ROLE OF NITRIC-OXIDE IN THE DILATOR ACTIONS OF CAPSAICIN-SENSITIVE NERVES IN THE RABBIT CORONARY CIRCULATION

Perivascular sensory nerves release calcitonin gene-related peptide (C ORP) and substance P, the dilator actions of which can be regulated by nitric oxide (NO). This study investigated the role of NO in the vaso dilation caused by sensory nerve stimulation, by capsaicin, or exogeno us CORP and substance P in the isolated perfused coronary circulation of the rabbit. Coronary perfusion pressure (CPP) was raised in order t o observe vasodilator responses, using the thromboxane mimetic, U46619 . Capsaicin (3 x 10(-6) moles), alpha CGRP (3 x 10(-11) moles) and sub stance P (3 x 10(-12) moles) caused comparable reductions in CCP. At t hese concentrations, responses to capsaicin and CORP were inhibited by the antagonist CGRP((8-37)) but unaffected by the neurokinin-l recept or antagonist, CP 96,345. The nitric oxide synthase inhibitor, N-G nit ro L-arginine methyl ester inhibited the effects of substance P and ca psaicin but not CGRP. These results suggest that CGRP release followin g capsaicin-induced sensory nerve activation is modulated by NO.