Although endothelin (ET) is a potent vasoconstrictor that is produced in the vascular endpthelium, the role of its local release in modulating vascular smooth muscle tone is unknown. To assess this, porcine coronary resistance vessels were dissected and studied in vitro. Upon warming, the resistance artencs developed spontaneous tone and constricted from 185 ±15 um (SEM) to 132 ±11 urn (p<01,D=7). After selective ETA receptor blockade with the nonpeptide antagonist PD156707 (107M), diameter increased submaximally to 162 ±17 urn (jX.05 vs tone). Subsequent addition of LNAME (lO-4M) to inhibit nitric oxide synthase reduced diameter to 149 ±18 |jm (pK.05 vs PD156707). The effects of ETA receptor blockade to exogenous ET are summarized below: % Maximal Constriction at 10-7 M ET 10-18M 10-9M 10-6M Control <n=8) 45±9 79 ±11 100 ±5 PD156707 (n=7) -7 ±8-5 ±826 ±18PD±LNAME(n=8) 9±712±951±11 values mean ±SEM p<0.01 vs control Iliese data indicate that ET released from endothelial cells afffytit vascular smooth muscle tone. The submaximal vasodilation following ETA receptor blockade is due to both a reduction in ETA-mediated constriction and an unopposed ETB mediated release of nitric oxide. This' "Suggests that locally released ET may compete with nitric oxide and modulate tone in the coronary resistance vasculatu re.
|Original language||English (US)|
|State||Published - Dec 1 1996|