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

Total inositol phosphate (IP) formation was measured in the aorta and femoral artery from rabbits at 1, 2, and 6 weeks after kidney wrapping, at which times the mean arterial pressures were 88 +/- 4, 96 +/- 3 and 126 +/- 7 (control = 74 +/- 3) mmHg. Noradrenaline (10(-7)-10(-4) M)-stimulated IP formation was increased in the aorta and femoral artery from hypertensive rabbits at 2 weeks (e.g., aorta noradrenaline 10(-6) M sham = 105 +/- 14%, hypertensive = 164 +/- 20% of control). In contrast, endothelin-1-stimulated IP formation was unchanged at 2 weeks. Noradrenaline-stimulated IP formation was unchanged at 1 and 6 weeks. Basal IP formation was not significantly different in normotensive and hypertensive animals. In perinephritis hypertension, there is an alteration in phosphatidylinositol metabolism in arterial smooth muscle at the time when blood pressure is rising rapidly. This alteration may affect a specific phosphatidylinositol pool that is linked to the alpha-adrenoceptor but not to the endothelin-1 receptor.
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PMID:Noradrenaline and endothelin-stimulated inositol phosphate formation in arterial smooth muscle from rabbits with perinephritis hypertension. 179 9

1. Endothelium-dependent vascular regulation was investigated in mesenteric resistance arteries of Goldblatt two kidney-one clip (2K1C) renovascular hypertensive rats. 2. Third order branches of mesenteric arteries were dissected free and mounted on glass cannulae in an organ chamber. Changes in vascular diameter were measured in pressurized and perfused arteries with a video dimension analyzer. 3. Acetylcholine evoked endothelium-dependent relaxations that were much more pronounced with intraluminal than with extraluminal application. In 2K1C rats the relaxation induced by intraluminal, but not extraluminal acetylcholine was decreased compared to normotensive Wistar Kyoto rats (WKY). Increased duration of hypertension further decreased the response to intraluminal but not extraluminal acetylcholine. 4. Endothelin-1 and noradrenaline caused contractions which were augmented by removal of the endothelium. This augmentation was reduced in 2K1C rats compared to WKY; the difference was small with noradrenaline but more pronounced with endothelin-1. 5. In arteries without endothelium the sensitivity, but not the maximal contraction to endothelin-1 was lower in 2K1C rats, while the response to noradrenaline was not different in 2K1C rats and WKY. The sensitivity to the peptide was not further affected by increasing the duration of hypertension. 6. Thus, renovascular hypertension leads to an impaired intraluminal, but not extraluminal activation of the release of endothelium-derived relaxing factor and a decreased inhibitory effect of the endothelium against endothelin-1- and noradrenaline-induced contractions in mesenteric resistance arteries. Furthermore, the sensitivity, but not the maximal response of vascular smooth muscle to endothelin-1 was reduced.
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PMID:Renovascular hypertension impairs formation of endothelium-derived relaxing factors and sensitivity to endothelin-1 in resistance arteries. 179 2

In the last few years, so many different substances produced by the endothelium have been discovered that this structure is considered today a paracrine organ. Among these substances, there are at least three with marked vascular effects: prostacyclin (PGI-2) and the endothelium-derived relaxing factor (EDRF) are vasodilators, platelet stabilizers and anti-atherogenic. On the other hand, endothelin-1 (ET-1) is a potent vasoconstrictor and probably pro-atherogenic. There are many agents that stimulate the liberation of these substances by the endothelium and most of them stimulate simultaneously the production of the three substances. Even though it is not possible yet to define the exact participation of the endothelium in the normal regulation of coronary blood flow it is highly probably that a disfunction of this structure secondary to hypercholesterolemia, hypertension, atheromatosis, diabetes and smoking may decrease the coronary reserve, induce coronary spasm and facilitates the development of atheroma.
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PMID:[Endothelium and coronary circulation]. 182 65

To determine the hemodynamic effects of endothelin-1 (ET-1) in the fetal pulmonary circulation, we studied pulmonary vascular responses to brief and prolonged intrapulmonary infusions of the peptide in nine chronically prepared late-gestation fetal sheep. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer, and a catheter placed in the LPA allowed ET-1 infusion directly into the left lung. Brief (10-min) infusions of ET-1 (12.5-100 ng/min) increased flow up to 212% of baseline without changing pulmonary artery pressure. With prolonged (120-min) infusion of ET-1 (50 ng/min), flow increased from 69 +/- 8 to 164 +/- 23 ml/min at 10 min (P less than 0.05) but then declined and was not different from baseline at 120 min. The gradient between mean pulmonary artery and aortic pressures did not change, suggesting no constriction of the ductus arteriosus. Systemic (vena caval) infusion of ET-1 (100 ng/min for 30 min) caused systemic and pulmonary hypertension, as mean pulmonary artery pressure increased from 43 +/- 1 to 51 +/- 2 mmHg (P less than 0.05) and remained elevated for 30 min after cessation of the ET-1 infusion. We conclude that intrapulmonary ET-1 is a potent fetal pulmonary vasodilator, but its dilator effect is transient during prolonged infusion. In contrast, systemic infusion causes sustained hypertension, suggesting differential effects of ET-1 on the pulmonary and systemic circulations. These findings demonstrate marked vasoactivity of ET-1 in the fetus, suggesting a potential role in the normal or abnormal transitional circulation.
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PMID:Hemodynamic effects of endothelin-1 on ovine fetal pulmonary circulation. 185 46

