Inhibitory effect of endothelin on renin release in vitro.

We previously reported that endothelin inhibits renin release in a dynamic superfusion system of collagenase-dispersed rat renal cortical cells. In the present report we investigated cellular mechanisms by which endothelin inhibits renin release from juxtaglomerular (JG) cells. In a superfusion system of dispersed rat renal cortical cells, 10(-10) M endothelin inhibited renin release stimulated by 5 x 10(-8) M isoproterenol or 5 x 10(-5) M 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8, a putative intracellular Ca antagonist). Endothelin showed a slight but significant inhibitory effect on renin release stimulated by isoproterenol or TMB-8 even in the absence of extracellular Ca. Endothelin also inhibited renin release in the presence of 10(-4) M nicardipine. In a superfusion system of renal cortical slices, both 10(-8) M endothelin and a high concentration (60 mM) of K inhibited renin release, and 10(-6) M nicardipine attenuated the inhibition of renin release by high K but did not affect the inhibition by endothelin. These results suggest that endothelin inhibits renin release from JG cells not only by the promotion of Ca influx into the cells through dihydropyridine-insensitive Ca channels but also by other mechanism(s) independent of extracellular Ca.