© 1999 American Heart Association, Inc.
Original Contribution |
Nitric Oxide/cAMP Interactions in the Control of Rat Renal Vascular Resistance
From Institut für Physiologie der Universität Regensburg (P.S., M.K., A.K.), Regensburg, Germany; and Department of Cell and Molecular Physiology (X.R., W.J.A.), University of North Carolina at Chapel Hill, NC.
Correspondence to Peter Sandner, PhD, Institut für Physiologie I, Universität Regensburg, D-93040 Regensburg, Germany. E-mail peter.sandner{at}vkl.uni-regensburg.de
Abstract—This study aimed to
characterize the interaction between nitric oxide (NO)- and
cAMP-related pathways in the control of renal blood flow. Using the
isolated perfused rat kidney model, we determined the effects of
inhibition of NO formation by
N
-nitro-L-arginine methyl
ester (L-NAME; 1 mmol/L) and of NO administration by sodium
nitroprusside (SNP, 10 µmol/L) on renal vascular resistance
under conditions of elevated vascular cAMP levels. cAMP levels were
increased either by adenylate cyclase activation via
isoproterenol or by inhibition of cAMP phosphodiesterases (PDEs) 1, 3,
and 4. We found that L-NAME markedly increased vascular resistance and
that this effect was completely reversed by SNP. Both isoproterenol and
inhibitors of the cAMP PDEs lowered basal vascular
resistance. In the presence of isoproterenol (3 nmol/L) and
inhibitors of PDE-1
[8-methoxymethyl-l-methyl-3-(2-methylpropyl)-xanthine;
8-MM-IBMX, 20 µmol/L] and PDE-4 (rolipram, 20
µmol/L), L-NAME again substantially increased vascular resistance,
and this effect of L-NAME was completely reversed by SNP. In the
presence of the PDE-3 inhibitors milrinone (20
µmol/L) and trequinsin (200 nmol/L), however, both L-NAME and SNP
failed to exert any additional effects. Because PDE-3 is a
cGMP-inhibited cAMP PDE and because the vasodilatory effect of SNP was
abrogated by the guanylate cyclase inhibitor
1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (20
µmol/L), our findings are compatible with the idea that an action of
NO on PDE-3 could account for the vasodilatory properties of NO on the
renal vasculature. Moreover, our findings suggest that PDE-3 activity
is an important determinant of renal vascular resistance.
Key Words: cGMP • phosphodiesterase • renal blood flow
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