 L/min (p less than 0.01), partly because of increased heart rate from 56 +/- 7.9 to 65 +/- 9.5 beats/min (p less than 0.01) and partly due to increased stroke volume from 93 +/- 25 to 103 +/- 34 ml/beat (p less than 0.05). Renal plasma flow increased significantly (p less than 0.05) from 343 +/- 138 ml/min to 391 +/- 154 ml/min and 400 +/- 149 ml/min, while glomerular filtration rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Felodipine. A calcium-inhibiting vasodilator in refractory hypertension. 388 56

1. Long-lasting haemorrhagic hypotension (4.5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP(9a)), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP(9a) was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days.2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock.3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock.4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period.5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock.6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period.7. BPP(9a) had no measurable effect on the course of endotoxic shock.8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed.
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PMID:On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock. 437 70

Enalapril maleate is a prodrug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat. Enalapril maleate is 60% absorbed and 40% bioavailable as enalaprilat. Both compounds undergo renal excretion without further metabolism. The functional half-life for accumulation of enalaprilat is 11 h, and this is increased in the presence of a reduction in renal function. Inhibition of converting enzyme inhibition is associated with reductions in plasma angiotensin II and plasma aldosterone, and with increases in plasma renin activity and plasma angiotensin I. Acute and chronic effects have been reviewed. When given with hydrochlorothiazide, enalapril attenuates the secondary aldosteronism and ameliorates the hypokalaemia from diuretics. Both acutely and chronically in patients with essential hypertension, enalapril reduced blood pressure with a rather flat dose-response curve. No evidence of a triphasic response such as seen with captopril has been demonstrated with enalapril, and blood pressure returns smoothly to pretreatment levels when the drug is abruptly discontinued. Once- or twice-daily dosing gives similar results. The antihypertensive effects of enalapril are potentiated by hydrochlorothiazide. Haemodynamically, blood pressure reduction is associated with a reduced peripheral vascular resistance and an increase in cardiac output and stroke volume with little change in heart rate. Renal vascular resistance decreases, and renal blood flow may increase without an increase in glomerular filtration in patients with normal renal function. In patients with essential hypertension and glomerular filtration rates below 80 ml/min/m2, both renal blood flow and glomerular filtration rates may increase.
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PMID:An overview of the clinical pharmacology of enalapril. 609 37

Renin is stored in synaptosomes of rat brain, separately from cathepsin D and intraneuronal angiotensin II (ANG II) has been demonstrated with the electron-microscope. Although the subcellular localization of other components of the renin-angiotensin system (RAS) have still to be investigated, these data suggest possible intracellular synthesis of ANG II in the brain. Brain ANG II is biochemically identical to the plasma peptide and corresponds to (IIe) 5-ANG II. The peptide level is unchanged after bilateral nephrectomy, and angiotensin I (ANG I) accumulation is observed in nephrectomized animals following brain angiotensin converting enzyme blockade. The significantly greater accumulation of ANG I and reduction of ANG II in stroke prone spontaneously hypertensive Wistar-Kyoto rats (WKY) indicates a higher synthesis and turnover rate of ANG II in SHR. Most converting enzyme inhibitors (CEI) penetrate the brain after chronic oral treatment. Part of their blood pressure lowering action may therefore be explained by an inhibition of the brain RAS.
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PMID:The brain angiotensin system: subcellular localization and interferences with converting enzyme inhibitors. 610 Jun 13

The effects of various doses of the converting enzyme inhibitor captopril injected into the lateral brain ventricle (i.c.v.) and intravenously (i.v.) on blood pressure (BP) and on converting enzyme activity were tested in stroke prone conscious spontaneously hypertensive rats (SHR-sp) and in normotensive Wistar Kyoto rats (WKY). Injection of 500 micrograms captopril i.c.v. produced a marked biphasic BP effect in SHR-sp, an initial increase followed by a long-lasting decrease. Only the initial BP increase was observed in WKY. The pressor responses to i.c.v. angiotensin I (ANG I) were completely blocked after i.c.v. captopril injection and this effect lasted for 24 h. The pressor responses to i.v. ANG I were also inhibited immediately after 500 micrograms captopril i.c.v. and gradually returned to control values within 5 h. Intravenous injections of 500 micrograms captopril almost completely inhibited the pressor responses to i.v. ANG I; they caused a moderate BP decrease in SHR-sp and had no significant BP effects in WKY. In SHR-sp, 5 micrograms captopril i.c.v. caused a reduction of BP with a concomitant inhibition of the pressor effects of i.c.v. ANG I. Both effects lasted about 30 min. The pressor responses to i.v. ANG I were not inhibited. In WKY, 5 micrograms captopril i.c.v. had no effect on BP. It is concluded that captopril can reduce BP by action on the brain without peripheral inhibition of converting enzymes. Following high doses injected i.c.v., the inhibitor leaks into the periphery but this cannot explain the marked hypotensive effect in SHR-sp.
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PMID:Brain converting enzyme inhibition: a possible mechanism for the antihypertensive action of captopril in spontaneously hypertensive rats. 626 38


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