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

Renal perfusion has been shown to be preserved or improved during treatment by tertatolol in patients with arterial hypertension. The aims of the present study were (1) to document the central and renal hemodynamic effects of tertatolol in normal subjects and (2) to look for a possible interaction between tertatolol and products of the cyclooxygenase pathway of arachidonic acid metabolism. Five mg of tertatolol, 1 g aspirin, 5 mg tertatolol together with 1 g aspirin, and placebo were administered to 8 healthy volunteers at 1 week intervals in a random order and in a double-blind fashion. Cardiac output was measured by cardiac Doppler echography and renal blood flow and glomerular filtration rate by constant infusion techniques using I123-iodohippurate and Cr51-EDTA respectively. Measurements were performed before and then successively 2 and 4 h after oral intake of drugs or placebo. Tertatolol alone or with aspirin significantly decreased heart rate and cardiac output (P less than .05) without change in blood pressure, renal blood flow or glomerular filtration rate. The renal fraction of cardiac output was increased by tertatolol alone or with aspirin (P less than .05). Either placebo or aspirin alone had no effect. Thus tertatolol redistributes cardiac output to the kidneys in normal subjects as previously reported in hypertensive patients. This favorable effect on renal hemodynamics appers unlikely to be mediated by a local release of vasodilating prostaglandins.
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PMID:Redistribution of cardiac output to the kidneys by tertatolol does not involve prostaglandins. 257 71

Endothelial cells can release substances which profoundly affect vascular tone and platelet function. The inhibitory substances include endothelium-derived relaxing factor (EDRF or nitric oxide), prostacyclin and probably an endothelium-derived hyperpolarizing factor. Endothelin is a potent vasoconstrictor peptide released from endothelial cells. Under certain conditions, the endothelium can also produce angiotensin II, thromboxane A2 and a cyclooxygenase-dependent endothelium-derived contracting factor. In normal arteries, the effects of EDRF appear to dominate. In diseased arteries, the release and action of EDRF is impaired and that of endothelium-derived contracting factors is increased. Hyperlipidaemia, atherosclerosis and hypertension reduce endothelium-dependent relaxations. Hypoxia inhibits the release of EDRF and prolonged ischaemia severely impairs the response. Regenerated endothelium at sites of mechanical injury exhibits selective defects in response to aggregating platelets. The more effective release of EDRF in arterial compared with venous bypass grafts further suggests an involvement of the factor in preventing vascular occlusion. Therapeutic interventions with specific drugs and diets can augment the impaired endothelium-dependent relaxation of diseased arteries. Thus, functional changes of the endothelium in coronary artery disease may be an important factor in the development of vasospasm, ischaemia and thrombosis.
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PMID:Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. 268 Apr 93

To clarify the role of renal prostanoid in hyperreninemia and high blood pressure in human renovascular hypertension, we measured prostaglandin E2 and renin activity in renal venous and abdominal aortic plasma before and after the intravenous administration of the cyclooxygenase inhibitor, aspirin DL-lysine. Subjects were six patients with unilateral renovascular hypertension and six with essential hypertension. In patients with renovascular hypertension, prostaglandin E2 concentration in renal venous plasma from the stenotic kidney was 9.25 +/- 1.48 pg/ml, which was significantly higher (p less than 0.01) than the concentration in the renal venous plasma from the normal kidney (4.97 +/- 1.02 pg/ml) or in the aortic plasma (2.59 +/- 0.15 pg/ml). Plasma renin activity was also higher in the renal vein of the stenotic kidney than in the other two sites. The stenotic side/normal side ratio of the renal venous prostaglandin E2 correlated significantly with a renin ratio greater than 1.5 (r = 0.8211, p less than 0.05). Intravenous injection of aspirin DL-lysine (18 mg/kg) 30 minutes later markedly suppressed prostaglandin E2 and renin levels at all sites and clearly lowered arterial blood pressure (mean: from 120 +/- 6 to 110 +/- 5 mm Hg, p less than 0.01). The reduction in blood pressure correlated significantly with the suppression of plasma renin activity in the aorta (p less than 0.05) and in the renal vein of the stenotic kidney (p less than 0.01). Conversely, in patients with essential hypertension, aspirin had little effect on renin levels and increased mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Nov
PMID:Aspirin lowers blood pressure in patients with renovascular hypertension. 268 Sep 59

Endothelin (5 nmol/kg, i.v.) caused a transient hypotension followed by a lasting hypertension in rats. However, an abrupt fall in the blood pressure was observed in most rats 6 to 30 min after the injection of endothelin and sudden death followed with lethality noted over 60 min. An abnormal electrocardiogram (ECG) (ventricular arrhythmias) was observed in rats injected with endothelin. Endothelin (i.v.) also caused sudden death in mice. Pretreatment (5 or 60 min) with specific PAF antagonists, CV-6209 (0.1-3 mg/kg, i.v.) and WEB 2086 (30 mg/kg, p.o.), and a calcium channel blocker, diltiazem (60 mg/kg, p.o.) prevented death and attenuated the ECG changes induced by endothelin, but CV-6209 did not prevent the blood pressure changes induced by endothelin. CV-6209 (0.5-3 mg/kg, i.v.), WEB 2086, diltiazem and dexamethasone (5 mg/kg, i.v.) protected mice against the death induced by endothelin. On the other hand, aspirin (cyclooxygenase inhibitor, 100 mg/kg, p.o.) did not protect mice from the death. Thus, endothelin is a highly toxic peptide with cardiotoxic effects, and PAF may be involved in the pathogenesis of the sudden death.
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PMID:Endothelin-induced sudden death and the possible involvement of platelet activating factor (PAF). 268 21

