BIG ET-1 INFUSION IN MAN CAUSES RENAL ET-1 RELEASE, RENAL AND SPLANCHNIC VASOCONSTRICTION, AND INCREASED MEAN ARTERIAL BLOOD-PRESSURE

Objective: The aim was to study the vascular effects of big endothelin -1 (big ET-1) infusion and its possible conversion to ET-1. Methods: S ix healthy subjects were given an intravenous infusion of big ET-1 in a dose of 8 pmol.kg(-1).min(-1) for 20 min. Blood samples were taken b efore, during, and up to 3 h after the infusion from arterial, hepatic , and renal vein catheters for the determination of splanchnic and ren al blood flows, as well as ET-1-like immunoreactivity (ET-1-LI) from t hese vascular beds. Results: Intravenous infusion of big ET-1 was foll owed by a doubling of arterial ET-1-LI from 4.17(SEM 0.39) to 8.42(0.4 9) pmol.litre(-1) (p < 0.001) and a significant increase in the renal release of ET-1-LI from 1.50(0.18) to 8.68(0.64) pmol.min(-1) (p < 0.0 01) but no splanchnic release. Big ET-1 infusion also caused a decreas e in heart rate from 57(4) to 45(3) beats.min(-1) (p < 0.001) and an i ncrease in mean arterial pressure from 86(1.3) to 106(3.2) mm Hg (p < 0.001), which lasted for at least 2 h. Renal blood flow fell from 1.38 (0.06) to 0.83(0.04) litre.min(-1) (p < 0.001) while splanchnic blood flow fell from 1.34(0.11) to 0.83(0.05) litre.min(-1) (p < 0.001). Con clusions: Big ET-1 infusion causes a drop in heart rate, an increase i n mean arterial pressure and decreases in splanchnic and renal blood f lows. Arterial plasma ET-1 levels doubled and big ET-1 infusion also i nduced a significantly increased renal, but not splanchnic, release of ET-1-LI, suggesting a unique renal handling of circulating big ET-1. When the results of the infusion of big ET-1 are compared with our pre vious experiments using ET-1 infusion, more marked haemodynamic change s (as reflected in the increase in mean arterial pressure, the drop in heart rate, and the duration of renal vasoconstriction) are seen desp ite lower arterial plasma ET-1-LI levels.