DIFFERENT MODES OF SENSORY NEUROPEPTIDES AND NITRIC-OXIDE INVOLVEMENTIN RELAXATION OF GUINEA-PIG VESSELS

This study investigated involvement of calcitonin-gene-related peptide (CGRP), substance P (SP) and nitric oxide (NO) in transmural nerve st imulation (TNS)-induced non-adrenergic, non-cholinergic (NANC) relaxat ion in isolated guinea pig anterior mesenteric artery (AMA) and poster ior caval vein (PCV). Effects of cyclo-oxygenase-generated eicosanoids were blocked with indomethacin (10(-5) M) and so were adrenergic and cholinergic responses with phentolamine (3 X 10(-6) M), propranolol(10 (-6) M) and atropine (10(-6) M). In both vessels precontracted by U-46 619, TNS induced relaxation, which was almost completely abolished by capsaicin pretreatment(10(-6) M, 15 minutes). In AMA, a CGRP(1) recept or antagonist (human CGRP(8-37), 10(-5) M) significantly attenuated th e relaxation, while did both human CGRP (8-37) (10(-5) M) and neurokin in-1 receptor antagonists (spantide, 2X10(-5) M and FK888, 3X10(-6) M) in PCV. N-G-nitro-L-arginine methyl ester (10(-4) M) did not signific antly attenuate either the NANC-or CORP-induced relaxation in AMA. How ever, it significantly did attenuate both the NANC-and SP-induced rela xation, and it also considerably attenuated CORP-induced relaxation al though insignificantly, in PCV. Thus, CORP could be significantly resp onsible for the NO-independent NANC relaxation in AMA, whereas both CG RP and SP could additionally relax PCV in a NO-dependent manner.