THE INDUCTION OF NITRIC OXIDE-MEDIATED RELAXATION OF HUMAN ISOLATED PULMONARY-ARTERIES BY PACAP

1 The effects of pituitary adenylate cyclase-activating peptide (PACAP ) and vasoactive intestinal peptide (VIP) were analysed in human isola ted circular segments of pulmonary arteries. Guinea-pig pulmonary arte ries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) syntha se inhibitor N-G-monomethyl L-arginine (L-NMMA). 2 PACAP and VIP induc ed concentration-dependent relaxations of precontracted pulmonary arte ries. The maximal dilator response (I-max, %) and the potency (EC(50) value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea-pig segments. PACAP and VI P were both more potent that acetylcholine (ACh). 3 Removal of the vas cular endothelium abolished the PACAP induced dilator response in pulm onary arteries from both species. The VIP induced dilatation was unaff ected, whereas the response to ACh was abolished. L-NMMA given before PACAP inhibited the dilatation. Furthermore, L-NMMA also reversed the dilatation already induced by PACAP and excess concentrations of L-arg inine restored the dilator response of the L-NMMA treated arteries. 4 PACAP is a potent dilator of human pulmonary arteries. Although the di later effect seems to be similar in amplitude to the one induced by VI P, the present results suggest differences in the underlying mechanism s of action (endothelium-dependency) between the two peptides.