The Possible Involvement of Nitric Oxide/Endothelium Derived Relaxing Factor in Atropine-Induced Vasorelaxation

Atropine has been used to block cholinergic neurotransmission in basic research. Large doses of atropine cause vasodilation of the blood vessels in the skin. This effect is apparently unconnected with the antimuscarinic activity of atropine and seems to be due to a direct action on the blood vessels. It has been suggested that atropine blocks muscarinic receptors at low doses and it induces the release of endothelium derived relaxing factor (EDRF) at large doses. This study examined the effects of atropine on isolated rat pulmonary artery rings with or without endothelium intact in the absence and presence of nitric oxide synthase inhibitors, N-omega nitro-L-arginine methyl ester (L-NAME) or N-omega nitro-L-arginine (L-NOARG) that precontracted with phenylephrine (PHE), 5-hydroxy-tryptamine (5-HT) or KCl. Atropine (1 nM) blocked the vasorelaxant effect of acethylcholine (1 µM) in pulmonary artery rings precontracted with PHE (100 nM). Atropine (10 nM-5 μM) also produced concentration dependent relaxation in these rings precontracted with PHE or 5-HT, but did not relax rings precontracted with KCl. The vasorelaxant effects of atropine were partially inhibited by the mechanical remove of endothelium or pretreatment the rings with L-NAME or L-NOARG, although they were not statistically significant. These results suggest that the ability of atropine to relax pulmonary artery rings may be dependent upon the mechanism of action of the precontracting agonist and also, the vasorelaxant effect of atropine is not wholly mediated by the release of NO (nitric oxide)/EDRF.