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 (CGRP) and substance P, the dilator actions of which can be regulated by nitric oxide (NO). This study investigated the role of NO in the vasodilation caused by sensory nerve stimulation, by capsaicin, or exogenous CGRP and substance P in the isolated perfused coronary circulation of the rabbit. Coronary perfusion pressure (CPP) was raised in order to observe vasodilator responses, using the thromboxane mimetic, U46619. Capsaicin (3 x 10(-6) moles), alpha CGRP (3 x 10(-11) moles) and substance P (3 x 10(-12) moles) caused comparable reductions in CCP. At these concentrations, responses to capsaicin and CGRP were inhibited by the antagonist CGRP(8-37) but unaffected by the neurokinin-1 receptor antagonist, CP 96,345. The nitric oxide synthase inhibitor, NG nitro L-arginine methyl ester inhibited the effects of substance P and capsaicin but not CGRP. These results suggest that CGRP release following capsaicin-induced sensory nerve activation is modulated by NO.
Mitchell
J A
JA
Department of Applied Pharmacology, National Heart and Lung Institute, London, UK.
Williams
F M
FM
Williams
T J
TJ
Larkin
S W
SW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000294:innervation*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester