Different modes of sensory neuropeptides and nitric oxide involvement in 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 stimulation (TNS)-induced non-adrenergic, non-cholinergic (NANC) relaxation in isolated guinea pig anterior mesenteric artery (AMA) and posterior 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-46619, TNS induced relaxation, which was almost completely abolished by capsaicin pretreatment (10(-6) M, 15 minutes). In AMA, a CGRP1 receptor antagonist (human CGRP8-37, 10(-5) M) significantly attenuated the relaxation, while did both human CGRP8-37 (10(-5) M) and neurokinin-1 receptor antagonists (spantide, 2 x 10(-5) M and FK888, 3 x 10(-6) M) in PCV. NG-nitro-L-arginine methyl ester (10(-4) M) did not significantly attenuate either the NANC-or CGRP-induced relaxation in AMA. However, it significantly did attenuate both the NANC-and SP-induced relaxation, and it also considerably attenuated CGRP-induced relaxation although insignificantly, in PCV. Thus, CGRP could be significantly responsible for the NO-independent NANC relaxation in AMA, whereas both CGRP and SP could additionally relax PCV in a NO-dependent manner.