BLOCKADE OF CHLORIDE CHANNELS BY DIDS STIMULATES RENIN RELEASE AND INHIBITS CONTRACTION OF AFFERENT ARTERIOLES

Calcium-activated chloride channels have been proposed to control reni n release from juxtaglomerular cells and to be involved in the excitat ion-contraction coupling of the renal afferent arteriole. The hypothes is was tested on renin release from rat glomeruli and in microperfused rabbit afferent arterioles with the chloride channel blocker 4,4'-dii sothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was e qually enhanced by omission of extracellular calcium and by addition o f 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. T he stimulatory effects of low calcium [with or without ethylene glycol -bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was supp ressed and the stimulatory effect of DIDS was abolished. The DIDS-indu ced enhancement of renin release was not dependent on bicarbonate. Nor epinephrine (5 X 10(-7)-1 X 10(-6) M) and angiotensin II (1 X 10(-8)-1 0(-6) M) evoked reversible and dose-dependent contractions of microper fused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the bas al diameter of the arterioles but strongly inhibited the response to a ngiotensin II and attenuated the duration of the contractile response to norepinephrine. The results support the hypothesis that DIDS-sensit ive calcium-activated chloride channels are involved in regulation of renin release and in the afferent arteriolar contraction after angiote nsin II but do not play a pivotal role in the response to norepinephri ne.