Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.
Hypertension 1990 May
PMID:Plasma endothelin levels in hypertension and chronic renal failure. 218 51

The present study was designed to determine whether endothelin and "big endothelin" are released from aortic strips with endothelium and to examine the effect of thrombin by using a specific radioimmunoassay. Porcine aortic strips with endothelium released immunoreactive endothelin (ir-endothelin) and immunoreactive big endothelin (ir-big endothelin) into the medium in a time-dependent manner. These releases were markedly inhibited by 10 micrograms/ml cycloheximide. Expectedly, after removal of endothelium, aortic strips did not release a detectable amount of ir-endothelin and ir-big endothelin. In contrast, thrombin (10 units/ml) significantly stimulated the release of ir-endothelin and ir-big endothelin. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay revealed that the major component of ir-endothelin corresponds to standard endothelin-1 (1-21) and the major component of ir-big endothelin corresponds to standard big endothelin (porcine, 1-39). These results suggest that aortic strips with endothelium release endothelin and big endothelin slowly but continuously into the extracellular space and that these releases can be stimulated by thrombin.
Hypertension 1990 Jun
PMID:Release of immunoreactive endothelin from porcine aortic strips. 219 Sep 22

Endothelin, a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, was chronically infused into male Sprague-Dawley rats to determine whether a long-term increase in circulating endothelin levels would cause a sustained elevation in mean arterial pressure. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6 meq/day sodium intake throughout the experiment with daily measurements including mean arterial pressure, heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, cardiac output, total peripheral resistance, and stroke volume. Infusion of endothelin-1 (ET-1) at rates of 3, 5, or 7.5 pmol/kg/min for 7 days was associated with significant, sustained, and dose-dependent increases in mean arterial pressure and smaller less consistent elevations in total peripheral resistance. Other parameters were unaffected. Similar results were observed in rats receiving endothelin-3 (ET-3), except that a higher dose of ET-3 was required. These results indicate that elevated blood levels of endothelin could produce a maintained hypertension without sodium or water retention and that the hemodynamic basis for the increased mean arterial pressure is similar to that seen in most other forms of experimental and clinical hypertension.
Hypertension 1990 Jun
PMID:Chronic hypertension produced by infusion of endothelin in rats. 219 Sep 24

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The vasoconstrictor responses to periarterial sympathetic nerve stimulation and exogenous norepinephrine were determined. Infusion of endothelin-1 increased the baseline perfusion pressure dose dependently to similar extents in the two strains. A subpressor dose of endothelin-1 (10(-10) M) enhanced the pressor response to norepinephrine; its effect was greater in WKY rats than in SHR. Endothelin-1 (10(-12) to 10(-10) M) attenuated the pressor response to sympathetic nerve stimulation, and the degree of inhibition tended to be less in SHR than in WKY rats. Higher doses (3 x 10(-10) and 10(-9) M) of endothelin-1 enhanced the pressor response to nerve stimulation in both WKY rats and SHR. Endothelin-1 inhibited norepinephrine release from rat mesenteric arteries; the inhibition was significantly less in SHR than in WKY rats. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines, whereas it inhibits presynaptic adrenergic neurotransmission. Thus, endothelin can interact with the neuroeffector junction in addition to having a vasoconstricting effect in peripheral vessels. The difference in the mode of modulation by endothelin at the vascular neuroeffector junction in SHR from that in WKY rats might explain the maintenance of hypertension.
Hypertension 1990 Jun
PMID:Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats. 219 Sep 26

The interaction of the vasoconstrictor peptide, endothelin-1 (ET-1), and the endothelium-derived vasodilator eicosanoid, prostacyclin, was examined as it pertains to the modulation of gastric mucosal integrity. Using an ex vivo chamber preparation of the rat stomach, the effects of intravenous ET-1 on the susceptibility of the mucosa to damage induced by topical application of an irritant, 20% ethanol, were examined. ET-1 significantly augmented gastric hemorrhagic damage induced by the irritant when administered at concentrations in the 10(-7) to 10(-6) M range. Pretreatment with indomethacin at a dose that inhibited gastric prostacyclin synthesis by over 85% resulted in significant augmentation of the ulcerogenic actions of ET-1. The damaging actions of ET-1 could be significantly reduced by topical pretreatment of the gastric mucosa with prostacyclin (5-50 micrograms/ml). This pretreatment also significantly reduced the hypertension and hemoconcentration observed following ET-1 administration. ET-1 also significantly augmented the susceptibility of the gastric mucosa to injury induced by hydrochloric acid. Oral administration of 150 mM HCl produced little or no gastric damage in control rats. However, a 5-min intravenous infusion of ET-1 produced significant increases in the severity of acid-induced gastric damage in a concentration-dependent manner (10(-7) to 10(-6) M). These results demonstrate that ET-1 is a potent ulcerogenic agent in the rat stomach. The ulcerogenic actions of ET-1 can be significantly reduced by prostacyclin, suggesting that the balance between endothelial cell release of ET-1 and prostacyclin may be an important factor in modulating gastric mucosal integrity.
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PMID:The modulation of gastric mucosal integrity by endothelin-1 and prostacyclin. 247 84

