Effects of cyclic GMP elevation on isoprenaline-induced increase in cyclic AMP and relaxation in rat aortic smooth muscle: role of phosphodiesterase 3

摘要

1. In rat aortic rings precontracted with phenylephrine, the β-adrenoceptor agonist isoprenaline (10 nM to 30 μM) produces greater relaxant effects in preparations with endothelium than in endothelium-denuded preparations. The aim of this study was to determine the mechanisms involved in this effect and in particular investigate the possibility of a synergistic action between adenosine 3′: 5′-cyclic monophosphate (cyclic AMP) and guanosine 3′: 5′-cyclic monophosphate (cyclic GMP). 2. Isoprenaline-induced relaxation of rat aortic rings precontracted with phenylephrine was greatly reduced by the nitric oxide (NO) synthase inhibitor N~ω-nitro-L-arginine methyl ester (L-NAME, 300 μM) or the soluble guanylate cyclase inhibitors methylene blue (10 μM) or 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ, 10 μM) but unaffected by indomethacin (10 μM), a cyclo-oxygenase inhibitor. Similarly, in intact rings, the concentration-response curve of forskolin (10 nM to 1 μM) was shifted to the right upon endothelium removal or treatment with methylene blue.