Renal microvascular actions of calcitonin gene-related peptide.
Reslerova, Martina, and Rodger Loutzenhiser.
Smooth Muscle Research Group, Department of Pharmacology and
Therapeutics, The University of Calgary. Department of Medicine,
Indiana University, School of Medicine, Indianapolis, Indiana
APStracts 5:0049F, 1998.
Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is
suggested to act via ATP-sensitive K channels (KATP). In the present
study, we examined the actions of CGRP on pressure- and angiotensin
II-induced vasoconstriction using the in vitro perfused
hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mm Hg)
and 0.1 nM angiotensin II elicited similar decreases in afferent
diameter in this model. CGRP inhibited myogenic reactivity in a
concentration-dependent manner, completely preventing pressure
-induced constriction at 10 nM (95+/-10% inhibition). These effects
were partially attenuated by 10 [mu]M glibenclamide (62+/-16%
inhibition, p=0.025), indicating both KATP-dependent and KATP
-independent actions_ of CGRP. In contrast, 10 nM CGRP inhibited
angiotensin II-induced vasoconstriction by only 54+/-11% and this
action was not affected by glibenclamide (41+/-11%, p=0.31). CGRP
also inhibited the efferent arteriolar response to angiotensin II in
the absence and presence of glibenclamide. Pinacidil (1.0 [mu]M), a
KATP opener also preferentially inhibited pressure- versus
angiotensin II-induced vasoconstriction (97+/-5% and 59+/-13%
inhibition, respectively, p=0.034). We conclude that the renal
vasodilatory mechanisms of CGRP are pleiotropic and involve both
KATP-dependent and -independent pathways. The effectiveness of CGRP
in opposing renal vasoconstriction and the role of KATP in this
action appear to depend on the nature the underlying
vasoconstriction. We suggest that this phenomenon reflects an
inhibition of KATP activation by angiotensin II.
Received 19 November 1997; accepted in final form 18 February
1998.
APS Manuscript Number F360-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 9 March 1998