Sandner, Peter and Kornfeld, Mark and Ruan, Xiaoping and Arendshorst, William J. and Kurtz, Armin (1999) Nitric oxide cAMP interactions in the control of rat renal vascular resistance. CIRCULATION RESEARCH, 84 (2). pp. 186-192. ISSN 0009-7330,
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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-omega-nitro-L-arginine methyl ester (L-NAME; 1 mmol/L) and of NO administration by sodium nitroprusside (SNP, 10 mu mol/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-1-methyl-3-(2-methylpropyl)-xanthine; 8-MMIBMX, 20 mu moyL] and PDE-4 (rolipram, 20 mu mol/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 mu mol/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 mu mol/L), our findings an 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; CGMP-INHIBITED PHOSPHODIESTERASE; ARTERIAL SMOOTH-MUSCLE; MOLECULAR-CLONING; SELECTIVE-INHIBITION; GUANYLYL CYCLASE; GENE-EXPRESSION; GMP; RELAXATION; RECEPTOR; cGMP; phosphodiesterase; renal blood flow |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Nov 2022 07:18 |
| Last Modified: | 22 Nov 2022 07:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48529 |
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