INVOLVEMENT OF NITRIC-OXIDE AND PEPTIDES IN THE INHIBITORY NONADRENERGIC, NONCHOLINERGIC (NANC) RESPONSE IN BOVINE MESENTERIC-ARTERY

The cyclic GMP mediated non-adrenergic non-cholinergic (NANC) relaxation in field stimulated bovine mesenteric artery and its modulation by various factors was studied. Electrical field stimulation of precontracted (Phe 2.5 muM or histamine 5 muM) bovine mesenteric arteries resulted in relaxations varying between 10-70% in different preparations. Tetrodotoxin (3 muM) completely blocked the inhibitory NANC response. Preincubation with high concentrations (100 muM - 1 mM) of N(G)-nitro-L-arginine for 15 min. significantly reduced the relaxation induced by electrical field stimulation. Blockade of cyclooxygenases and prostaglandin synthesis by indomethacin had no effect on the relaxatory response to electrical field stimulation. Neither the alpha2-adrenoceptor selective antagonist yohimbine (1 muM) nor the alpha2-adrenoceptor selective agonist UK 14,304 (1 muM) had any significant effect on the electrical field stimulation-induced relaxation. Pertussis toxin (100 ng/ml) was without effect on relaxations elicited by electrical field stimulation. GTP in the concentration range 10 muM - 1 mM slightly potentiated the relaxant response. N-carboxymethyl-Phe-Leu (an inhibitor of enkephalinase) or aprotinin (an inhibitor of several proteases) had no significant effect on the electrical field stimulation response. Addition of trypsin (100 U/ml) in combination with chymotrypsin (20 U/ml) significantly reduced the electrical field stimulation-induced relaxation. In the present study we have found indications for the involvement of nitric oxide and possibly also peptides in mediating the inhibitory NANC response (relaxation) in bovine mesenteric arteries.