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

1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.
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PMID:A novel orally active converting-enzyme inhibitor YS 980: effects on blood pressure in spontaneously hypertensive rats. 23 20

1. Captopril (25 mg) reduced plasma angiotensin II (ANG II) by 53% (P less than 0.001) and mean brachial artery pressure (MBAP) by 18.7 mmHg (P less than 0.001) within 75 min in 26 hypertensive patients. After 2 months (on 150-600 mg/day) MBAP had decreased by 27.1 mmHg (n = 18) with no further change of plasma ANG II. delta MBAP was significantly related to control log plasm renin (PRA) and log ANG II in both conditions. 2. The acute depressor response to captopril was 11.2 mmHg greater (P less than 0.001) than delta MBAP during saralasin infusion (n = 12). 3. Heart rate slightly increased after acute administration of captopril (+3.3 beats/min; P less than 0.005), but cardiac output was not significantly affected; systemic vascular resistance decreased by 10% (P less than 0.01) with unchanged pulmonary vascular resistance. 4. During chronic administration, oxygen consumption, cardiac output and stroke volume increased by 15% (P less than 0.01), with unchanged heart rate; systemic vascular resistance had dropped by 30% (P less than 0.001). 5. Plasma ANG II and plasma aldosterone decreased, and PRA and ANG I increased acutely, with no further changes during chronic treatment.
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PMID:Haemodynamic effects of captopril in hypertensive patients: comparison with saralasin. 39 66

To examine the possible activation of prorenin in the circulation, recombinant rat prorenin was intravenously given to pentobarbital-anesthetized rats. Bolus injection of prorenin at the dose of 100 micrograms angiotensin I (ANG I).h-1.kg-1 into Wistar rats, leading to a 15-fold increase in plasma prorenin concentrations (from 27 +/- 6 to 393 +/- 75 ng ANG I.h-1.ml-1) at 5 min after the injection, did not affect blood pressure, heart rate, and plasma active renin concentrations throughout experiments. On the other hand, the administration of active renin at the dose of 1, 3, and 10 micrograms ANG I.h-1.kg-1 increased mean blood pressure of Wistar rats by 8 +/- 2, 15 +/- 2, and 27 +/- 4 mmHg, respectively. Similar results were obtained in Wistar rats at 18 h after bilateral nephrectomy. These results confirmed no activation of prorenin in the circulation of normotensive rats. The activation of prorenin was also examined on both stroke-prone spontaneously hypertensive rats (SHRSP) and 18 h-nephrectomized SHRSP. There was no rise in blood pressure or plasma active renin concentrations in both groups of SHRSP after injection of prorenin. Thus the elevated plasma active renin in SHRSP [Shibota, M., A. Nagaoka, A. Shino, and T. Fujita. Am. J. Physiol. 236 (Heart Circ. Physiol. 5): H409-H416, 1979] seems to be caused by the enhanced release of active renin from the kidney rather than the activation of circulating prorenin.
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PMID:Effects of prorenin on blood pressure and plasma renin concentrations in stroke-prone spontaneously hypertensive rats. 153 51

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.
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PMID:Systemic hemodynamic effects of endothelin in rats. 218 Mar 22

Intracerebroventricular (ivt) angiotensin II (ANG II) at 0.4, 2, 10, and 50 ng.kg-1.min-1 increased arterial pressure in conscious sheep in a dose-related manner (26 mmHg, P less than 0.05, at 50 ng.kg-1.min-1). Total peripheral resistance (TPR) and right atrial pressure also increased. Heart rate, stroke volume, and cardiac output did not change. Pressor responses to ivt ANG II were not caused by leakage of ANG II into the periphery, because plasma concentrations of ANG II did not change from control (31 +/- 7 pg/ml) at the highest dose of ANG II infused. In contrast, intravenous (iv) ANG II, 10 and 50 ng.kg-1.min-1, increased arterial pressure 29 and 47 mmHg, respectively (P less than 0.05), and decreased heart rate. ANG II, 10 ng.kg-1.min-1 iv, increased plasma ANG II levels from 36 +/- 6 to 354 +/- 69 pg/ml (P less than 0.05). Intracarotid (ic) ANG II, 10 ng.kg-1.min-1, increased arterial pressure 31 mmHg (P less than 0.05) but did not alter heart rate. ANG II ivt caused a dose-related drinking response, with a positive correlation between the amount of water drunk during ivt ANG II infusion and the increase in arterial pressure. Infusions of ANG II at 50 ng.kg-1.min-1 ivt were associated with decreased plasma osmolality and potassium concentration and increased plasma vasopressin concentration.
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PMID:Hemodynamic and behavioral effects of angiotensin II in conscious sheep. 233

