Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence in vitro and in humans suggest that Mg2+ can alter systemic and renal vascular tone. However, the mechanism of these effects is not known. The role of vasodilator prostaglandin release and Ca2+ flux in Mg2+-induced changes in blood pressure and renal blood flow was studied in 10 normal subjects maintained on a fixed 80-mEq Na+ and K+ diet. Magnesium sulfate infused at 200 mg/hr for 3 hours reduced systolic and diastolic blood pressure within 1 hour (from 119 +/- 2 [SEM] to 109 +/- 4 mm Hg systolic; from 74 +/- 3 to 64 +/- 4 mm Hg diastolic; p less than 0.02). This hypotensive response was seen in all subjects and persisted for 3 hours. The pulse rate did not change, but renal blood flow (p-aminohippurate clearance) increased (from 902 +/- 78 to 1108 +/- 130 ml/min/1.73 m2; p less than 0.05). The Mg2+ infusion produced a significant increase in the excretion of the stable prostaglandin I2 (PGI2) metabolite 6-keto-PGF1 alpha (from 96 +/- 12 to 154 +/- 16 ng/g creatinine; p less than 0.01). In contrast, urinary PGE2 was not altered (328 +/- 75 vs 399 +/- 145 ng/g creatinine; p greater than 0.6). To evaluate the functional role of PGI2 release, the cyclooxygenase inhibitors indomethacin (75 mg) or ibuprofen (600 mg) were given before the Mg2+ infusion. Both cyclooxygenase blockers, given in doses that inhibited immunoreactive 6-keto-PGF1 alpha release, completely prevented the Mg2+-induced decline in blood pressure and increased renal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1987 Apr
PMID:Evidence that prostacyclin mediates the vascular action of magnesium in humans. 243 56

Disturbances of prostaglandin I2 (PGI2, prostacyclin) production by adipose tissue contribute to the pathogenesis of diabetic ketoacidosis and may contribute to the pathogenesis of hypertension and vascular disease. We studied the cellular basis of PGI2 production in adipose tissue, measured as release of 6-keto-PGF1 alpha in response to epinephrine. Adipocytes did not produce PGI2 when nonfat cells were removed by repeated washing. The nonadipocyte cellular constituents of adipose tissue (nonfat cells) did not produce PGI2 in the absence of adipocytes. Both adipocytes and nonfat cells were required for PGI2 production in response to epinephrine. Adipocytes pretreated with 0.2 mM aspirin to inhibit PGH synthase nevertheless promoted PGI2 production when mixed with nonfat cells. Nonfat cells preincubated with aspirin did not produce PGI2 when mixed with adipocytes. The nonfat cells converted arachidonic acid to PGI2 but adipocytes did not. Epinephrine stimulated lipolysis and PGI2 production in a dose-dependent parallel manner, but the responses were distinct above 10(-6) M. Characterization of the nonfat cells by fractionation on a Percoll density gradient followed by measurement of angiotensin-converting enzyme activity and 6-keto-PGF1 alpha production indicated that the nonfat cells were predominantly vascular endothelial cells. We conclude that catecholamine-stimulated PGI2 production in adipose tissue results from the cooperation of adipocytes and vascular endothelial cells. The adipocytes provide arachidonic acid, which is converted to PGI2 by the vascular endothelial cells. Because adipose tissue is located near blood vessels throughout the body, adipocytes may be an important source of arachidonic acid for vascular endothelial cells in various circumstances in health and disease. Our findings raise the possibility that adipocytes may, under some circumstances, release arachidonic acid into the systemic circulation where it is used by vascular endothelial cells throughout the body to produce PGI2 and other eicosanoids.
 ...
PMID:Cooperation of adipocytes and endothelial cells required for catecholamine stimulation of PGI2 production by rat adipose tissue. 250 36

