CIRCULATING LEVELS OF ENDOTHELIN-1 DURING ACUTE HYPERINSULINEMIA IN PATIENTS WITH ESSENTIAL-HYPERTENSION TREATED WITH TYPE-1 ANGIOTENSIN RECEPTOR ANTAGONIST OR PLACEBO

Insulin and angiotensin II (Ang II) are involved in the regulation of endothelin-1 (ET-1), This study investigates their possible influence on plasma levels of ET-1 in humans. Twenty patients with essential hyp ertension were included in a randomized, double-blind, placebo-control led crossover study of 4 weeks' treatment with losartan, a selective t ype 1 angiotensin (AT(1)) receptor antagonist. The effect was evaluate d in the fasting state and during acute hyperinsulinemia physiological ly induced by oral glucose ingestion (OGTT) and by euglycemic glucose clamp. Losartan lowered blood pressure significantly, but did not infl uence plasma levels of ET-1 in the fasting condition (5.2 +/- 0.2 fmol /ml on placebo and 5.6 +/- 0.3 fmol/ml after losartan treatment). Duri ng both models of acute hyperinsulinemia, there was a significant decr ease in plasma ET-1. In the OGTT the mean values after placebo treatme nt decreased from 5.2 +/- 0.2 fmol/ml at time 0 to 4.7 +/- 0.4 (P = .0 01) and 4.0 +/- 0.5 (P = .001) at 60 and 120 minutes, respectively. Du ring the clamp the mean ET-1 values decreased from 5.7 +/- 0.4 fmol/ml at time 0 to 4.6 +/- 0.2 (P < .001) and 4.3 +/- 0.3 (P = .006) at 60 and 120 minutes, respectively. No differences in these profiles occurr ed after losartan treatment, Significant inverse correlation between f asting levels of ET-1 and insulin sensitivity index was found, r = -.5 1, P = .003. In conclusion, losartan did not influence the circulating levels of ET-1 in basal condition or during acute hyperinsulinemia, w hereas a significant decrease in plasma ET-1 occurred during acute hyp erinsulinemia. A significant inverse correlation demonstrated between basal levels of plasma ET-1 and the insulin-stimulated glucose uptake could point to a possible regulatory influence of ET-1 production on g lucose metabolism or vice versa. Copyright (C) 1998 by W.B. Saunders C ompany.