We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.
Hypertension 1991 Jul
PMID:Plasma immunoreactive endothelin-1 in experimental malignant hypertension. 186 Jul 18

1 We investigated the peripheral haemodynamic effects of human alpha-calcitonin gene-related peptide (CGRP) following administration of endothelin-1 or NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide production, in conscious, chronically-instrumented, Long Evans rats. 2 Infusion of endothelin-1 (3 nmol kg-1 h-1) caused hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions. Co-infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) reduced the hypertension and abolished the hindquarters vasoconstriction caused by endothelin-1 but the renal and mesenteric vasoconstrictor actions of endothelin-1 were not affected. 3 Infusion of human alpha-CGRP (15 nmol kg-1 h-1) in the presence of endothelin-1 caused hypotension and hyperaemic vasodilatation in the hindquarters; the mesenteric vasoconstrictor effects of endothelin-1 were diminished, but there was only a transient reversal of the renal vasoconstrictor effects of endothelin-1. 4 Pretreatment with the non-peptide angiotensin II receptor antagonist, DuP 753 (10 mg kg-1), caused slight hypotension associated with renal, mesenteric and hindquarters vasodilatations, but DuP 753 did not affect responses to endothelin-1 infusion. However, under these conditions co-infusion of human alpha-CGRP (15 nmol kg-1 h-1) caused a sustained reversal of the renal vasoconstrictor effects of endothelin-1. 5 These results indicate that the failure of human alpha-CGRP to cause sustained reversal of the renal vasoconstrictor effects of endothelin-1 in the absence of DuP 753 was due to activation of the reninangiotensin system (possibly as a consequence of the hypotension). 6. In the second experiment, L-NAME (l0mgkg-1) caused renal, mesenteric and hindquarters vasoconstrictions similar to those seen in the presence of endothelin-1. However, the renal vasoconstrictor effects of L-NAME were reversed completely by human alpha-CGRP (l5nmolkg- h-1), even though the latter caused hypotension comparable to that seen in the presence of endothelin-1. These results are consistent with a lack of functional activation of the renin-angiotensin system by human alpha-CGRP in the presence of L-NAME. 7. The vasoconstrictor effects of L-NAME on the hindquarters were completely reversed by infusion of human alpha-CGRP, but hindquarters flow and vascular conductance did not rise above baseline levels. Hence these results indicate the hindquarters hyperaemic vasodilator effects of human alpha-CGRP seen in the presence of endothelin-1 were contributed to by nitric oxide-mediated mechanisms.
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PMID:Haemodynamic effects of human alpha-calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-arginine methyl ester in conscious rats. 187 60

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-1 release and studied the changes of cytosolic free Ca2+ concentrations and phosphoinositide breakdown by these agonists in cultured bovine endothelial cells. Protein kinase C inhibitors (H-7, staurosporine), an intracellular Ca2+ chelator, and an inhibitor of phospholipase C (neomycin), all abolished the agonist-induced endothelin-1 release, whereas the Ca2+ channel blocker nicardipine was ineffective. Although synthetic 1,2-diglyceride (diolein) dose dependently stimulated endothelin-1 release, downregulation of protein kinase C after pretreatment with phorbol ester resulted in decreased effects to increase endothelin-1 release by the agonists. Both arginine vasopressin and angiotensin II induced immediate and transient increases in intracellular Ca2+ levels of fura-2-loaded endothelial cells as well as formation of inositol trisphosphate; the agonist-induced intracellular Ca2+ increases were not affected either by nicardipine or by chelating extracellular Ca2+. The arginine vasopressin- and angiotensin II-induced intracellular Ca2+ increases, inositol trisphosphate formation, and endothelin-1 release were completely abolished by V1-receptor antagonist and saralasin, respectively. It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells.
Hypertension 1991 Aug
PMID:Cellular mechanism of endothelin-1 release by angiotensin and vasopressin. 190 4

