Nonadrenergic noncholinergic vasodilation of guinea pig pulmonary arteriesis mediated by nitric oxide

Nonadrenergic noncholinergic (NANC) mediated vasodilation may contribute to the maintenance of low pulmonary vascular tone. The NANC neurotransmitters , nitric oxide (NO) and the sensory neuropeptides, substance P and calciton in gene related peptide (CGRP), were investigated as possible mediators of NANC vasodilation in guinea pig pulmonary arteries. Fresh guinea pig pulmon ary artery rings, with and without an intact endothelium, were mounted in o rgan baths containing Krebs solution and precontracted with the prostagland in F-2 alpha analogue U44069. In both endothelium-intact and denuded vessel s, electrical field stimulation (1-12 Hz) in the presence of guanethidine a nd atropine resulted in a frequency-dependent vasodilation. The peptide fra gment hCGRP(8-37), a competitive antagonist of the CGRP receptors, the pept ide fragment NK1 antagonist SP4-11, and the nonpeptide NK1 antagonist RP675 80 had no effect on NANC vasodilation, In both endothelium-intact and denud ed vessels, N-G-nitro-L-arginine methyl eater (L-NAME), an inhibitor of NO synthesis, inhibited NANC vasodilation, an effect that was reversible with L-arginine. We conclude that NANC vasodilation in guinea pig pulmonary arte ries is mediated predominantly through NO activity.