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

Polyunsaturated fatty acids of the omega-6 and the omega-3 series have been shown to lower arterial pressure in humans and in various models of experimental hypertension by uncharacterized mechanisms. The objectives of our study were to compare the antihypertensive properties of linoleic acid (omega-6 series) and of fish oil fatty acids (omega-3 series) in a model of hypertension induced by the continuous subcutaneous infusion of angiotensin II in the rat and to determine whether or not their antihypertensive effects were mediated by the biosynthesis of vasodilator prostaglandins of classes 2 or 3. Linoleic acid and fish oil fatty acids (administered by subcutaneous injections) were equally potent in reducing, by half, the rise in systolic arterial pressure induced by the chronic infusion of angiotensin II. These antihypertensive effects were observed in the absence of any significant influence of either linoleic acid or fish oil fatty acids on the systemic and the renal synthesis of PGI2 or on the renal formation of PGE2 in vivo. Indomethacin caused a profound inhibition of the biosynthesis of PGI2 but not of PGE2 and could only partially neutralize the antihypertensive effects of linoleic acid and of fish oil fatty acids. These results suggest that, in this model of angiotensin II-induced hypertension, linoleic acid and fish oil fatty acids exert equipotent antihypertensive effects which are mainly independent of the prostaglandin system.
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PMID:Antihypertensive properties of linoleic acid and fish oil omega-3 fatty acids independent of the prostaglandin system. 255 31

To determine if oxygen-derived free radicals are mediators of endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats (SHR), the mechanism of contraction to xanthine plus xanthine oxidase was studied. Rings, with and without endothelium, of thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and SHR were suspended in organ chambers for isometric tension recording. Oxygen-derived free radicals caused concentration-dependent contractions; these contractions were twice as large in the aortas of SHR than in WKY rats. Deferoxamine reversed the response to xanthine oxidase to a small relaxation. Either allopurinol, superoxide dismutase, or catalase, or the combination of superoxide dismutase plus catalase reduced the contractions. Diltiazem inhibited the response to xanthine oxidase; in contrast, phentolamine plus propranolol did not affect it. Indomethacin and meclofenamate, but not tranylcypromine or dazoxiben blocked the contractions. Endothelium-dependent contractions to acetylcholine in aortas from the SHR were not affected by deferoxamine or superoxide dismutase plus catalase. These data suggest that hydroxyl radicals cause contractions in the rat aorta, which are dependent on extracellular calcium and mediated by activation of the cyclooxygenase in the vascular smooth muscle. The augmented contractions in the hypertensive strain are due to an increased reactivity of the smooth muscle to oxygen-derived free radicals. However, the lack of effect of the scavengers on endothelium-dependent contractions to acetylcholine suggests that the endothelium-derived contracting factor is chemically different from oxygen-derived free radicals.
Hypertension 1989 Jun
PMID:Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. 256 6

To determine whether the effects of arginine vasopressin (AVP) on the renal and systemic vessels are modulated by prostaglandins (PGs), AVP (10, 20, and 50 mU/kg/min) was infused into the renal artery before and after treatment with indomethacin (8 mg/kg) in anesthetized rabbits. Arginine vasopressin elicited a dose-dependent increase in systemic arterial pressure and renal vasoconstriction. However, after cessation of the infusion, significant renal vasodilation was observed. Indomethacin potentiated the systemic and renal vasoconstrictor actions and attenuated the renal vasodilator reaction induced by AVP. These results suggest that endogenously produced PGs buffer the vasoconstrictor action of AVP, and the renal vasodilator reaction induced by AVP could be mediated through PGs. Further, to investigate whether the effects of AVP on the systemic and renal vessels are mediated by calcium ion (Ca++), the Ca++ entry blocker nifedipine was used. Intravenous administration of nifedipine (50 micrograms/kg) attenuated the systemic and renal vasoconstrictor action of AVP. The renal vasodilator reaction induced by AVP was also diminished after treatment with nifedipine. These results indicate that the systemic and renal vasoconstrictor actions of AVP are mediated through Ca++ influx into the vascular smooth muscle cells. The present study suggests that Ca++ participates in the AVP-induced vasodilator reaction, itself probably mediated by PGs.
Hypertension
PMID:Interaction of vasopressin and prostaglandins through calcium ion in the renal circulation. 257 5