Through the release of endothelium-derived relaxing and contracting factors, the endothelium can profoundly affect local vascular tone. In hypertension and during chronic cyclosporin A therapy, morphological changes of the endothelium develop. Recent studies in isolated arteries have demonstrated that endothelium-dependent relaxations induced by a variety of substances are decreased in acute and chronic hypertension and during cyclosporin A therapy. A reduced vascular smooth muscle responsiveness to endothelium-derived relaxing factor, the release of a cyclooxygenase-dependent endothelium-derived contracting factor in some animal models of hypertension, and possibly a decreased release of EDRF under some conditions may contribute to these functional alterations. In hypertension and during cyclosporin. A therapy, functional changes of the endothelium may contribute to increased peripheral vascular resistance and to vascular damage occurring under these conditions.
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PMID:Endothelium-dependent vascular responses: effect of hypertension and cyclosporin A. 269 60

The ability of angiotensin II and arachidonic acid to release immunoreactive prostaglandins into venous and ureteral effluents of rabbit isolated perfused kidneys was examined 7 days after suprarenal aortic coarctation (SRAC) or sham operation (SHAM). Renal vascular responses to angiotensin II were significantly enhanced in SRAC and accompanied by an enhanced venous efflux of bioassayable prostaglandins. Angiotension II-induced release of immunoreactive PGE2, PGF2 alpha, 6-keto PGF1 alpha and TxB2 into the venous effluent was exaggerated in SRAC. As angiotensin II did not stimulate TxB2 efflux in the SHAM group the induction of TxB2 release by SRAC is particularly noteworthy. These changes in eicosanoid release in response to angiotensin II were not mimicked by arachidonic acid administration. These results suggest that in renovascular hypertension angiotensin II-induced prostaglandin release is primarily augmented in the vascular compartment and is consistent with the sensitivity of renal function to cyclooxygenase inhibitors in renovascular hypertension.
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PMID:Exaggerated renal thromboxane and prostaglandin release by angiotensin II in suprarenal aortic coarctation hypertension. 274 7

Intravenous injection of the complement activator, cobra venom factor (CVF), produces acute lung injury that is neutrophil-dependent and oxygen radical mediated. Using the ex vivo model of lung perfusion, the current studies were designed to measure the appearance of eicosanoids in relation to the development of pulmonary arterial hypertension and vascular permeability. Inhibitors of the cyclooxygenase and lipoxygenase pathways were also employed to assess the possible role of eicosanoids in these two functional responses. Ten minutes after infusion of CVF, when the pulmonary hypertensive changes were maximal, no increases in eicosanoids could be detected in whole lung lavage fluid (TXB2, 6-keto-PGF1 alpha, LTB4, LTC4) or plasma (TXB2, 6-keto-PGF1 alpha) and the inhibitors failed to affect the pressor response. In contrast, lung injury as defined by increased vascular permeability was temporally associated with the appearance in whole lung lavage fluid of TXB2, LTB4 and LTC4, the presence of which was blocked by the relevant inhibitors. Lung injury was attenuated by both cyclooxygenase and lipoxygenase inhibitors. This effect was not peculiar to the isolated lung model since cyclooxygenase (ibuprofen, indomethacin) and lipoxygenase (nafazatrom, U66,855) inhibitors also attenuated the CVF-induced increased vascular permeability in intact rats. These data suggest that in the model system employed eicosanoid production is linked to increases in lung vascular permeability but not to pulmonary artery hypertension.
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PMID:Eicosanoids are involved in the permeability changes but not the pulmonary hypertension after systemic activation of complement. 283 33

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

Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and -16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent.
Hypertension 1987 Jul
PMID:Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam. 288 68

We have previously reported that des-Arg9-bradykinin can relax the phenylephrine-precontracted rabbit mesenteric artery through B1 kinin receptor stimulation and the subsequent release of prostaglandins. In the present study, we have found that this relaxant response can be converted to a contractile response by the cyclooxygenase inhibitor indomethacin. Contraction was dose-dependent and was blocked by the B1 receptor antagonist [Leu8]des-Arg9-bradykinin, with a pA2 value obtained by Schild regression similar to that reported for relaxation in the absence of indomethacin. Des-Arg10-kallidin (ED50 = 5.0 +/- 0.9 X 10(-9) M) was 16 times more potent than des-Arg9-bradykinin (ED50 = 8.1 +/- 0.8 X 10(-8) M) in contracting the indomethacin-treated artery and was also blocked by [Leu8]des-Arg9-bradykinin. In contrast, only 13 out of 24 indomethacin-treated vessels contracted in response to bradykinin, which had only one tenth and one 160th the potency (ED50 = 9.9 +/- 1.8 X 10(-7) M) of des-Arg9-bradykinin and des-Arg10-kallidin, respectively. B1 kinin receptor-mediated contraction in the presence of indomethacin was unaffected by the dual cyclooxygenase-lipoxygenase inhibitor BW 755c. These results indicate that des-Arg-kinins can stimulate both relaxation and contraction of the phenylephrine-precontracted rabbit mesenteric artery through stimulation of B1 kinin receptors. The relaxation is dependent on the release of prostaglandins, while the contraction may represent a direct effect.
Hypertension 1987 Jun
PMID:Conversion of B1 kinin receptor-mediated vascular relaxation to contraction. 288 69


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