NONADRENERGIC NONCHOLINERGIC NEUROTRANSMITTER OF FELINE TRACHEALIS - VIP OR NITRIC-OXIDE

We tested the hypothesis that vasoactive intestinal peptide (VIP) or nitric oxide (NO) is the nonadrenergic noncholinergic (ANC) neurotransmitter in feline trachealis. Isometric tension was measured in trachealis (open or closed tracheal rings) in vitro. Propranolol (10 muM) and atropine (1 muM) were present throughout the experiment, and smooth muscle tone was increased to 60-90% maximal with 5-hydroxytryptamine. We used three methodologies to reduce the relaxation function of VIP, which in turn should reduce NANC-mediated relaxation. 1) The putative VIP antagonist peptide T (10 muM) did not affect VIP concentration-response curves or electrical field stimulation- (EFS) induced NANC responses. 2) Incubation of tissue in specific VIP antiserum (16 h at 4-degrees-C) did not reduce EFS-induced NANC relaxations relative to tissue incubated in normal rabbit serum (P > 0.05). On the basis of our passive immunization techniques, it is not possible to absolutely reject VIP as the NANC transmitter. We speculate that nonspecific peptidases present in normal serum and VIP antiserum reduce EFS-induced responses similarly. 3) VIP desensitization, confirmed by a significant rightward shift (P < 0.01) in the VIP concentration-response curve, was achieved by exposing tissues (n = 11) to 1.0 muM VIP for 30 min. Desensitization did not reduce the EFS-induced NANC relaxatory response (P > 0.05) compared with control tissues, suggesting that VIP is not the NANC mediator. In contrast, the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10-30 muM) significantly (P < 0.01) attenuated EFS-induced relaxations to 4, 12.5, and 31.5% of the values obtained in time series control tissues at EFS of 5, 10, and 15 pulses/s respectively (P < 0.01). L-Arginine at a 10-fold higher concentration than N(G)-nitro-L-arginine methyl ester restored the EFS-induced relaxation to control values (P > 0.05). We suggest that VIP's involvement (if any) in NANC relaxation is minimal in feline airways and that NO is the primary mediator of feline NANC relaxation.