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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although indapamide has been used for many years as a first-line treatment of hypertension, it is only recently that some of its activities on the changes of the cardiovascular system, brought on by age and high blood pressure, have been studied. Indapamide appears to reduce blood pressure by a combined diuretic and direct vascular activity reducing vascular reactivity and total peripheral resistance. In addition, it has discrete effects on a number of interrelated systems that may protect the cardiovascular system. Indapamide reduces intracellular calcium levels, maintains magnesium ions, but reduces phosphate ions that may be involved in arterial rigidity. Circulating catecholamines remain unchanged but there is a reduction in normetanephrine, suggesting a reduction in sympathetic tone. It stimulates prostacyclin synthesis, increases levels of circulating prostacyclin, reduces platelet aggregation and stimulates the vasodilation elicited by endothelium-derived relaxing factor in the presence of bradykinin. In addition, it inhibits the formation of the vasoconstrictor prostanoid, thromboxane A2. The free radical scavenging activity of indapamide could also protect the vascular smooth muscle from the reperfusion injury of cerebral and myocardial ischemia. Indapamide induces a reduction in cerebral ischemia after carotid ligation. Unlike some other antihypertensives, it does not upset the high-density/low-density lipoprotein-cholesterol balance, reducing the possible risk of atherosclerosis. Moreover, the combination of binding to elastin and reduction in uptake of calcium and phosphate into the smooth muscle could be a mechanism for reducing arterial rigidity seen in the elderly and hypertensive patient. In hypertensive patients, these properties induce an improvement in arterial compliance, and in the long term a reduction in left ventricular hypertrophy. These pharmacologic and clinical results, together with a good antihypertensive efficacy and acceptability, suggest that indapamide may be a preferential agent in the long-term cardiovascular protection of the hypertensive patient.
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PMID:Cardiovascular protective properties of indapamide. 218 50

Converting enzyme inhibitors (CEIs) are widely used in treatment of essential hypertension. Large-scale clinical studies have shown that CEIs are well tolerated and cause fewer side effects than most other antihypertensive agents. The latter observation is fundamental for compliance with long-term treatment. There do exist, however, some side effects which although rare are not negligible. It is necessary though to distinguish between side effects linked to the class of therapeutic agents and those associated with particular structural features. Three types of side effects have been seen: 1) manifestations linked to inhibition of angiotensin II with systemic vasodilation (hypotension, vertigo) and decreased glomerular pressure (functional renal impairment) with preferred onset in renovascular hypertension; 2) potentiation of the bradykinin-prostaglandin system which causes cutaneous eruptions and for reasons still poorly understood a cough which may justify discontinuance of treatment: 3) side effects for which the sulfydryl group is essentially responsible (rash, dysgeusia, neutropenia, proteinuria) and which basically appear to be linked to the use of high doses of captopril. In general terms, and bearing in mind the frequently dose-dependent character of the side effects, it is advisable to prescribe low doses of CEIs, and this therapeutic approach is strengthened by the possibility of concomitant use of a thiazide diuretic allowing improved antihypertensive effects, coupled to better reciprocal tolerance of the drugs. The end result is a better quality of life for the hypertensive subject, and hence improved compliance with long-term treatment.
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PMID:[Quality of life of patients with hypertension treated with converting enzyme inhibitors]. 218 15

The endothelium has a strategical anatomical position between the circulating blood and vascular smooth muscle cells. It has recently been recognized that endothelial cells play an important regulatory role in the circulation. The cells metabolize or activate vasoactive hormones (ie, norepinephrine, serotonin, bradykinin, angiotensin II), produce substances involved in coagulation and can release endothelium-derived relaxing factors and contracting factors. Nitric oxide and prostacyclin are vasodilators and inhibitors of platelet function. Endothelin is the most potent vasoconstrictor substance known. Thus, the endothelium can profoundly affect platelet adhesion and aggregation, vascular smooth muscle tone and possibly also vascular smooth muscle growth. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. In contrast, in hypertensive and atherosclerotic arteries the release of endothelium-derived relaxing factors and/or the responsiveness of vascular smooth muscle cells to the relaxing factors is reduced, while that of endothelium-derived contracting factors is augmented. This imbalance of endothelium-derived relaxing and contracting factors may be important in the pathogenesis of hypertension and its cardiovascular complications.
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PMID:Imbalance of endothelium-derived relaxing and contracting factors. A new concept in hypertension? 218 44