To evaluate the effects of endothelin-1 (ET-1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane-anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY-80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET-1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5-30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 +/- 20.6 to 59.5 +/- 30.2% (n = 32, P less than 0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp1, Ile5]-angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 micrograms/kg/min on the average), the tumor blood flow increased from 42.3 +/- 21.6 to 76.4 +/- 22.6% (n = 32, P less than 0.001), which was significantly larger than the flow after ET-1. The results indicate that hypertension induced by systemic ET-1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET-1 appears to constrict arterial vessels in the microcirculation time-dependently, while AII constricts probably only normal peripheral arterioles.
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PMID:Comparison of the effects of intravenously bolus-administered endothelin-1 and infused angiotensin II on the subcutaneous tumor blood flow in anesthetized rats. 191 32

1. Cardiovascular responses to human proendothelin [1-38], in the absence and presence of phosphoramidon, were studied in conscious Long Evans rats, chronically instrumented for the continuous recording of heart rate, systemic arterial blood pressure and renal, mesenteric and hindquarters blood flows. 2. A dose of 0.1 nmol kg-1 human proendothelin [1-38] caused a slight pressor effect (maximum 5 +/- 2 mmHg), but a clear bradycardia (maximum -29 +/- 7 beats min-1). Renal haemodynamics were unchanged but there was mesenteric vasoconstriction and a vasodilation followed by a vasoconstriction in the hindquarters. 3. A dose of 1.0 nmol kg-1 human proendothelin [1-38] caused a gradual hypertension (maximum 42 +/- 4 mmHg at 10 min) and a profound bradycardia (-149 +/- 10 beats min-1 at 30 min). There were gradual but marked, renal and hindquarters vasoconstrictions, whereas there was a substantial mesenteric vasoconstriction that was relatively rapid in onset. 4. In 2 animals, administration of human proendothelin [1-38] at a dose of 10 nmol kg-1 caused an initial hypotension followed by a rapidly-developing pressor effect; there were renal and mesenteric vasoconstrictions and vasodilatation followed by vasoconstriction in the hindquarters. These changes were very similar to those seen following injection of endothelin-1 (0.1 nmol kg-1). 5. Phosphoramidon (2 mumol kg-1) had no cardiovascular effects itself and it did not affect significantly the pressor or mesenteric vasoconstrictor effects of human proendothelin [1-38], but it reduced the bradycardia and renal and hindquarters vasoconstrictor responses. A higher dose of phosphoramidon (lOnmolkg-') caused significant attenuation of all the responses to human proendothelin [1-38], but a substantial mesenteric vasoconstrictor response still occurred under these conditions. 6 The results are consistent with the involvement of phosphoramidon-sensitive enzyme systems in the conversion of human proendothelin [1-38] to endothelin-1 in vivo. In addition, considering the different patterns of responses to human proendothelin [1-38] in the effector tissues studied (heart, and renal, mesenteric and hindquarters vascular beds), and the differential degrees of inhibition of them by phosphoramidon, it is likely that the effects of human proendothelin [1-38] were due to its local (rather than systemic) conversion to endothelin-1 by processes with differing degrees of susceptibility to phosphoramidon.
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PMID:The effects of phosphoramidon on the regional haemodynamic responses to human proendothelin [1-38] in conscious rats. 191 89

The effects of intraluminal and extraluminal endothelin-1 and its interactions with endothelium-derived relaxing factor were studied in perfused mesenteric resistance arteries of Wistar-Kyoto rats and spontaneously hypertensive rats. Changes in intraluminal diameter were recorded. In adult Wistar-Kyoto rats, but not spontaneously hypertensive rats, low concentrations of intraluminal endothelin-1 (10(-10) to 10(-9) M) caused relaxations of quiescent arteries blocked by indomethacin. After endothelial removal, intraluminal endothelin-1 evoked concentration-dependent contractions in both strains. Extraluminal endothelin-1 caused greater contractions of arteries with endothelium than intraluminal endothelin-1, and the sensitivity was lower in adult hypertensive rats; endothelial removal enhanced the contractions to extraluminal endothelin-1 to a greater extent in hypertensive than in normotensive rats. In arteries without endothelium, intraluminal and extraluminal endothelin-1 caused comparable contractions, but the sensitivity was reduced in adult but not young hypertensive as compared with normotensive rats. Both young spontaneously hypertensive and normotensive rats exhibited a high sensitivity to the peptide. In arteries precontracted with endothelin-1, endothelium-dependent relaxation to intraluminal acetylcholine was reduced in hypertensive as compared with normotensive rats, whereas relaxations to extraluminal acetylcholine were increased in hypertensive rats. Thus, endothelin-1 interacts with both vascular smooth muscle and the endothelium. The sensitivity of vascular smooth muscle to endothelin-1 is reduced in adult hypertensive rats. Intraluminal activation of the endothelium by endothelin-1 or acetylcholine is reduced in spontaneously hypertensive rats, whereas extraluminal activation causes more pronounced responses in hypertensive than in normotensive rats, suggesting a prominent dysfunction of the intraluminal surface of the endothelium in hypertension.
Hypertension 1991 Oct
PMID:Endothelin in hypertensive resistance arteries. Intraluminal and extraluminal dysfunction. 191 94


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