Insulin-induced endothelin release and vasoreactivity in hypertriglyceridemic and hypertensive rats

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20-24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 microU/ml insulin resulted in increases in contractile responses: 41 +/- 5.9 and 57 +/- 6% for control and 65.5 +/- 6 and 95 +/- 9% for HTG aortas and femoral arteries, respectively. The endothelin ET(B)-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 +/- 8 and 53 +/- 5% in control and 48 +/- 13 and 79 +/- 3.5% in HTG aortas and femoral arteries, respectively. The ET(A)-receptor antagonist PD-151242 inhibited these responses by 12 +/- 10 and 1 +/- 9% in control and by 51.5 +/- 9 and 58.5 +/- 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.