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

The effects of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) on phospholipase activity were studied in aortic smooth muscle cells and renal epithelial cells. When platelet-activating factor was added to cells prelabeled with [3H]arachidonic acid, it induced rapid hydrolysis of phospholipids. Up to 28% of incorporated [3H]arachidonic acid was released into the medium from both aortic and renal cells. A transient rise of diacylglycerol was also seen after the addition of platelet-activating factor to these cells. The accumulation of diacylglycerol and monoacylglycerol was relatively small when compared with the total amount of released free arachidonic acid. The amount of [3H]arachidonic acid released was comparable to the loss of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, which indicates that platelet-activating factor stimulates phospholipase A2 and C activity in aortic smooth muscle cells and renal epithelial cells. Platelet-activating factor also enhanced prostaglandin biosynthesis in these cells.
Hypertension 1986 Mar
PMID:Platelet-activating factor stimulates prostaglandin synthesis in cultured cells. 308 42

A rat aortic explant culture system was developed for the investigation of the effects of hydrocortisone (HC) and the glucocorticoid antagonist, RU486, on prostacyclin (PGI2 synthesis. HC, but not aldosterone, progesterone, 17 beta-estradiol, or testosterone, inhibited spontaneous, epinephrine-stimulated and U46619 (an analog of thromboxane A2)-stimulated PGI2 synthesis by cultured aortic explants in a concentration- and time-dependent manner. Adequate inhibition of aortic explant PGI2 synthesis by physiological concentrations of HC was achieved after an 18-h culture. An 18-h time course was employed in subsequent experiments. In contrast, HC had no effect on arachidonic acid-stimulated PGI2 synthesis. Protein synthesis inhibitors, actinomycin D and cycloheximide, had no effect on the inhibitory action of HC on epinephrine- and U46619-induced release of PGI2. They exerted a direct inhibitory effect on aortic PGI2 synthesis. Arachidonic acid stimulated PGI2 release by the explants and was unaffected either by HC or by treatment with cycloheximide or actinomycin D. RU486 blocked the inhibitory action of HC on aortic PGI2 synthesis in a dose-dependent manner. Thus, the inhibitory effect of HC on vascular PGI2 synthesis is probably mediated through an inhibition of phospholipase A2 and not cyclooxygenase or other PGI2 synthase systems; furthermore, this inhibitory effect is not dependent upon de novo protein synthesis. RU486 antagonizes the inhibitory effect of HC. The inhibition of vascular PGI2 by hydrocortisone has implications in the pathogenesis of steroid-related hypertension and atherosclerosis and the antiinflammatory effect of steroids.
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PMID:Inhibition by hydrocortisone of prostacyclin synthesis by rat aorta and its reversal with RU486. 308 61

The influence of some oral hypoglycaemic sulfonyl ureas on PGI2 release by the rat thoracic aorta in vitro was examined using reversed phase HPLC. The column (Micro Pack MCH-10) (30 cm X 4 mm) was eluted using the solvent mixture:acetonitrile:glacial acetic acid:water (23:0.1:76.9v/v/v). Preincubation of the aortae with the sulfonyl ureas (15 microM) enhanced PGI2 release. The control release (measured as 6-oxo-PGF1 alpha) was 1.15 +/- 0.1 ng/mg wet weight. This was significantly increased to 2.30 +/- 0.20, 2.50 +/- 0.30, 2.90 +/- 0.25, 2.10 +/- 0.20 and 2.40 +/- 0.30 ng/mg by glibenclamide, gliclazide, acetohexamide, glibornuride and chlorpropamide, respectively (P less than 0.01, n = 6). Mepacrine (0.5 mM) abolished both basal and stimulated release. Thus, the enhanced PGI2 release may probably involve activation of the enzyme phospholipase A2. None of the compounds affected ADP-induced rat platelet aggregation even when the platelets were preincubated for 10 min at a concentration of 100-180 microM. The enhanced release of PGI2 may help to delay the development and progression of retinopathy, nephropathy, hypertension and thrombosis in diabetic patients prone to these diseases. Furthermore, the enhanced PGI2 release may partly underly some of the previously observed and poorly explained findings following the administration of some sulfonyl ureas into mammals.
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PMID:The influence of oral hypoglycaemic sulfonyl ureas on prostacyclin release by the rat thoracic aorta. 309 69

