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

Concentrations of prostaglandins E2 and I2 may be decreased in preeclamptic and eclamptic pregnancies. Because these prostaglandins produce vasodilation and inhibit platelet aggregation it has been suggested that a reduction in their biosynthesis might play an important role in the pathogenesis of the hypertension and coagulation abnormalities associated with preeclampsia. Placental tissue is an extremely rich source of several enzymes that catalyze the catabolism of prostaglandins. The present study was initiated to determine whether one of these catabolic enzymes might be increased in preeclamptic/eclamptic pregnancies. The activities of the NAD- and the NADP-linked 15-hydroxyprostaglandin dehydrogenases were measured in 16 preeclamptics (mean diastolic pressure, 108 +/- 13 mmHg) and compared with 16 normotensive controls matched for age (20.8 +/- 5.43 vs. 20.6 +/- 5.16) and gestational week of delivery (34.6 +/- 5.40 vs. 35.0 +/- 5.06). These results indicate that the activity of the placental NAD-linked 15-hydroxyprostaglandin dehydrogenase is elevated in preeclampsia (40.1 +/- 31.3 vs. 14.9 +/- 8.30 mU/g tissue, P less than 0.01). If this increase were also expressed in vivo, its effect on prostaglandin metabolism could be mistaken for impaired prostacyclin biosynthesis unless both the 6-keto- and 6,15-diketo-metabolites of prostacyclin were measured.
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PMID:In vitro activity of nicotinamide adenine dinucleotide- and nicotinamide adenine dinucleotide phosphate-linked 15-hydroxyprostaglandin dehydrogenases in placentas from normotensive and preeclamptic/eclamptic pregnancies. 330 60

This study was designed to investigate whether the hypertension produced by dexamethasone in the rat is associated with a deficit in circulating and renal prostaglandin E2 (PGE2) and PGI2, PGs that are presumed to contribute to antihypertensive mechanisms. The administration of dexamethasone (2.5 mg kg-1 week-1, sc) increased systolic blood pressure by 41 +/- 6 mm Hg (P less than 0.05) after 14 days of treatment, associated with elevations of urine volume and fluid intake and loss of body weight. The glucocorticoid, however, had no effect on the plasma concentration, urinary excretion, or vascular and renal tissue release of immunoreactive 6-keto-PGF1 alpha, a PGI2 metabolite. In contrast, dexamethasone increased (P less than 0.05) the plasma PGE2 concentration by 157% and PGE2 urinary excretion by 134% after 14 days of treatment. However, the basal release of immunoreactive PGE2 as well as the angiotension II-induced release of radiolabeled arachidonic acid and PGs from renal medulla slices incubated in Krebs solution were diminished in rats receiving dexamethasone. The steroid also reduced to about 60% (P less than 0.05) of the control value the activity in renal homogenates of 15-hydroxyprostaglandin dehydrogenase (PGDH), a major PG-catabolizing enzyme, without affecting the activity of the enzyme in the lung. Hence, the increased plasma concentration and renal excretion of PGE2 caused by dexamethasone in the face of reduced renomedullary production of the PG is presumably related to diminished degradation in the kidney and perhaps in other extrapulmonary tissues. Altogether, this study demonstrates that the hypertension induced by dexamethasone in the rat is not associated with a deficit in circulating and renal PGE2 and PGI2.
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PMID:Plasma concentrations, renal excretion, and tissue release of prostaglandins in the rat with dexamethasone-induced hypertension. 642 64

15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.
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PMID:15-Hydroxyprostaglandin dehydrogenase and hexokinase in spontaneously hypertensive rat kidney. 651 Apr 88

The effect of high salt intake on vascular and renomedullary prostaglandin (PG) synthesis was compared in Sprague-Dawley and salt-sensitive (S) and -resistant (R) Dahl rats. Animals were given a diet containing either 0.6% or 8% NaCl starting at 5 weeks of age, and were sacrificed 6 weeks later. Systolic blood pressure of S rats increased to 220 +/- 7 mm Hg but was unaffected in R and Sprague-Dawley rats. Prostaglandin synthesis was studied in aortic rings and renomedullary microsomes using 14C-arachidonate as substrate. [3H]PGE2 degradation was measured in the renocortical cytosol. In Sprague-Dawley and R rats, aortic PGI2 synthesis was not affected by high salt intake, while a significant increase compared to animals on 0.6% NaCl (from 608 +/- 84 to 992 +/-108 pmoles/60 min, p less than 0.05) was noted in S rats. Enhancement of PGI2 synthesis in S rats may be secondary to the hypertension. Salt-loading consistently stimulated renomedullary PGE2 synthesis in all three animal groups. S rats, however, had the lowest PG synthesis in renal medullas compared to Sprague-Dawley and R rats when placed on either diet. Thus, even after 6 weeks on high salt, S rats did not reach the levels of PGE2 synthesis seen in R or Sprague-Dawley rats on regular diet. The activity of cortical 15-hydroxyprostaglandin dehydrogenase was increased by salt-loading in S and Sprague-Dawley, but not in R rats. R rats had lower dehydrogenase activity than the other two groups when placed on either diet. The observed differences in PG synthesis and catabolism will tend to maintain the net output of renal PGs highest in R and lowest in S rats. These differences correlate with the reported differences in renal papillary flow between these two rat strains and may be relevant to their susceptibility or resistance to hypertension in response to salt.
Hypertension
PMID:Effect of salt on prostaglandin metabolism in hypertension-prone and -resistant Dahl rats. 721 76

