Role of nitric oxide and guanosine 35-cyclic monophosphate in mediating nonadrenergic noncholinergic relaxation in guinea-pig pulmonary arteries.

摘要

1. Nonadrenergic, noncholinergic (NANC) nerves mediate vasodilatation in guinea-pig pulmonary artery (PA) by both endothelium-dependent and endothelium-independent mechanisms. The transmitter(s) involved in the endothelium-independent pathway have not yet been identified. We have therefore investigated the possibility that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) may mediate this neural vasodilator response in guinea-pig branch PA rings denuded of endothelium. 2. Electric field stimulation (EFS, 50 V, 0.2 ms) induced a frequency-dependent (1-24 Hz), tetrodotoxin-sensitive relaxation of the U44069-precontracted PA rings in the presence of adrenergic and cholinergic blockade. 3. The NO synthase inhibitors NG-monomethyl L-arginine (L-NMMA, 100 microM) and NG-nitro L-arginine methyl ester (L-NAME, 30 microM), and the guanylyl cyclase inhibitor methylene blue (5 microM) inhibited the EFS (16 Hz)-induced relaxation by 53 +/- 5, 74 +/- 9 and 82 +/- 9% respectively (n = 5-7, P < 0.01, compared with control rings). 4. Excess concentrations of L-, but not D-arginine (300 microM) completely reversed the inhibitory effect of L-NMMA. 5. The EFS-elicited relaxation (4 Hz) was potentiated by 1 microM zaprinast, a type V phosphodiesterase inhibitor which inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) degradation, but was unaffected by 0.1 microM zardaverine, a type III/IV phosphodiesterase inhibitor which inhibits cyclic AMP degradation. 6. EFS (50 V, 0.2 ms, 16 Hz) induced a 3 fold increase in tissue cyclic GMP content, an action which was inhibited by L-NMMA (100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)