To reveal the role of enzymes involved in PGI2 synthesis for vascular PGI2 generation in experimental hypertensive models, we defined PGI2 synthase and phospholipases activities in the aortic wall of two different experimental hypertensive rats, e.g. spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)-salt hypertensive rats. In the stage of established hypertension both of the hypertensive models had a significantly large capacity of the vascular wall to produce PGI2, as compared to respective control rats. PGI2 synthase activities in the vascular wall were significantly increased by 27% for SHR and by 80% for DOCA-salt hypertensive rats. Moreover, the enzymatic activities were closely related to the blood pressure values for both of the models. On the other hand, phospholipase C or phospholipase A2 activities were increased or unchanged in SHR, respectively, whereas both of the phospholipases were significantly decreased in DOCA-salt hypertensive rats. Thus, it is indicated that PGI2 synthase is partly responsible for the increased PGI2 generation in the vascular wall of SHR and DOCA-salt hypertensive rats, and that vascular phospholipase C is playing a more important role in providing arachidonate for PGI2 synthesis in SHR.
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PMID:Prostacyclin synthase and phospholipases in the vascular wall of experimental hypertensive rats. 312 12

This study examines the effect of dexamethasone (Dex), a phospholipase A2 inhibitor, on the reversal of 1-kidney, 1-clip (1K,1C) hypertension and the synthesis of phospholipase A2-dependent products. Male Sprague-Dawley 1K,1C hypertensive rats [blood pressure (BP) greater than 190 mmHg] were allocated to three groups: two groups were given daily oral doses of Dex (0.142 mg/kg in water) for 72 h, whereas the third group was given water only (controls). One of the Dex-treated groups was then sham unclipped (n = 9), while the other Dex-treated group (n = 8) and the control group (n = 8) were unclipped. Dex attenuated the BP fall in the unclipped (223 +/- 8-148 +/- 9 mmHg) compared with the control unclipped (226 +/- 9-114 +/- 5 mmHg) animals (P less than 0.005). Aortic 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) was reduced in unclipped Dex-treated rats (13.4 +/- 1.2 ng/mg) compared with unclipped control rats (16.3 +/- 1.4 ng/mg; P less than 0.05) but was higher than in the sham-unclipped Dex group (11.5 +/- 1.2 ng/mg; P less than 0.05). Serum thromboxane B2 (TxB2) in the unclipped Dex-treated group was lower than in the unclipped control rats (P less than 0.05) but higher than in sham-unclipped rats (P less than 0.05). Dex significantly increased urinary prostaglandin E2 (PGE2) excretion, whereas urinary 6-keto-PGF1 alpha was unaltered. After unclipping, both urinary PGE2 and 6-keto-PGF1 alpha increased significantly, although there was no obvious difference between Dex-treated and control animals. These findings demonstrate opposite effects of Dex on renal compared with extrarenal prostanoid synthesis and support the hypothesis that attenuation of aortic 6-keto-PGF1 alpha synthesis may be responsible for the smaller fall in BP after unclipping in Dex-treated rats.
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PMID:Dexamethasone attenuates reversal of hypertension in one-kidney, one-clip rats. 317 64

The purpose of this study is to examine the relationship between lipid alterations in renal membrane of SHRSP and the progress of hypertension. Phospholipase A2 activity, prostaglandin E2 synthesis, phospholipids and phospholipid fatty acids were investigated in renal cortex and medulla of male SHRSP at the ages of 5, 10, 20 and 40 weeks, and compared with age-matched Wistar-Kyoto rats (WKY). In renal membrane of SHRSP, phospholipase A2 activity enhanced and PGE2 synthesis increased both in the renal cortex and the medulla after 20 weeks of age. Phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, and arachidonate were decreased in cortex after 20 weeks and in medulla after 10 weeks. Moreover, to determine the effect of pressure load on lipid alterations, SHRSP that received an antihypertensive treatment with hydralazine or nicardipine or enalapril for 5 weeks were compared with those without treatment. Antihypertensive treatment prevented the blood pressure from rising and suppressed decreases of phospholipids and arachidonate in phospholipid. In conclusion, these results might suggest that enhanced phospholipase A2 cause by hypertension activate the arachidonic acid cascade and increase prostaglandin synthesis, which might have an homeostatic action to lower the blood pressure in SHRSP. On the other hand, decreases of phospholipids and arachidonate may provide an explanation for the membraneous structural abnormalities in SHRSP. Antihypertensive treatments prevent these alterations, though they have different actions in SHRSP.
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PMID:[Lipid alterations in renal membrane of stroke-prone spontaneously hypertensive rats (SHRSP)]. 324 Sep 23

