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

An assay method has been developed to measure phospholipase A2 (PLA2) in ratserum and to study the possible role of this enzyme in experimental hypertension. Experiments with rat serum following 48 h of bilateral nephrectomy indicated a decrease inPLA2 activity, suggesting that kidneys might be playing an important role in regulating serum PLA2 activity and that kidneys might be a source of this enzyme. Experiments with renal hypertensive rats, spontaneously hypertensive rats, and rats receiving a low-salt diet demonstrated that a decrease in PLA2 activity was found only in those conditions in which elevated plasma renin activity was accompanied by elevated blood pressure. When elevated plasma renin activity was not accompanied by elevated blood pressure, serum PLA2 activity was unchanged. These observations represent the first biochemical separation between conditions of elevated plasma renin activity without an increase in blood pressure and conditions of elevated plasma renin activity with an increasein blood pressure.
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PMID:Phospholipase A2 in experimental hypertension. 23 1

Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension.
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PMID:The renal dopamine receptors. 162 51

To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP.
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PMID:Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke-prone spontaneously hypertensive rats. 188 28

Prostacyclin (PGI2) synthase is one of the key enzymes for vasodepressor PGI2 biosynthesis in the vascular wall. In this study, we attempted to define the alterations in PGI2 synthase and its role in the PGI2 generation in the vascular wall of deoxycorticosterone acetate (DOCA)-salt rats. The PGI2-generating capacity was enhanced significantly when DOCA-salt rats established hypertension, whereas the generation of other arachidonate metabolites, eg, PGE2, PGF2 alpha, and thromboxane, was unaltered. Moreover, the increase in PGI2 generation was associated with an increase in PGI2 synthase activity in the vascular wall. Indeed, the averaged PGI2 generating capacity was closely correlated to the averaged PGI2 synthase activity in DOCA-salt hypertensive rats and three lines of control rats. Incontrast, phospholipase C and phospholipase A2, both of which liberate arachidonate for PGI2 synthesis, were rather lowered in DOCA-salt hypertensive rats. These data clearly indicate that vascular PGI2 generation is increased in the development of DOCA-salt hypertension and that PGI2 synthase is mainly responsible for this enhancement. The increased PGI2 synthase may be relevant to the blood pressure elevation and is expected to have beneficial effects on the vascular protection in hypertension.
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PMID:Possible role of prostacyclin synthase in altered prostacyclin generation in DOCA-salt hypertensive rats. 193 Aug 48

We investigated the alterations of phospholipase C activity in the kidney and arterial wall of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Neither DOCA nor salt administration alone affected phospholipase C activity in the kidney and arterial wall. In contrast, when the rats were given both DOCA and salt and developed high blood pressure, the phospholipase C activity became greater in the outer and inner medulla (papilla) while the enzyme activity was reduced significantly in the renal cortex and arterial wall. Such an increase in phospholipase C activity was not observed in the kidney of a genetic rat for spontaneous hypertension. Moreover, the phospholipase A2 activity was also stimulated in the renal medulla of DOCA-salt hypertensive rats. Thus, these data indicate that DOCA-salt hypertension is associated with an increase in phospholipase C activity in the renal medulla, which seems primary to the development of DOCA-salt hypertension.
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PMID:Altered phospholipase C activity in renal medulla of DOCA-salt hypertensive rats. 206 2

A good model of adult respiratory distress syndrome is lung injury induced by phorbol myristate acetate (PMA). In the present study we examined the effect of mepacrine, an inhibitor of phospholipase A2, on lung injury induced by PMA in isolated blood-perfused rat lungs. In the isolated lung, saline (1 ml) or mepacrine (75 microM) alone in the perfusion system did not discernibly change the pulmonary arterial pressure (PAP) and lung weight (LW). After administration of PMA (0.16 micrograms/ml), severe hypertension and lung edema developed (delta PAP = 40.1 +/- 6.0 mmHg, p less than 0.001; delta LW = 5.5 +/- 0.7 g, p less than 0.001). Whereas, the addition of mepacrine (75 microM) prevented PMA-induced lung edema and pulmonary hypertension (delta PAP = 4.7 +/- 2.2 mmHg, delta LW = 0.2 +/- 0.2 g). To further elucidate the protective mechanism of mepacrine on lung injury, a vasodilator (nitroprusside) was given to decrease PAP levels to +6 mmHg from baseline values in the PMA group, as well as in the mepacrine-pretreated PMA (MPMA) group. During a subsequent venous pressure challenge, severe lung injury developed in the PMA group (delta LW = 9.5 +/- 2.1 g, p less than 0.001). However, with the same venous pressure challenge in the MPMA the lung weight was markedly less than that of the PMA group (delta LW = 1.0 +/- 0.2 g). Histologic findings examined by light microscopy presented intraalveolar hemorrhage and fluid accumulation, disruption of vascular basements and alveolar septa, and aggregation of inflammatory cells within the parenchyma in the lungs of the PMA group. In the MPMA group there was no evidence of intraalveolar hemorrhage and alveolar fluid accumulation, however, the occasional presence of granulocytes in the parenchyma and slight interstitial edema were still observed. In addition, depressed the chemiluminescence release from PMA activated granulocytes which were in a dose-dependent manner in vitro. These observations suggest that mepacrine inhibits PMA-induced lung injury chiefly by protection of vascular permeability. The mechanism of the protection may be due to the inhibition of oxygen radicals released from activated neutrophils and the reduction of neutrophil chemotaxis.
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PMID:The protective effect of mepacrine on acute lung edema induced by phorbol myristate acetate in rats. 209

