Blockade of chloride channels by dids stimulates renin release and
inhibits contraction of afferent arterioles.
Jensen, Boye L., & Ole Skott.
Department of Medical Physiology, University of Copenhagen,
Denmark
APStracts 2:0192F, 1995.
Calcium-activated chloride channels have been proposed to control
renin release from juxtaglomerular cells and to be involved in the
excitation-contraction coupling of the renal afferent arteriole. The
hypothesis was tested on renin release from rat glomeruli and in
micro perfused rabbit afferent arterioles with the chloride channel
blocker 4,4'-diisothiocyanato stilbene-2,2'-disulfonic acid (DIDS).
Renin secretion was equally enhanced by omission of extracellular
calcium and by addition of 0.5 mM DIDS. The inhibitory effect of
calcium was blocked by DIDS. The stimulatory effects of low calcium
(with or without EGTA) and DIDS were not additive. In the absence of
chloride, basal renin release was suppressed and the stimulatory
effect of DIDS was abolished. The DIDS-induced enhancement of renin
release was not dependent on bicarbonate. Norepinephrine (5*10-7
-1*10-6 M) and angiotensin II (1*10-8-10-6 M) evoked reversible and
dose-dependent contractions of microperfused, rabbit afferent
arterioles. DIDS (0.5 mM) did not affect the basal diameter of the
arterioles but strongly inhibited the response to ang II, and
attenuated the duration of the contractile response to
norepinephrine. The results support the hypothesis that DIDS
-sensitive calcium-activated chloride channels are involved in
regulation of renin release and in the afferent arteriolar
contraction after angiotensin II while they do not play a pivotal
role in the response to norepinephrine.
Received 18 October 1994; accepted in final form 23 October 1995.
APS Manuscript Number F375-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95