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

Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate.
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PMID:Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats. 1 24

In gravid women who are destined to develop pregnancy-induced hypertension (PIH), normal pregnancy-associated refractoriness to the pressor effects of administered angiotensin II (A-II) is lost several weeks before the onset of hypertension. From a study of the determinants of A-II pressor responsiveness in normal gravid women, it appears likely that the loss of resistance to A-II is principally unrelated to plasma renin activity or to plasma A-II levels. However, it recently has been shown that the vascular refractoriness to A-II in normal women can be reduced significantly by the administration of the prostaglandin synthetase inhibitors, indomethacin or aspirin. In seven women who had developed PIH and who had lost their refractoriness to A-II, the infusion of 5alpha-pregnan-3,20-dione (5alpha-DHP) was associated with restoration of refractoriness to the pressor effects of A-II. Moreover, in five normotensive gravid women beyond 28 weeks' gestation in whom the refractoriness to A-II was reduced by the administration of indomethacin, the intravenous infusion of 5alpha-DPH was associated with restoration of refractoriness to the pressor effects of A-II. These observations are consistent with the view that a progesterone metabolite(s) may be important in the maintenance of normal blood pressure during human pregnancy.
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PMID:Modification of vascular responsiveness to angiotensin II in pregnant women by intravenously infused 5alpha-dihydroprogesterone. 9 97

Pregnant women destined to develop pregnancy-induced hypertension (PIH) lose refractoriness to the pressor effects of infused angiotensin II (A-II) several weeks before the onset of hypertension. This loss of refractoriness to A-II is unrelated to plasma renin activity or circulating levels of A-II. In animal studies it has been shown that the prostaglandins are important mediators of vascular reactivity. Specifically, the uterine blood flow appears to vary directly with prostaglandin E concentrations in uterine venous effluent. The present study was designed to evaluate the effects of prostaglandin synthetase inhibitors on the pressor effects of A-II in human pregnancy. The "effective A-II pressor dose" (nanograms of A-II X kg-1 X min-1 necessary to cause a 20 mm Hg rise in diastolic pressure) was determined in 14 pregnant women before and after treatment with either 25 mg indomethacin or 600 mg aspirin given twice, 6 h apart. The effective pressor dose required before treatment [22.7 +/- 3.4 ng X kg-1 X min-1 (mean +/- SE)] was significantly greater than that after treatment [8.7 +/- 1.2 ng X kg-1 X min-1 (P less than 0.001)]. The refractoriness to A-II observed in normal human pregnancy may be mediated in part by the action of prostaglandins or related substances produced in the arteriole.
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PMID:Effect of prostaglandin synthetase inhibitors on pressor response to angiotensin II in human pregnancy. 12 38

Normally, women become refractory to the pressor effects of infused angiotensin-II (A-II) early in pregnancy. Gravid women destined to develop pregnancy-induced hypertension (PIH) lose this refractoriness to A-II several weeks prior to the detection of hypertension. Normal pregnant women also lose their A-II refractoriness after treatment with prostaglandin synthetase inhibitors and, in this regard become similar to gravid women who are destined to develop PIH. From this observation, we have concluded that a prostaglandin(s) or a prostaglandin-related substance(s) is likely involved in the mediation of vascular reactivity to A-II during pregnancy. The present study was conducted to ascertain if control of vascular reactivity during pregnancy also involves the cyclic nucleotides. Since theophylline is known to inhibit the action of phosphodiesterase, an action that results in increased cellular levels of cyclic 3',5'-adenosine monophosphate (cAMP), we evaluated the effective pressor dose of A-II before and after the administration of theophylline to women with mild PIH who were beyond the 28th week of gestation. The effective pressor dose of A-II in these women with PIH before theophylline treatment was 7.3 +/- 1.4 ng. times kg.(-1) times min.(-1) (mean and standard error). Following treatment of these women with the equivalent of 500 mg. of theophylline daily for four days, the effective pressor dose of A-II was 16.7 +/- 3.8 ng. times kg.(-1) times min.(-1) (p less than 0.025). These findings are consistent with the view that a prostaglandin(s) synthesized in the arteriole may modulate the vascular refractoriness to A-II by altering the intracellular level of cAMP in vascular tissues.
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PMID:Oral administration of theophylline to modify pressor responsiveness to angiotensin II in women with pregnancy-induced hypertension. 21 52