To define the roles of vascular prostacyclin (PGI2) synthase for PGI2 generation in deoxycorticosterone acetate (DOCA)-salt hypertension, we investigated PGI2 synthase, phospholipase A2 and phospholipase C activities in the aortic wall of DOCA-salt prehypertensive and established hypertensive rats. Vascular PGI2 generation in the DOCA-salt hypertensive rats was increased by 91%, and was associated with an 88% increase in PGI2 synthase activity and lowered phospholipase C and A2 activity. In the prehypertensive stage, DOCA-salt rats showed reduced vascular PGI2 generation. Prostacyclin synthase activity was equal to that of controls. These data clearly suggest that DOCA-salt hypertensive rats increase their vascular PGI2 generation when they develop hypertension, and that this may be due to the activation of vascular PGI2 synthase.
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PMID:Alterations to the vascular vasodepressor prostaglandin system in DOCA-salt hypertensive rats and their enzymatic analysis. 324 Dec 24

Phospholipase A2 activity and prostaglandin synthesis were studied in the renal cortex and medulla of stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar-Kyoto rats (WKY) aged 10-50 weeks. Enhanced phospholipase A2 activity was found in both the cortical and the medullary microsomes of SHRSP kidneys. Phospholipase A2 activity progressively increased with age in SHRSP, but not in WKY. Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) were the major prostaglandins found in the cortex, and PGE2 was the major prostaglandin found in the medulla. Prostaglandin l2 (PGI2) was synthesized in both the cortex and medulla, but cortical PGI2 synthesis was much lower than medullary synthesis. Enzymatic activity for all prostaglandin syntheses analysed here were higher in SHRSP. There was a greater age-related increase in prostaglandin synthesis in SHRSP kidneys than in WKY kidneys. In addition, the ratios of PGE2/TXB2 and 6-keto-prostaglandin F1 alpha (PGF1 alpha)/thromboxane B2 (TXB2) decreased in SHRSP. This may produce vasoconstriction and increase vascular resistance in SHRSP. These data suggest that increased prostaglandin synthesis and phospholipase A2 activity have an important role in the development and maintenance of hypertension in SHRSP.
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PMID:Renal prostaglandins and phospholipase A2 in spontaneously hypertensive rats. 330 39

To explore the roles of vascular phospholipase C activity in the development of hypertension, phospholipase C activity was examined in the aortic wall of spontaneously hypertensive rats (SHR). Phospholipase C activity was significantly enhanced (+87%, p less than 0.005) in 14-week-old SHR as compared with normotensive Wistar-Kyoto rats (WKY). The enzymatic activities were positively correlated with the levels of blood pressure in both of the rat strains (r = 0.62, p less than 0.003). Vascular phospholipase C was also significantly activated (+62%; p less than 0.006) in the aortic wall of 4-week-old prehypertensive SHR, as compared with age-matched WKY. In contrast, vascular phospholipase A2 activity was unaffected in the aortic wall of either adult or very young SHR. There was no difference in the cardiac phospholipase C activity between adult SHR and WKY. The vascular phospholipase C of SHR had a lower Michaelis constant (Km) value than that of WKY. Moreover, its pH profile and calcium requirement differed in part from those of WKY. These results indicate that the activation of vascular phospholipase C precedes the development of hypertension and that the enhancement may be induced by both quantitative and qualitative changes in phospholipase C in SHR.
Hypertension 1988 Jan
PMID:Enhanced phospholipase C activity in the vascular wall of spontaneously hypertensive rats. 333 38

Plasma renin activity and aldosterone concentrations were measured simultaneously with urinary excretion of kallikrein and four prostaglandins (PGE2, PGF2 alpha, 6 keto PFG1 alpha and TXB2) in 23 patients with pregnancy induced hypertension (17 with permanent PIH and six with labile PIH, since in these latter their hypertension was controlled only by home bed rest) and in 16 normotensive pregnant women at the same stage of gestation (31 +/- 3 weeks). PRA was lower in permanent PIH than in controls and in labile PIH. No difference between the three groups was observed for plasma aldosterone and the urinary excretion of kallikrein and of the prostaglandins except that TXB2 was higher in labile PIH than in permanent PIH. Correlation studies of kallikrein disclosed correlations with most prostaglandin excretions, explained by the physiological stimulation of phospholipase A2 by kallidin. Correlation studies of PRA disclosed unexpected negative correlation with PGE2 and 6 keto PGF1 alpha in the permanent PIH group. In conclusion, labile PIH has a different biological profile than permanent PIH since they have higher PRA and higher TXB2 excretion, an association which suggests a more pronounced ureteral compression by the gravid uterus in this group. Permanent PIH has a disregulation of the renin angiotensin-prostacyclin loop since PRA and 6 keto PGF1 are negatively correlated. This suggests the role of an independent vasopressive substance which would stimulate PGI2 and suppress renin secretion.
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PMID:Renin angiotensin aldosterone system, urinary prostaglandins and kallikrein in pregnancy induced hypertension. Evidence for a disregulation of the renin-angiotensin-prostacyclin loop. 384 87


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