NONADRENERGIC NONCHOLINERGIC RELAXATION OF HUMAN PULMONARY-ARTERIES IS PARTIALLY MEDIATED BY NITRIC-OXIDE

Nonadrenergic noncholinergic (NANC) vasodilator mechanisms may contrib ute to the maintenance of low vascular resistance characteristic of th e pulmonary circulation. Previous studies have demonstrated that nitri c oxide (NO) is the principal NANC neurotransmitter in guinea pig pulm onary arteries. We examined whether NANC relaxation could be demonstra ted in human pulmonary arteries, and the role of NO in this phenomenon . Fresh human pulmonary artery rings, with and without an intact endot helium, were mounted in organ baths containing Krebs' solution and pre contracted with U44069 (0.3 mu M). Adrenergic and cholinergic neurostr ansmitter pathways were blocked with guanethidine and atropine, respec tively (10 mu M each). In both endothelium-intact and -denuded vessels , electrical field stimulation (EFS, 1 to 10 Hz, 100 V) resulted in a frequency-dependent relaxation (maximal relaxation of 25 +/- 4% and 15 +/- 2% in endothelium-intact and -denuded vessels, respectively). Tet rodotoxin (0.3 mu M) abolished the EFS-induced relaxation. L-N-G-nitro -arginine methyl ester (L-NAME, 10 mu M), was used to block enzymatic synthesis of NO. In both endothelium-intact and -denuded vessels, L-NA ME reduced NANC relaxation to approximately 50% of control values. Thi s reduction was reversible with the application of L-arginine (100 mu M). We conclude that NANC relaxation exists in human pulmonary arterie s and that it is partly mediated through NO.