A POSSIBLE ROLE OF NITRIC-OXIDE FORMATION IN THE VASODILATATION OF RABBIT EAR ARTERY INDUCED BY A TOPICALLY APPLIED CAPSAICIN ANALOG

Effects of topical application of a capsaicin analogue, nonylic acid v anillylamide (NVA, 0.032-10.0 mM) on the arterial diameter in the ear skin were examined in conscious rabbits using a precise dial caliper. In addition, the possibility of nitric oxide (NO) participating in a v asodilatation induced by low concentrations of NVA was tested by an NO synthase inhibitor. At the lowest concentration of NVA (0.032 mM), no significant change in the diameter was observed after external applic ation of the NVA ointment. At concentrations of 0.32 mM or more, NVA p roduced a significant vasodilator response. However, at higher concent rations of 3.2 and 10.0 mM, -NVA induced substantial shrinkage in the arterial diameter and oedema formation, which was not affected by L-NA ME (N-G-nitro-L-arginine methyl ester, 3 mg/kg, i.v.), suggesting flui d leakage induced by oedema from the vessels might suppress the vasodi latation. Thus, the concentration-response curve for NVA was bell-shap ed. NVA (0.32 mM)-induced vasodilatation was not significantly affecte d by atropine (1 mg/kg, i.v.) or propranolol (80 mu g/kg, i.v.). Howev er,the NVA-induced vasodilatation was completely suppressed by an NO s ynthase inhibitor, L-NAME (3 mg/kg, i.v.) which had no influence on th e resting diameter, but not by an inactive stereoisomer, D-NAME (3 mg/ kg, i.v.). These findings suggest that vanilloid receptor activation r esults in the release of sensory neuropeptides, which in turn stimulat e the synthesis of endothelial NO which is responsible for the vasodil atation.