The mechanism of glucocorticoid-induced hypertension is not known. Although glucocorticoids can exert an inhibitory effect on prostaglandin synthesis in vitro, their in vivo influence on this system is controversial. The goal of the present study was to determine whether dexamethasone-induced hypertension in Wistar rats is due to inhibition of the synthesis of the vasodilator prostaglandin I2 (PGI2) in vivo. Dexamethasone caused a profound reduction (7 +/- 1 versus 21 +/- 5 ng per 24 h) in the urinary excretion of PGI-M (PGI-M), a major metabolite of PGI2, and a sustained rise in systolic arterial pressure which was maximal after 5 days (144 +/- 9 versus 103 +/- 3 mmHg). A study of the metabolism of [3H]-labeled 6-oxo-PGF1 alpha and PGI2 revealed that dexamethasone exerted a dual action on the prostaglandin system in vivo: an inhibition of PGI2 biosynthesis and an alteration of its metabolism, both effects contributing to the observed reduction in urinary levels of PGI-M. Exogenous arachidonic acid induced a fourfold increase in urinary PGI-M in normal rats (from 14 +/- 3 to 61 +/- 6 ng per 24 h). Despite a large decrease upon addition of dexamethasone, urinary PGI-M remained in the high-normal range in arachidonic acid-treated rats (21 +/- 8 ng per 24 h). Arachidonic acid exerted antihypertensive effects which were marginal initially but significant in the later phase of dexamethasone-induced hypertension (124 +/- 8 versus 139 +/- 8 mmHg in arachidonic acid-treated versus control rats after 7 days of dexamethasone).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prostaglandin I2 and glucocorticoid-induced rise in arterial pressure in the rat. 250 53

In order to determine whether the increased renal biosynthesis of thromboxane A2, observed in young genetically hypertensive (LH) rats of the Lyon strain, could be involved in the development of their hypertension, 12 LH female rats were given a specific thromboxane A2 receptor antagonist, AH 23848 (Glaxo Group Research) orally (2 mg/kg twice a day) from 3 to 9 weeks of age. In addition, 12 LH and 12 normotensive (LN) rats were given vehicle only (sodium bicarbonate 8%). The thromboxane receptor antagonist AH 23848, which inhibited platelet aggregation by about 65%, did not modify the renal production of thromboxane A2, prostaglandin I2 (PGI2) or prostaglandin E2 (PGE2). It induced a progressive, potent and long lasting decrease in systolic blood pressure which was normalized in 6-, 7- and 8-week-old LH rats, thus demonstrating the involvement of thromboxane A2 in the onset of hypertension in this model. In contrast with thromboxane synthetase inhibitors, the AH 23848 antihypertensive effect persisted 1 week after the cessation of treatment, showing the superiority of thromboxane A2 receptor blockade over thromboxane synthetase inhibition.
 ...
PMID:Antihypertensive effect of thromboxane A2 receptor blockade in genetically hypertensive rats of the Lyon strain. 253 14

Treatment with a converting enzyme inhibitor has been shown to stimulate aortic prostaglandin I2 synthesis. We studied whether converting enzyme inhibitor-stimulated prostaglandin I2 synthesis might be mediated by kinins. Anesthetized male Sprague-Dawley rats were given a continuous 70-minute infusion of either saline or a kinin analogue antagonist, [DArg0-Hyp3-Thi5-DPhe7-Thi8]bradykinin, 8 micrograms/kg/min. After 10 minutes, rats were given an intravenous bolus of either vehicle or the converting enzyme inhibitor enalaprilat (30 micrograms/100 g body wt). After 70 minutes, aorta and renal cortical slices were harvested and incubated in vitro in buffer without drugs at pH 7.4, 37 degrees C for 60 minutes. The buffer was then sampled for measurement of 6-keto prostaglandin F1 alpha (an index of prostaglandin I2), prostaglandin E2, and renin release (angiotensin I generation) by radioimmunoassay. The aortic prostaglandin I2 from rats treated with converting enzyme inhibitor was significantly elevated (36.7 +/- 5.0 ng/mg dry wt/hr) compared with aorta from rats treated with either vehicle (25.6 +/- 2.2 ng/mg/hr), kinin antagonist (25.1 +/- 2.4 ng/mg/hr), or kinin antagonist plus converting enzyme inhibitor (23.0 +/- 2.0 ng/mg/hr), p less than 0.02. There were no differences in aortic prostaglandin E2, renin release, or prostaglandin E2 from renal cortical slices. Direct in vitro incubation of aorta with molar concentrations of converting enzyme inhibitor from 10(-9) to 10(-4) had no effect on prostaglandin I2. These results suggest that kinins may mediate the effect of converting enzyme inhibition on aortic prostaglandin I2 synthesis and thereby may account for part of the hemodynamic responses resulting from treatment using converting enzyme inhibitors.
Hypertension 1989 Jun
PMID:Kinin antagonist reverses converting enzyme inhibitor-stimulated vascular prostaglandin I2 synthesis. 254 21

