Exaggerated calcium signaling in preglomerular arteriolar smooth
muscle cells in genetic hypertension.
Iversen, Bjarne M., and William J. Arendshorst.
Department of Cell and Molecular Physiology University of North
Carolina at Chapel Hill Chapel Hill, NC 27599-7545
APStracts 5:0196F, 1998.
Experiments were conducted to gain insight into mechanisms responsible
for exaggerated renal vascular reactivity to angiotensin II (Ang II)
and vasopressin (AVP) in SHR during the development of hypertension.
Cytosolic calcium concentration ([Ca2+]i ) was measured by
ratiometric fura-2 fluorescence and a microscope-based photometer.
Vascular smooth muscle cells (SMC) from preglomerular arterioles were
isolated and disbursed using an iron oxide-sieving method combined
with collagenase treatment. Both Ang II and AVP produced rapid
increases in [Ca2+]i that remained elevated for the duration of
continued stimulation. Ang II elicited dose-dependent increases in
[Ca2+]i in groups of individual renal arteriolar SMC that were
similar for SHR and WKY. AVP, on the other hand, caused almost two
-fold larger responses in afferent arteriolar SMC from SHR. The
effects of Ang II were inhibited by the AT1 receptor antagonist
losartan. AVP action was blocked by the V1 receptor antagonist
(d(CH2)5,Tyr(NH2)9)-Arg-vasopressin. In SMC pretreated with
nifedipine, neither Ang II nor AVP elicited any [Ca2+]i response.
Addition of nifedipine after initiation of hormone action caused a
reversal of the elevated [Ca2+]i to basal levels. Short-term
reductions in external [Ca2+] by EGTA mimicked the effects of
nifedipine. Our study shows that Ang II and AVP activation of AT1 and
V1 receptors, respectively, stimulates [Ca2+]i by a common mechanism
characterized by preferential action on voltage-gated, L-type entry
channels sensitive to dihydropyridine agents in isolated
preglomerular arteriolar SMC. Calcium signaling in response to Ang II
activation of AT1 receptors does not differ between SHR and WKY,
suggesting that the exaggerated reactivity observed in vivo may be
secondary, perhaps dependent on interactions with other cell types,
e.g., endothelium. In contrast, AVP produced larger changes in
[Ca2+]i in preglomerular arteriolar SMC from SHR and such direct
effects can account for the observed enhanced renal blood flow
responses.
Received 11 February 1998; accepted in final form 22 October 1998
APS Manuscript Number F025-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998