Investigation of the interaction between nitric oxide and vasoactive intestinal polypeptide in the guinea-pig gastric fundus.

The interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) was investigated in isolated circular smooth muscle cells and strips of the guinea-pig gastric fundus. VIP induced a concentration-dependent inhibition of carbachol-induced contraction in smooth muscle cells with a maximum at 10−6 M. The relaxation by 10−6 M VIP was inhibited for 79.1±5.8% (mean±s.e.mean) by the NO-synthase (NOS) inhibitor L-NG-nitroarginine (L-NOARG; 10−4 M) in a L-arginine reversible way. Also the inducible NOS (iNOS) selective inhibitor N-(3-(acetaminomethyl)-benzyl)acetamide (1400 W; 10−6 M) inhibited the VIP-induced relaxation, but its inhibitory effect was not reversed by L-arginine. When cells were incubated with the guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ, 10−6 M), the protein kinase A-inhibitor (R)-p-cyclic adenosine-3′,5′-monophosphothioate ((R)-p-cAMPS, 10−6 M) and the glucocorticoid dexamethasone (10−5 M), the relaxant effect of VIP was decreased by respectively 80.9±7.6, 77.0±11.6 and 87.1±4.5%. In circular smooth muscle strips of the guinea-pig gastric fundus, the VIP (10−9–10−7 M)-induced relaxations were not significantly influenced by 10−4 ML-NOARG, 10−6 M 1400 W, 10−6 M ODQ and 10−5 M dexamethasone. These results suggest that iNOS, possibly induced by the procedure to prepare the smooth muscle cells, is involved in the relaxant effect of VIP in isolated smooth muscle cells but not in smooth muscle strips of the guinea-pig gastric fundus. This study illustrates the importance of the experimental method when studying the influence of NOS inhibitors on the relaxation induced by VIP in gastrointestinal smooth muscle preparations. British Journal of Pharmacology (2000) 129, 751–763; doi:10.1038/sj.bjp.0703089