It has long been known that increments in renal perfusion pressure can induce an elevation of urine sodium excretion without changing renal blood flow or glomerular filtration rate. The mechanism underlying this pressure-related natriuresis remains undefined, although the interest in its elucidation has been stimulated by the notion that it may constitute the central phenomenon through which the kidney regulates blood volume and, thereby, blood pressure. Recently, the use of novel experimental techniques has disclosed some important clues about changes in renal hemodynamics that, along with changes in renal humoral regulators, allow us to visualize a possible sequence of events responsible for pressure-related natriuresis. According to this hypothesis, the autoregulatory responses responsible for maintaining glomerular filtration rate are elicited in preglomerular vasculature by changes in renal perfusion pressure. These myogenic responses are coupled through Ca2+ entry in juxtaglomerular cells with inversely related changes in the release of renin and, consequently, with the amount of angiotensin II generated in renal interstitium. The release of renin from juxtaglomerular cells is modulated by the synthesis of prostaglandin I2 from the adjacent endothelial cells. Interstitial angiotensin II could influence sodium tubular reabsorption directly by stimulating sodium transport in proximal renal tubules and indirectly by altering medullary blood flow and, thereby, medullary interstitial pressure. In the renal medulla, the effects of interstitial pressure on sodium reabsorption can be amplified by the release of prostaglandin E2 from interstitial cells. A deficient regulation of this relationship could result in a shift of the pressure-natriuresis curve, leading to hypertension.
Hypertension 1988 Jun
PMID:Mechanisms underlying pressure-related natriuresis: the role of the renin-angiotensin and prostaglandin systems. State of the art lecture. 329 17

Preeclampsia is a disorder of pregnancy characterized clinically by hypertension, proteinuria, and edema and characterized pathologically in its late stages by widespread microvascular thrombi. There is evidence from a number of studies that production of prostacyclin (prostaglandin I2, PGI2), a potent vasodilator and inhibitor of platelet aggregation, is deficient in preeclamptic compared to normal pregnancy. Traditional therapy utilizes infusions of large amounts of MgSO4, but the physiologic basis for this is not clear. We studied the effect of MgSO4 on PGI2 release by cultured human umbilical vein endothelial cells (HUVEC) by several methods. By platelet aggregometry, the known antiaggregatory effect of intact HUVEC was enhanced by MgSO4. By radioimmunoassay for 6-keto-PGF1 alpha, the stable metabolite of PGI2, it was shown that MgSO4 amplifies release of PGI2 by HUVEC in a dose-dependent manner, with a peak occurring between 2 and 3 mM. In separate experiments, MgSO4 overcame the enhanced adherence of platelets to HUVEC exhausted by repeated exposure to thrombin. Finally, PGI2 production was 2- to 5-fold greater by HUVEC incubated with plasma obtained from preeclamptic patients undergoing MgSO4 therapy than by HUVEC incubated with pretherapy plasma. We conclude that MgSO4 mediates enhanced production of PGI2 by vascular endothelium, thereby potentially enhancing its thromboresistant properties.
 ...
PMID:Magnesium sulfate: rationale for its use in preeclampsia. 351 61

