Relative roles of calcium entry and mobilization signaling pathways
in angiotensin ii - induced constriction of renal resistance vessels
in vivo.
Ruan, Xiaoping, and William J. Arendshorst.
Department of Physiology, University of North Carolina at Chapel
Hill, Chapel Hill, NC 27599-75454
APStracts 2:0145F, 1995.
The purpose of this study was to determine the relative importance of
calcium signaling pathways in angiotensin?II (ANG?II) - induced renal
vasoconstriction in?vivo. Nifedipine was used to antagonize
dihydropyridine-sensitive, voltage-dependent calcium channels; BAY-K
8644 was employed to activate these calcium channels. Intracellular
calcium mobilization was evaluated using TMB-8 or heparin to inhibit
calcium release from sarcoplasmic reticulum. Renal blood flow was
measured by electromagnetic flowmetry in anesthetized, euvolemic
Wistar-Kyoto rats. The animals were pretreated with indomethacin to
avoid interactions with prostaglandins. ANG?II (2 hg) or BAY-K 8644
(1 [mu]g) was injected into the renal artery to produce a transient
30-50% decrease in renal blood flow without affecting arterial
pressure. Co-administration of nifedipine with BAY-K produced dose
-dependent inhibition of the maximum renal vasoconstriction elicited
by BAY-K 8644. The calcium-channel antagonist had similar effects on
ANG?II - induced renal vasoconstriction. Nifedipine exerted maximum
inhibition by blocking 50% of the peak ANG?II response. To evaluate
intracellular calcium mobilization, TMB-8 or heparin was co
-administered with ANG?II. Each agent produced dose-dependent
inhibition of up to 50% of the maximum renal vasoconstriction
produced by ANG?II. The inhibitory effects of nifedipine and TMB-8
were additive; neither agent had an effect when ANG?II AT1 receptors
were antagonized with losartan. These observations indicate that one
-half of the ANG?II - induced constriction of renal resistance vessels
is mediated by voltage-dependent, L-type calcium channels responsive
to the dihydropyridine nifedipine. The remaining 50% of the renal
vasoconstriction elicited by ANG?II is mediated by IP3-mediated
calcium mobilization from intracellular sources. The additive nature
of the inhibitory effects indicates distinct mechanisms involving
calcium mobilization and calcium entry signaling pathways which are
of equal importance in ANG?II activation of AT1 receptors to trigger
constriction of renal resistance vessels under basal conditions.
Received 5 June 1995; accepted in final form 16 August 1995.
APS Manuscript Number F178-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.