The capacity of cultured renal medullary interstitial cells derived from Dahl salt-sensitive and salt-resistant rats to synthesize prostaglandin E2 (PGE2) was compared. Basal and arginine vasopressin (AVP)-induced PGE2 production by interstitial cells from salt-resistant rats was fourfold to fivefold higher than corresponding values of those from the salt-sensitive rats. Similarly, basal and AVP-responsive release of [3H]arachidonate were twofold higher by interstitial cells from salt-resistant compared with salt-sensitive rats. Differences in PGE2 production were abolished by the calcium inophore A23187 or the addition of exogenous arachidonate. The latter findings suggested a role for altered availability of endogenous arachidonate, possibly mediated by reduced calcium-responsive lipase activity. Basal and AVP-induced increases in cytosolic free calcium concentration, assessed by the aequorin method, were significantly lower in interstitial cells from salt-sensitive versus salt-resistant rats, further supporting a possible role for altered cellular calcium homeostasis. Studies of the potential contribution of various phospholipases and of triglyceride lipase to the release of arachidonate for PGE2 synthesis in interstitial cells implicated phospholipase A2 activity as a major pathway. When assessed in vitro in cell cytosolic fractions at identical calcium concentration, phospholipase A2 activity was lower in interstitial cells from salt-sensitive versus salt-resistant rats. Thus, both reduced cytosolic free calcium and phospholipase A2 activity of interstitial cells from salt-sensitive rats may contribute to the diminished capacity of these cells to liberate endogenous arachidonate for PGE2 synthesis.
Hypertension 1990 Apr
PMID:Decreased cytosolic calcium and prostaglandin synthesis in prehypertensive rats. 210 83

Phospholipase A2 activity, phospholipids, and phospholipid fatty acids were investigated in renal membrane of male stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto rats. Renal phospholipase A2 activity increased and membranous phospholipids especially phosphatidylcholine and phosphatidylethanolamine, decreased with age in SHRSP. Arachidonate in phospholipid also decreased with age in SHRSP. To determine the effect of pressure load on the lipid alterations in renal membrane, SHRSP that received antihypertensive treatment with hydralazine, enalapril, or nicardipine for 5 weeks were compared with those without treatment. Antihypertensive treatments prevented phospholipid degradation and increased arachidonate in phospholipid relative to the control group. Phospholipase A2 activity in each group treated with antihypertensive drugs did not differ from that in the control group. These results suggest that the course of hypertension causes renal membranous phospholipid degradation and increases phospholipase A2 activity. Antihypertensive treatments may prevent these lipid alterations in SHRSP. These renal membranous structural changes may provide an explanation not only for functional abnormalities such as decreased membrane fluidity but also for the progress of hypertension.
Hypertension 1989 May
PMID:Lipid alterations in renal membrane of stoke-prone spontaneously hypertensive rats. 272 25

We tested the new radioimmunoassay method of serum phospholipase A2 (PLA2). In healthy individuals, serum PLA2 concentrations were 301 +/- 65.6 ng/dl (mean +/- SD), and in patients with acute pancreatitis, significant elevations of serum PLA2 concentrations were observed. In clinical course of acute pancreatitis, serum PLA2 was maintained high level more longer than serum amylase and elastase 1. In patients with chronic pancreatitis, serum PLA2 concentration were low at a stage of severe exocrine dysfunction, and high at a stage of acute exacerbation. In patients with pancreatic cancer, serum PLA2 concentration were changed in accord with severity of disease states. After endoscopic retrograde pancreatography, serum PLA2 levels immediately elevated significantly, and returned to basal levels 24 hours later. Serum PLA2 concentrations were within normal range in patients with other malignant tumors, diabetes mellitus, chronic liver diseases, and hypertension, whereas in patients with chronic renal failure serum PLA2 concentrations were elevated. These results suggest that measurement of serum PLA2 can be clinically useful for diagnosis of pancreatitis and monitoring of mild and severe stage of pancreatitis.
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PMID:[Clinical studies of serum phospholipase A2 immunoreactivity]. 279 50

To study the mechanism of decreased endothelium-dependent relaxations in spontaneously hypertensive rats (SHR), rings of thoracic aorta with and without endothelium were taken from age-matched male SHR and normotensive Wistar-Kyoto rats (WKY) and suspended for isometric tension recording. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR but not in those from WKY. These contractions were inhibited by atropine but not by hexamethonium and were prevented by inhibitors of phospholipase A2 or cyclooxygenase but not by inhibitors of prostacyclin synthetase, thromboxane synthetase, or leukotriene synthetase. Prostaglandin D2, E1, E2, and F2 alpha caused concentration-dependent contractions in rings without endothelium from both SHR and WKY; the responses to the highest concentration (10(-5) M) of the individual prostaglandins were comparable in both strains. Endothelium-dependent relaxations evoked by high but not by low concentrations of acetylcholine were significantly depressed in SHR as compared with those in WKY (p less than 0.05). Indomethacin normalized endothelium-dependent relaxations in SHR. Thus, acetylcholine can activate muscarinic receptors that evoke endothelium-dependent contractions in the aorta of SHR but not in that of WKY. The contraction probably is mediated by a cyclooxygenase product(s) other than prostacyclin or thromboxane A2. The reduced endothelium-dependent relaxations to acetylcholine in the SHR probably are not due to a decreased release of endothelium-derived relaxing factor(s) but to the simultaneous release of endothelium-derived contracting substance(s).
Hypertension 1986 Apr
PMID:Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. 287 25


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