The role of PGF2 alpha in circulatory shock of intestinal origin was investigated in anesthetized dogs by measuring PGF2 alpha levels in superior mesenteric vein, right ventricle, aorta, and femoral vein during superior mesenteric artery occlusion-induced shock by comparing the circulatory effects of exogenous PGF2 alpha injected into either the superior mesenteric or the femoral vein and by inhibiting of prostanoid synthesis with indomethacin. Release of the superior mesenteric artery occlusion caused a dramatic decrease in mean arterial blood pressure; an increase in mean portal venous pressure, and more than fivefold increases in plasma PGF2 alpha levels in superior mesenteric vein, right ventricle, and aorta. In spite of the decreased mean arterial blood pressure, postocclusion blood flow in the mesenteric artery did not fall below preocclusion values. Indomethacin in itself, significantly reduced plasma PGF2 alpha levels as well as intestinal blood flow and increased mean arterial blood pressure in animals without superior mesenteric artery occlusion. Furthermore, indomethacin attenuated the magnitude of postocclusion hypotension and completely prevented PGF2 alpha production during superior mesenteric artery occlusion shock. Exogenous PGF2 alpha 10 micrograms/kg injected into the superior mesenteric or femoral vein produced hypotension or hypertension, respectively. When PGF2 alpha was injected into the superior mesenteric vein, the plasma level of PGF2 alpha in the aorta was similar to that observed during superior mesenteric artery occlusion shock, whereas PGF2 alpha injected into the femoral vein gave a significantly higher concentration. Pulmonary metabolism of PGF2 alpha was significantly reduced in shock. The present results suggest that PGF2 alpha released by intestinal tissues might play an important role in shock caused by intestinal ischemia.
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PMID:Role of PGF2 alpha in the superior mesenteric artery-induced shock. 258 97

Two women with preeclampsia treated with pindolol and propranolol became profoundly hypertensive when indomethacin was added because of premature contractions. The interaction of nonsteroidal antiinflammatory agents and beta-blockers and their role in the control of blood pressure in obstetrics are discussed. Indomethacin should not be given to pregnant patients with hypertension treated with beta-blockers.
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PMID:Antagonism of antihypertensive drug therapy in pregnancy by indomethacin? 195 96

The present study was undertaken to study the mechanism of cyclosporine-induced nephrotoxicity and hypertension. Cultured rat microvascular endothelial cells were exposed to cyclosporine for up to six days at one of the following concentrations: 10, 50, 250, and 1000 ng/ml of culture medium. Cyclosporine inhibited endothelial cell replication in a dose-dependent manner; at higher concentrations (250 and 1000 ng/ml), cell replication decreased by as much as 70 to 90% of controls at four and six days post-treatment, with no evidence of increased cell death. Drug-treated endothelial cells revealed abnormal morphological changes such as formation of cytoplasmic vesicles and nucleolar changes. Prostacyclin release by endothelial cells was increased by about threefold with the addition of cyclosporine (P less than 0.01). Indomethacin significantly decreased prostacyclin release by endothelial cells in the presence or absence of cyclosporine (P less than 0.01). Our data suggest that cyclosporine-induced nephrotoxicity may be mediated, at least partly, by the inhibitory influence of cyclosporine on the regenerative response of microvascular endothelial cells to injury, and the resultant alterations in prostacyclin production by these cells.
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PMID:Cyclosporine toxicity on cultured rat microvascular endothelial cells. 265 56