This study was designed to examine the effects of diets that alter prostaglandin biosynthesis on the blood pressure in one-kidney, one clip rats with established hypertension and to compare the prostanoid generating capacity of hypertensive animals with those that remained normotensive. Rats attaining blood pressures of at least 180 mm Hg within 8 weeks of nephrectomy and renal artery stenosis were paired by weight and blood pressure and then placed on either a safflower oil or a prostaglandin I2 inhibitory diet (cod liver oil-linseed oil mix) for 4 weeks. Animals with blood pressures of less than 150 mm Hg were also paired for the same two dietary regimens. Comparison between the two blood pressure groups revealed that on both dietary regimens hypertensive rats produced significantly more aortic 6-keto-prostaglandin F1 alpha and serum thromboxane B2. Rats on the cod liver oil-linseed oil diet incorporated eicosapentaenoic acid into tissue stores with a corresponding decrease in arachidonic acid and significantly impaired ability to generate serum thromboxane B2 (36%), aortic 6-keto-prostaglandin F1 alpha (65%), renal homogenate 6-keto-prostaglandin F1 alpha (64%) and prostaglandin E2 (58%), and urinary prostaglandin E2 (70%) and 6-keto-prostaglandin F1 alpha (52%). Despite these differences in prostanoid synthesizing capacity, no differences in blood pressure were observed between the safflower oil-fed rats and rats fed cod liver oil-linseed oil within either the hypertensive or normotensive groups. These results suggest that prostanoids do not play a major role in maintaining blood pressure in established one-kidney, one clip hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Changes in prostanoid synthesis in response to diet and hypertension in one-kidney, one clip rats. 390 14

The effect of prostaglandin I2 and two other vasodilator agents, acetylcholine and sodium nitroprusside, on systemic and renal circulation was studied in 29 adult euvolemic Sprague-Dawley rats. Intra-aortic infusion of prostaglandin I2 (3.6 micrograms/kg/hr; n = 6 rats) produced significant vasodilation (p less than 0.05), as indicated by an average reduction in total peripheral vascular resistance of 24.8 +/- 2.0%, while renal vascular resistance remained essentially unchanged. Essentially identical findings were obtained in a separate group of six rats pretreated with intravenous administration of saralasin (0.5 mg/kg/hr). In contrast, in another group of six rats pretreated with saralasin, intraaortic infusion of acetylcholine (0.35 mg/kg/hr), which caused a reduction in total peripheral vascular resistance (21.4 +/- 3.8%) comparable to that induced by prostaglandin I2, produced a significant fall in renal vascular resistance (average, 27.7 +/- 5.0%) and, hence, an increase in renal blood flow (average, 26.2 +/- 2.9%). The effect of sodium nitroprusside (0.4 mg/kg/hr i.v.) was intermediate between those of prostaglandin I2 and acetylcholine: both renal vascular resistance and total peripheral vascular resistance fell mildly. These results indicate that prostaglandin I2, given in a dose sufficient to cause systemic vasodilation, fails to induce any discernible renal vasodilative response and that this absence of renal vasodilation by prostaglandin I2 in vivo is not due, as previously postulated, to the highly efficient offsetting influence of intrarenal angiotensin II release.
Hypertension
PMID:In vivo influence of prostaglandin I2 on systemic and renal circulation in the rat. 390 13

Glucocorticoids have a permissive effect on vascular tone and blood pressure; they enhance vascular responsiveness to vasopressors such as catecholamines without necessarily having an effect when administered alone. This effect does not require central or systemic mediation. Prostacyclin (prostaglandin I2; PGI2), a potent vasodilator, is produced by the vascular endothelium, vascular smooth muscle cells, adipocytes, and other cells. PGI2 production by vascular endothelium and other cells is decreased by glucocorticoids. The hypothesis is proposed that the effect of glucocorticoids on vascular tone is mediated by inhibition of PGI2 production by vascular endothelium (possibly other cells also). The inhibition of PGI2 production by glucocorticoids may contribute to the hypertension of Cushing's syndrome. Loss of this inhibitory effect in glucocorticoid deficiency states (eg, Addison's disease) may cause enhanced PGI2 production, which may contribute to the haemodynamic and gastrointestinal manifestations of these disorders.
 ...
PMID:Inhibition of prostacyclin production mediates permissive effect of glucocorticoids on vascular tone. Perturbations of this mechanism contribute to pathogenesis of Cushing's syndrome and Addison's disease. 613 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>