EVIDENCE THAT PART OF THE NANC RELAXANT RESPONSE OF GUINEA-PIG TRACHEA TO ELECTRICAL-FIELD STIMULATION IS MEDIATED BY NITRIC-OXIDE

1 The nitric oxide (NO) synthesis inhibitors N(G)-monomethyl L-arginine (L-NMMA) and L-nitroarginine methyl ester (L-NAME) reduced relaxations of guinea-pig tracheal smooth muscle elicited by stimulation of intramural non-adrenergic, non-cholinergic (NANC) nerves, but D-NMMA had no effect. L-NAME was 10-30 times more potent than L-NMMA. Relaxations produced by sodium nitroprusside and vasoactive intestinal polypeptide (VIP) were not affected by L-NMMA or L-NAME. 2 The inhibitory effect of L-NMMA on NANC-mediated relaxations was partially reversed by L-arginine but was not affected by D-arginine. 3 VIP antibody and alpha-chymotrypsin abolished or greatly reduced the relaxant action of VIP and reduced relaxations elicited by stimulation of NANC nerves; the residual NANC relaxation was further reduced by L-NAME. 4 The results suggest that NO and VIP are mediators of NANC-induced relaxations of guinea-pig tracheal smooth muscle. We propose the term 'nitrergic' to describe transmission processes which are mediated by NO.