Regional hemodynamic measurements were made in conscious, unrestrained, Wistar rats chronically instrumented with pulsed Doppler flow probes around left renal and superior mesenteric arteries and the distal abdominal aorta, or around left and right common carotid arteries. The cardiovascular changes with i.v. bolus doses (0.004 and 0.04 nmol) or a 20-min infusion (0.04 nmol/20 min of endothelin-1 (ET-1) were assessed. ET-1 at a dose of 0.004 nmol had no effect on mean arterial pressure (MAP), but caused reductions in renal and mesenteric blood flow accompanied by hindquarters hyperemia; there were no changes in carotid hemodynamics. The higher bolus dose (0.04 nmol) of ET-1 caused initial hypotension and tachycardia followed by hypertension and bradycardia; these changes were associated with sustained reductions in renal and mesenteric flows but a transient hindquarters hyperemia. There was an initial carotid hyperemia followed by a marked reduction in blood flow. Infusion of ET-1 caused progressive bradycardia and hypertension accompanied by reductions in renal and mesenteric flows, but no changes in hindquarters or carotid hemodynamics. These observations are consistent with the hyperemia in the latter vascular beds with high bolus doses of ET-1 due to release of an endogenous vasodilator substance(s).
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PMID:Regional hemodynamic effects of endothelin-1 in conscious, unrestrained, Wistar rats. 247 11

The effect of endothelin-1 on the phosphoinositide pathway was studied in slices of atria and mesenteric artery from normotensive and hypertensive (DOCA-salt) rats. Endothelin-1 induced a dose-dependent increase in inositol monophosphate production in both groups, but the reactivity of the phosphoinositide pathway was enhanced in DOCA-salt hypertensive rats. Endothelin-1 was more potent than noradrenaline and activation by these two agonists combined was additive. The phosphoinositide activation induced by endothelin-1 was independent of extracellular calcium, and was not prevented by nifedipine treatment or by removing calcium from the incubation medium. Endothelin-1 is a potent direct activator of the phosphoinositide pathway in cardiovascular tissues, and this effect is potentiated in DOCA-salt hypertension.
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PMID:Potentiated endothelin-1-induced phosphoinositide hydrolysis in atria and mesenteric artery of DOCA-salt hypertensive rats. 256 Nov 34

The effects of systemic administration of endothelin-1 and endothelin-3 on the susceptibility of the stomach to injury were compared in the anesthetized rat, as were their effects on gastric vascular tone, systemic blood pressure and hematocrit. When infused at concentrations in the 10(-7)-10(-6) M range, endothelin-1 was a far more potent hypertensive agent than endothelin-3. Endothelin-1 caused significant hemoconcentration, while endothelin-3 did not Endothelin-1 was approximately 5- to 10-times more potent as a vasoconstrictor in the stomach and a similar difference in potencies was observed when the ability of these peptides to increase the susceptibility of the stomach to ethanol-induced damage was compared. The two peptides were equipotent in producing gastric mucosal hemorrhage in the absence of any exogenous irritant. These results demonstrate that like endothelin-1, endothelin-3 has ulcerogenic and vasoconstriction actions in the stomach. While there are very large differences in the potencies of the two peptides in terms of producing systemic hypertension and hemoconcentration, the differences in the potency of the gastric ulcerogenic and vasoconstrictor effects are much less marked.
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PMID:Comparison of the effects of endothelin-1 and endothelin-3 on the rat stomach. 267 3

The mechanism of hypertension induced by recombinant human erythropoietin (rHuEPO) is unclear but may include an increase in peripheral vascular resistance. We studied changes of arterial pressure and plasma endothelin in nine consecutive hemodialysis patients before, and 6 and 12 weeks after, starting rHuEPO. In six patients, changes in cardiac index (CI), stroke index (SI) and total peripheral resistance index (TPRI) were measured by bioimpedance, and forearm vascular responsiveness to intra-arterial norepinephrine (30 to 240 pmol/min) and endothelin-1 (5 pmol/min) were assessed. Six healthy age and sex matched subjects also underwent assessment of forearm vascular responsiveness to norepinephrine and endothelin-1. Treatment with rHuEPO significantly increased hemoglobin and mean arterial pressure (MAP). TPRI also increased by 35 +/- 11%. Plasma endothelin, although elevated basally, remained unchanged. Intra-arterial infusion of norepinephrine caused a maximal increase in forearm vascular resistance (FVR) of 17 +/- 9% before rHuEPO, significantly less than the 32 +/- 5% increase in healthy control subjects (P = 0.04). The response increased to 65 +/- 15% (P = 0.03) after 12 weeks rHuEPO treatment (P = 0.51 vs. controls). Endothelin-1 caused a maximal increase of FVR at 60 minutes of 45 +/- 24% before rHuEPO, which was not significantly different from controls, and tended to decrease with rHuEPO therapy. The response to endothelin-1, but not norepinephrine, correlated inversely with MAP (r = -0.52; P = 0.03) and TPRI (r = -0.51; P = 0.04). In conclusion, these studies show that anemia in chronic renal failure is associated with depressed vascular responsiveness to norepinephrine which is restored by rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure. 747 68

A role for endothelin in malignant phase hypertension has been suggested on the basis of reported increases of circulating plasma immunoreactive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontaneous onset malignant hypertension has been described. Expression of the three genes endothelin-1, endothelin-2, and endothelin-3 was quantified in the kidney by specific RNase protection assays in rats with established malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and in normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were significantly elevated in the group with malignant hypertension compared with the other three groups. For determination of whether endothelin-1-mediated effects were crucial in the transition from benign to malignant phase hypertension, an oral nonspecific combined endothelin-A and endothelin-B receptor antagonist (bosentan) was given to hypertensive rats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conclusion, although increased endothelin-1 mRNA expression was found in kidney tissue from rats developing malignant hypertension, blockade of endothelin-1-mediated effects did not prevent the transition from benign phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a causative role and may simply reflect cellular damage and ischemia.
Hypertension 1995 Dec
PMID:Endothelin in the kidney in malignant phase hypertension. 749 Jan 50


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