Effect of endothelin-1 in man.

Abstract

The effect of an intravenous infusion of human endothelin-1 on blood pressure and plasma concentrations of endothelin-1, potassium, sodium, renin, aldosterone, and atrial natriuretic factor was investigated in six healthy, sodium-loaded men. During the peptide's exogenous application (1.0, 2.5, and 5.0 ng/kg* min), its plasma concentrations rose from a basal value of 1.2+0.3 to 3.2+1.9, 9.9±7.6, and 56.5±50.3 pmol/l (p<0. medication was permitted for at least 4 weeks before the study. All subjects were fasting overnight, and alcoholic beverages, coffee, and cigarette smoking were discontinued for at least 12 hours. On the day of the study, the subjects were in the supine position for at least 2 hours. Indwelling catheters were inserted into an antecubital vein of each arm -one for infusion and the other for blood sampling. Human endothelin-1 (Peptides International, Louisville, Kentucky) that had been shown to be chromatographically pure and nonpyrogenic was dissolved in Haemac/cel (Behring Werke, Marburg/Lahn, Marburg, FRG) and infused at a rate of 1.0, 2.5, and 5.0 ng/kg min (equivalent to 0.4, 1.0, and 2.0 pmol/ kg . min) for 15 minutes each. Arterial blood pressure was measured by the same person with a cuff sphygmomanometer every 5 minutes for 30 minutes before and until 60 minutes after the infusion of endothelin-1. Mean blood pressure was calculated as diastolic blood pressure plus one third of the pulse height. Basal blood pressure was defined as the mean of all blood pressure readings obtained in the 30-minute preinfusion period. Blood samples were drawn for the determination of potassium and sodium before and 60 minutes after the termination of the infusion of endothelin-1. Samples for the determination of the plasma concentrations of renin, aldosterone, and atrial natriuretic factor (ANF) were obtained at -15, 0, 15, 30, 45, 60, 75, 90, and 105 minutes. To define more closely the time course in plasma, endothelin-1 concentration samples for the determination of peptide's plasma concentrations were obtained at -15, -5, 0, 14, 15, 29, 30, 44, 45, 50, 55, 60, 75, 90, and 105 minutes. To determine the plasma concentrations of endothelin-1, 5 ml blood was collected into tubes

Endothelin-A Blockade Attenuates Systemic and Renal Hemodynamic Effects of L-NAME in Humans

“…Such changes in circulating ET-1 are much smaller than those that occur after anesthesia in rats, 29 and they are in any case still below the vasoconstrictor threshold both in vitro 30 and in vivo, as indicated for systemic and renal circulation in studies in humans undergoing ET-1 infusion. 18,31 We did not measure plasma ET-1 in this study, first because the above-reported evidence suggests that under our experimental conditions, significant variations in plasma ET-1 are very unlikely. In addition, plasma ET-1 may not reflect an increase in its tissue concentration due to an accentuated release of peptide on the basolateral side of endothelial cells.…”

Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor.

“…Although an effect on the kidney or atrial myocytes cannot be ruled out, an average endothelin concentration of 57 pmol/l during intravenous infusions did not influence plasma renin activity or plasma aldosterone and atrial natriuretic peptide concentrations in normal subjects. 17 Thus, it appears unlikely that reduced renal perfusion43 with an increase of renin or a release of atrial natriuretic peptide44 contributed to the vasoconstrictor and vasodilator responses to endothelin, respectively.…”

Working under pressure: the vascular endothelium in arterial hypertension

“…1,167 Endothelin acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyteadhesion to the vascular wall. 118 In addition to its arterial blood pressure rising effect in man, 168,169 ET-1 induces vascular and myocardial hypertrophy, [170][171][172] which are independent risk factors for cardiovascular morbidity and mortality. [173][174][175] Indeed, in patients with essential hypertension, carotid wall thickening and left ventricular mass correlate with reduced endothelium-dependent vasodilation.…”