Reduced renal 15-hydroxyprostaglandin dehydrogenase (PGDH) activity has been proposed as a cause, subsequent to elevation of intrarenal prostaglandin (PG) E2 levels, of the development or maintenance of high blood pressure (BP) in the New Zealand genetically hypertensive (NZGH) rat. To test this hypothesis, PGDH activity in homogenates of kidneys and lungs and in urine concentration and excretion of PGE2 were determined in male and female NZGH and normotensive control (NZNR) rats. Lung PGDH activities of the four groups were similar. Renal PGDH activity was 50% lower for the male NZGH than for the male NZNR, but for the female rats no difference in renal PGDH activity was found between NZGH and NZNR. In addition, there was a large sex-related difference in renal PGDH activities, values for the female rats being only 5% to 10% of the values for males. Urine PGE2 concentration and excretion were two to five times greater for the female rats than for the males, but did not differ between male NZGH and male NZNR. From these observations, it appears that neither renal PGDH activity nor urine PGE2 levels is associated with hypertension in the New Zealand genetically hypertensive strain of rats.
Hypertension
PMID:Renal prostaglandin excretion and metabolism in male and female New Zealand normotensive and genetically hypertensive rats. 721 80

Short-chain dehydrogenase reductase (SDR) enzymes influence mammalian reproduction, hypertension, neoplasia, and digestion. The three-dimensional structures of two members of the SDR family reveal the position of the conserved catalytic triad, a possible mechanism of keto-hydroxyl interconversion, the molecular mechanism of inhibition, and the basis for selectivity. Glycyrrhizic acid, the active ingredient in licorice, and its metabolite carbenoxolone are potent inhibitors of bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD). The three-dimensional structure of the 3 alpha,20 beta-HSD carbenoxolone complex unequivocally verifies the postulated active site of the enzyme, shows that inhibition is a result of direct competition with the substrate for binding, and provides a plausible model for the mechanism of inhibition of 11 beta-hydroxysteroid dehydrogenase and 15-hydroxyprostaglandin dehydrogenase by carbenoxolone. The structure of human 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD) suggests the details of binding of estrone and 17 beta-estradiol in the active site of the enzyme and the possible roles of various amino acids in the catalytic cleft. The SDR family includes over 50 proteins from human, mammalian, insect, and bacterial sources. Only five residues are conserved in all members of the family, including the YXXXK sequence. X-ray crystal structures of five members of the family have been completed. When the alpha-carbon backbone of the cofactor binding domains of the five structures are superimposed, the conserved residues are at the core of the structure and in the cofactor binding domain, but not in the substrate binding pocket.
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PMID:Structure and function of steroid dehydrogenases involved in hypertension, fertility, and cancer. 902 22

Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal diet upon prostaglandin metabolism. Pregnant rats were fed isoenergetic diets containing 18% casein (control) or 9% casein (low protein) from conception until littering. The offspring of these pregnancies were studied at day 20 of gestation, full-term gestation and at 4, 7 or 12 weeks postnatal age. Prostaglandin E(2) concentrations in plasma were similar in control and low-protein diet-exposed rats at 4 weeks of age. Urinary prostaglandin E(2) excretion was, however, significantly increased by prenatal undernutrition in rats at both 4 and 12 weeks postnatal age. The principal enzyme of prostaglandin E(2) degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH) exhibited significantly lower activity in the kidneys of 4-week-old rats exposed to a maternal low-protein diet. This effect was transient and absent by 12 weeks postnatal age. There was also some evidence of an altered developmental profile of PGDH activity in the lungs of low-protein diet-exposed rats. These data are consistent with the long-term programming effects of the maternal diet upon renal prostaglandin metabolism. In the rat, increased local prostaglandin E(2) concentrations associated with impaired degradation may contribute to increased renovascular resistance and hypertension.
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PMID:Long-term modification of the excretion of prostaglandin E(2) by fetal exposure to a maternal low protein diet in the rat. 1043 8

We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin.
Hypertension 2016 08
PMID:Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice. 2729 92