With regard to the concept of the local action of the renin angiotensin system (RAS) involved in blood pressure regulation, the presence of angiotensin converting enzyme (ACE) in a variety of organs suggests that locally produced angiotensin II (ANG II) shares, at least to some extent, the actions of this peptide on respective target organs of ANG II. However, renal ACE is less well understood for its relationship between blood pressure and enzyme activity. In our present studies, with a single oral administration of enalapril to spontaneously hypertensive rats, the inhibition of renal cortical and aortic ACE, but not plasma ACE, coincided with a reduction in blood pressure. Development of high blood pressure in stroke-prone, spontaneously hypertensive rats (SHRSP) from 7 to 22 weeks of age was accompanied by an increase in ACE activity in the renal cortex. Aortic and pulmonary ACE also tended to increase with age, but was less prominent. Isolated brush-border membranes contained abundant ACE, both in Wistar-Kyoto rats and SHRSP, and the levels of ACE in renal cortical homogenates closely correlated to the levels of brush-border ACE. Thus, changes in renal cortical ACE activity in response to the ACE inhibition and in cases of SHRSP in relation to aging are apparently associated with changes in blood pressure. It is likely that renal cortical ACE activity reflects the enzyme activity in the brush borders. Thus, brush-border ACE should probably be taken into account when discussing possible roles of renal ACE.
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PMID:Angiotensin converting enzyme (ACE) in the kidney: contribution to blood pressure regulation and possible role of brush-border ACE. 243 95

The interaction of the converting enzyme inhibitor (CEI) ramipril with sympathetic neurotransmission and the baroreceptor reflex (BRR) was investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto (WKY) controls. Intravenous (i.v.) injection of ramipril (100 micrograms) attenuated the pressor responses to i.v. noradrenaline (NA) in SHRSP and WKY rats. Ganglionic blockade was performed with pentolinium (10 mg/kg i.v.), and blood pressure (BP) was subsequently supported with i.v. NA (1 microgram/min), angiotensin II (ANG II, 500 ng/min), or NA plus a subpressor dose (0.1 ng/min) of ANG II. Intravenous injection of ramiprilat (100 micrograms) significantly decreased NA-supported BP in SHRSP and WKY rats for more than 30 min, but did not lower BP in rats supported with ANG II or with NA plus a subpressor dose of ANG II. In SHRSP and WKY rats pretreated intracerebroventricularly (i.c.v.) with ramiprilat (0.5 microgram/min for 30 min), the slope of the BRR curve between increases in systolic BP and prolongation in pulse interval following bolus i.v. injections of methoxamine (10-100 micrograms/kg) was steeper than in vehicle-pretreated controls. In contrast, i.v. pretreatment with the same dose of the CEI did not increase BRR sensitivity. Our data in conscious animals demonstrate that CEI can interfere acutely with the autonomic nervous system through postsynaptic inhibition of neurotransmission and sensitization of the baroreceptor reflex. The relevance of this mechanisms for the chronic antihypertensive actions of CEI remains to be established.
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PMID:Interference with the autonomic nervous system by the converting enzyme inhibitor ramipril in conscious spontaneously hypertensive rats. 248 46

The sequential effects of an increased daily NaCl intake on hemodynamics, fluid electrolyte balances, and hormonal responses were evaluated in dogs (n = 7) with fixed circulating levels of angiotensin II (ANG II). During the control period, ANG II was infused at 3 ng.kg-1.min-1 while dogs were maintained on an 8 meq NaCl/day diet. Water intake was fixed at 700 ml/day. Continuously recorded (24 h/day) changes of total body weight (TBW) were used as an index of total body water. Cardiac stroke volume and arterial pressure were recorded, and each beat was digitized to provide hourly and 24-h average cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR). After three stable control days, daily salt intake was increased to 120 meq for 7 days. TBW increased gradually to 448 +/- 111 g (2.9%, P less than 0.05) above control by day 3. An 11% expansion of blood volume (P less than 0.05) was found (51CR-labeled red blood cells) on day 2 of high NaCl. CO rose 12% and MAP 20% (P less than 0.05) in parallel with TBW by day 4. By day 7, CO remained only 5% elevated, whereas MAP had stabilized at 20% above control levels. TPR remained significantly elevated from days 3 through 7. A positive Na balance averaging 91 +/- 8 meq (P less than 0.05) occurred on day 1. Plasma Na concentration was increased 2-3 meq/l above control throughout the period of high-salt intake. Plasma renin activity and aldosterone levels decreased to nearly undetectable levels, vasopressin rose slightly, and atrial natriuretic peptide levels increased significantly. Dogs maintained at 8 meq/day NaCl during the same infusion of ANG II showed no changes in MAP, CO, TPR, or TBW. In summary, the salt-induced hypertension was consistently related to small but significant fluid retention, blood volume expansion, elevations of cardiac output, and a gradual increase in TPR.
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PMID:Hemodynamics and blood volume in angiotensin II salt-dependent hypertension in dogs. 258 96

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


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