Apart from their established use in the treatment of hypertension and heart failure, ACE inhibitors have been suggested to exert anti-ischemic effects. This article reviews the mechanisms of systemic and intracardiac angiotensin formation, as well as its interaction with the bradykinin, the prostaglandin, and the sympathetic nervous system. While high doses of angiotensin can precipitate myocardial ischemia. experimental data on a potential beneficial effect of ACE inhibitors on ischemic myocardial blood flow and function are inconsistent and controversial. Pooling the few available clinical data, several ACE inhibitors may attenuate myocardial ischemia at rest and during exercise. However, a significant fraction of patients does not benefit or even deteriorates. Recent experimental studies suggest a beneficial role of ACE inhibitors in attenuating reperfusion arrhythmias and postinfarction left ventricular remodeling. Unless the mechanisms and determinants of potential anti-ischemic actions of ACE inhibitors can be better defined, their use for treatment of myocardial ischemia cannot be recommended at present.
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PMID:ACE inhibitors for the treatment of myocardial ischemia? 227 72

Increased blood pressure responsiveness to bradykinin in comparison with other vasodilator agents was demonstrated in rats with long-term one-kidney and two-kidney, one clip hypertension. In the present study, we analyzed the reactivity to intra-aortically injected bradykinin in unanesthetized one-kidney, one clip hypertensive rats during the control period and 1, 5, and 8 hours after reversal of hypertension after removal of the renal artery constriction. One and 5 hours after unclipping the renal artery, the mean blood pressure decreased markedly (from 195 +/- 7 to 124 +/- 8 and 145 +/- 9 mm Hg, respectively), whereas the hyperreactivity to bradykinin reverted only slightly, and the responses to nitroprusside remained unchanged. In another group of hypertensive rats examined 8 hours after unclipping (pressure decreased from 192 +/- 4 to 143 +/- 8 mm Hg), the hyperreactivity to bradykinin had partially reverted. Significantly larger doses of bradykinin were necessary to produce the same decrease in blood pressure when compared with the control period (16.4 +/- 2.0 vs. 7.2 +/- 1.2 ng). The same degree of reversal of hyperreactivity to bradykinin was observed when the blood pressure of hypertensive rats was reduced (from 207 +/- 8 to 143 +/- 5 mm Hg) during 1 hour by hydralazine injection. Complete reversibility of bradykinin hyperreactivity was produced by nitroprusside infusion (from 201 +/- 13 to 142 +/- 10 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Feb
PMID:Reversal of hyperreactivity to bradykinin in renal hypertensive rats. 229 70

Vasoconstriction and hypertension have been prominent during cyclosporin A (CSA) administration. To evaluate whether CSA modulates vascular responsiveness to pressor stimuli in the intact organism, CSA was administered via osmotic pump (10 and 20 mg.kg-1.day-1 ip vs. olive oil vehicle) for 2 wk. After 8 days, arterial pressure and dose-response relationships to norepinephrine, angiotensin II, and bradykinin were measured in conscious animals. Despite similar initial pressures, dose-response relationships were markedly attenuated to both norepinephrine and angiotensin II. Maximal responses were not affected, indicating a rightward shift without loss of peak effect. Vasodilation with bradykinin was not diminished. These changes were not evident after an acute CSA infusion at the same dose (10 mg.kg-1.day-1 over 2 h). Treatment with verapamil (0.505 mg/kg over 2 days) lowered basal arterial pressures but did not change the effects of CSA on pressor sensitivity. Despite attenuated pressor responses, renal vascular resistance was elevated and glomerular filtration diminished during CSA administration. These observations indicate that cyclosporin modifies vascular responsiveness to pressor stimuli in the rat and may explain the relative resistance of this species to cyclosporin-induced hypertension.
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PMID:Altered pressor responses to NE and ANG II during cyclosporin A administration to conscious rats. 231 99