The validity of using EXP6803, a nonpeptide angiotensin II (AII) receptor antagonist, and KAA8, an AII monoclonal antibody, as specific tools for studying the physiology of AII has been established previously. In this study, we used these specific probes to examine the role of blocking AII formation in the antihypertensive effect of captopril in conscious renal artery-ligated rats (RALRs), a high renin, renal hypertensive model. Mean arterial pressure and plasma renin activity in a typical group of RALRs averaged 175 +/- 5 mm Hg and 28.2 +/- 6.2 ng of angiotensin 1 per ml/hr (n = 6), respectively. The antihypertensive effect of captopril (3 mg/kg i.v.) was determined in RALRs given either EXP6803 (30 mg/kg + 2 mg/kg/min i.v.) or KAA8 (10 mg + 1 mg/min i.v. per rat) with the corresponding vehicle-treated RALRs. These doses of EXP6803 and KAA8 were very effective in blocking the pressor response to AII but not to norepinephrine or vasopressin in RALRs. Captopril decreased mean arterial pressure by 44 +/- 2 and 53 +/- 8 mm Hg in the groups treated with the vehicles of EXP6803 (n = 5) and KAA8 (n = 5), respectively. In the presence of EXP6803 (n = 5) or KAA8 (n = 5), the antihypertensive effect of captopril was almost or totally abolished. Indomethacin did not alter the antihypertensive effect of captopril. These results suggest that the antihypertensive effect of captopril in conscious RALRs is due mainly to the blockade of AII formation. Furthermore, circulating AII rather than locally formed AII appears to play a major role in maintaining hypertension in hypertension in RALRs.
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PMID:Antihypertensive mechanism of captopril in renal hypertensive rats: studies with a nonpeptide angiotensin II receptor antagonist and an angiotensin II monoclonal antibody. 266 2

Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused rat mesenteric arteries was mediated by beta-adrenergic receptor activation. However, the precise mechanism of regulation of vascular renin-angiotensin is not completely understood. In this study, we examined the effect of indomethacin and meclofenamate on immunoreactive angiotensin I (Ang I) and immunoreactive Ang II release from perfused rat hind leg vasculature to delineate the possible relevance of prostaglandins to the vascular renin-angiotensin system in vitro. We also examined the effects of isoproterenol and propranolol on the immunoreactive Ang I and II release. Isolated rat hind legs were perfused with Krebs-Ringer solution, and immunoreactive Ang I and II released into the perfusate were measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Indomethacin and meclofenamate (10(-8) to 2 X 10(-6) M) added to the perfusion medium suppressed immunoreactive Ang I and II release to similar extents in a dose-dependent manner (p less than 0.001); the maximal percent inhibition of immunoreactive Ang II release evoked by these inhibitors (2 X 10(-6) M) was 60 +/- 6% (p less than 0.001) for indomethacin and 50 +/- 4% (p less than 0.001) for meclofenamate. Isoproterenol (10(-6) M) failed to cause a change in the release of both peptides, but propranolol (10(-6) M) slightly decreased the release of immunoreactive Ang I and II by 28 +/- 4% (p less than 0.001) and 32 +/- 4% (p less than 0.001), respectively. There was a highly significant positive correlation between the released amount of immunoreactive Ang I and that of immunoreactive Ang II altered by indomethacin (r = 0.91), meclofenamate (r = 0.94), or propranolol administration (r = 0.90). These results suggest that the renin-angiotensin in the hind legs is modulated by prostaglandins and that a difference exists in the beta-adrenergic receptor-mediated release of Ang II among diverse vascular beds.
Hypertension 1988 Jul
PMID:Suppression of angiotensin II release by prostaglandin synthesis inhibitors in hind legs. 284 Mar 95

Indomethacin attenuates the antihypertensive effect of both thiazide diuretics and beta-adrenoceptor blocking drugs. The mechanisms of these interactions are poorly understood but sodium and water retention, suppression of plasma renin activity, alterations in adrenoceptor sensitivity and impaired synthesis of vasodilator prostaglandins may all contribute to this effect. Other non-steroidal anti-inflammatory drugs (NSAIDs) may share this property of indomethacin but sulindac, which is a selective inhibitor of extrarenal prostaglandin synthesis, appears not to. This may have important clinical and theoretical implications. Clinicians must beware of this potential interaction in any patient receiving treatment for hypertension. NSAIDs may also inhibit the natriuretic response to diuretics with resultant adverse effects in patients with heart failure and other forms of oedema. NSAIDs may also have adverse nephrotoxic effects which may be exacerbated by diuretic therapy.
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PMID:Interactions of NSAIDs with diuretics and beta-blockers mechanisms and clinical implications. 286 24

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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