Urinary Prostaglandin E2 (PGE2), a known indicator of renal production, was measured by specific radioimmunoassay in 111 normal volunteers, 85 patients with essential hypertension, 6 with renovascular hypertension, and 23 patients with primary aldosteronism. Women excreted less PGE2 than men in both normotensive and hypertensive groups. When compared to normals, essential hypertensives demonstrated significantly lower PGE2 levels, with one third excreting less than 100 ng/24 hr, values usually seen only in subjects receiving the prostaglandin synthetase inhibitor, indomethacin. Normal PGE2 was seen in patients with renovascular hypertension, and levels were uninfluenced by treatment with the converting enzyme inhibitor SQ14225, Despite normalization of blood pressure and increased plasma renin activity. Normal PGE2 was also encountered in primary aldosteronism. These data indicate that impaired renal PGE2 biosynthesis is specific for human essential hypertension, and is not secondary to the elevated blood pressure. Although PGE2 excretion tends to be lower in low-renin hypertension, a constant relationship between PGE2 and renin is not always apparent.
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PMID:Impaired renal prostaglandin E2 biosynthesis in human hypertensive states. 21 95

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.
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PMID:Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe. 43 Mar 14

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.
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PMID:Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant. 44 54

To test the hypothesis that impaired renal prostaglandin production may accompany the hypertensive state, we have measured urinary PGE2 by radioimmunoassay in 52 normotensive and 50 hypertensive subjects. PGE2 levels were lower in females, and were not affected by Na+ intake or age. Patients with essential hypertension had significantly lower PGE2, particularly those with low-renin hypertension. Forty percent of the hypertensives excreted less than 70 ng/24 hr, values never observed in normotensives except after receiving indomethacin, a well-known prostaglandin synthetase inhibitor. It appears that impaired renal prostaglandin production is commonly encountered in patients with essential hypertension, perhaps contributing to their increased renal resistance. The data further suggest a role for renal prostaglandins in the pathogenesis of low-renin hypertension.
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PMID:Impaired renal production of prostaglandin E2: a newly identified lesion in human essential hypertension. 62 70

The precise role of the kidney in spontaneous experimental hypertension is unknown. We have analyzed the rates of renal prostaglandin synthesis by utilizing a spontaneously hypertensive rat model. The synthetic rate of prostaglandin E2, prostaglandin F2alpha, and prostaglandin A2-like products was measured in vitro with renal microsomes. In the rabbit and rat there is a steep gradient of microsomal prostaglandin synthetase from papilla to cortex with highest activities in the papilla. Comparison of the activity of prostaglandin synthetase in medullary microsomes form normotensive and hypertensive rats showed accelerated synthesis in the spontaneously hypertensive rat. These differences appeared after several months of age, were statistically significant from 3 mo of age and, on the average, represented at least a twofold increase of in vitro activity. All classes of prostaglandins were involved with increased synthesis of prostaglandin E2, prostaglandin F2alpha and prostaglandin A2-like material. These data reenforce and extend previous work showing alterations of granularity and presumably prostaglandin synthesis in renal medullary intersitital cells in various experimental hypertensions. We also measured renal tissue content of prostaglandin E and prostaglandin A-prostaglandin B by radioimmunoassay. Swift and careful handling of the tissue was necessary to avoid extensive postmortem synthesis of prostaglandins. In rapidly-frozen medullary tissue only prostaglandin E was detectable in concentrations ranging from 10 to 200 pg/mg tissue. No significant differences were found in the medullary content of prostaglandin E in the control and hypertensive rats despite the increased rates of enzymatic synthesis. We conclude that renal prostaglandin synthesis is increased in renal medullary microsomes obtained from spontaneously hypertensive rat. This apparently occurs in response to the progressive development of hypertension since young animals did not show an increase Renal tissue prostaglandin E content did not increase and therefore appears to be a poor index of enhanced prostaglandin synthesis.
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PMID:Renal prostaglandin synthesis in the spontaneously hypertensive rat. 82 78

1. Renal prostaglandins act primarily as local hormones, having their effects at, or near to, sites of synthesis. PGE2 is a major determinant of renal vascular reactivity; it opposes the vasoconstrictor and natriuretic actions of pressor hormones and brakes the release of noradrenaline from adrenergic nerves. In the unanaesthetized rabbit prolonged inhibition of prostaglandin synthesis results in hypertension. In the rat, however, renal prostaglandins augment pressor stimuli. 2. Basal efflux of renal prostaglandins is positively correlated with blood flow to the inner cortex and medulla. Those stimuli which increase renal medullary blood flow do so primarily by activating prostaglandin synthetase. 3. Kinins increase prostaglandin synthesis which action modifies the renal effects of kinins. Thus, one or more renal prostaglandins contribute to the renal vasodilator action of bradykinin and mediate its effect on excretion of water as well as possibly attenuating the natriuretic action of the polypeptide. Kinins in addition to stimulating prostaglandin synthesis may determine the principal product of synthetase by regulating the enzyme PGE 9-ketoreductase, which converts PGE to PGF. The coupling of these systems within the kidney appears unique--prostaglandins mediate some of the actions of kinins and modulate others, whereas they depend on the intrarenal generation of kinins to set their level and type of activity.
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PMID:Renal prostaglandins. 82 36


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