The purpose of this study was to investigate the effects of chronic ethanol consumption on blood pressure and vascular responses, specifically, the possible alterations in endothelium-dependent relaxation which are associated with ethanol-induced hypertension in the rat model. Male rats received ethanol in drinking water for 13 weeks. Systolic pressure was recorded weekly. Following treatment, segments of thoracic aorta with and without intact endothelium were used to generate relaxation-response curves to the endothelium-dependent agents, acetylcholine, ATP and bradykinin, as well as the endothelium-independent agents, adenosine and sodium nitroprusside. Mean systolic pressures at the end of the treatment period were: 127.8 +/- 1.2 and 151.1 +/- 1.3 mmHg for controls and ethanol-treated rats, respectively. Ethanol treatment did not affect the relaxation produced by either acetylcholine, ATP or sodium nitroprusside in aorta with or without endothelium. In contrast, ring segments with intact endothelium from ethanol-treated rats exhibited augmented relaxation in response to both adenosine and bradykinin compared to controls. Removal of the endothelium abolished the relaxation produced by bradykinin in both groups. Although removal of the endothelium had no effect on the relaxation produced by adenosine in the control group, it attenuated the adenosine-induced relaxation in the ethanol-treated group back to control levels. These data suggest that chronic ingestion of ethanol causes elevated blood pressure and augments the endothelium-dependent relaxation to bradykinin. These findings also suggest that chronic ethanol treatment can cause the appearance of an endothelium-dependent component in the relaxation produced by adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of chronic ethanol treatment on endothelium-dependent responses in rat thoracic aorta. 232 85

The role of the renal kallikrein-kinin system in the regulation of renal function is not completely understood. Intrarenal kinins can influence renal function by acting as paracrine hormones at basolateral, luminal, or both sites in the distal nephron. To examine the role of intrarenal kinins in deoxycorticosterone acetate-salt-treated rats, which have high renal kallikrein, Fab fragments of antibradykinin antibody or DArg[Hyp3Thi5,8DPhe7]bradykinin, a kinin antagonist, were used to block kinins. At the dose used, the antibody (25 mg) and kinin antagonist (10 micrograms/min/rat) inhibited the hypotensive effect of intra-arterially injected bradykinin (100 ng) by 70% and 52%, respectively. The antibody appeared in the urine within 30 minutes after administration. Urinary volume was lowered from 9.4 +/- 0.2 to 6.7 +/- 0.4 microliters/min/g kidney wt (p less than 0.001, paired t test) by the antibody and from 8.5 +/- 0.3 to 6.8 +/- 0.4 microliters/min/g kidney wt (p less than 0.004, paired t test) by the kinin antagonist. The antibody lowered urine sodium excretion from 1.11 +/- 0.04 to 0.88 +/- 0.06 mueq/min/g kidney wt (p less than 0.001, paired t test), whereas the kinin antagonist had no significant effect. Neither altered blood pressure, renal blood flow, or glomerular filtration rate. These data suggest that in deoxycorticosterone acetate-salt-treated rats, excretion of water and sodium is regulated in part by kinins. The antidiuretic effect of the antibody and kinin antagonist might be due to blockade of kinins in the vascular-interstitial space of the kidney, since the kinin antagonist is likely hydrolyzed in the proximal tubule and does not reach the lumen of the distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Jun
PMID:Renal effects of Fab fragments of kinin antibodies on deoxycorticosterone acetate-salt-treated rats. 235 28

Captopril (0.15-10 mg/kg) administration in the anesthetized dog causes immediate hypotension concomitant with an increase in tonus of the assay tissue (cat terminal ileum) superfused with circulating blood (Vane's cascade method). The increase in cat terminal ileum tonus was antagonized by a bradykinin receptor antagonist, L-349b. Treatment of the animals with indomethacin blocked or reversed the hypotensive effect of captopril without affecting the increase in tonus of the cat terminal ileum. Captopril potentiated the hypotension induced by bradykinin injected intra-arterially, and indomethacin reduced the hypotensive effect of intra-arterially injected bradykinin. Addition of captopril or enalapril to the superfusing blood maintained at 37 degrees C in an extracorporeal circuit caused a long-lasting increase in the tonus of the cat terminal ileum. The present results support the hypothesis that immediate hypotension induced by captopril involves a prostaglandin-dependent component possibly resulting from increased bradykinin levels generated in the vicinity of captopril action.
Hypertension 1990 Feb
PMID:Hypotensive effect of captopril. Role of bradykinin and prostaglandinlike substances. 240 62

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18


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