A possible role of nitric oxide formation in the vasodilatation of rabbit ear artery induced by a topically applied Capsaicin analogue.
Effects of topical application of a capsaicin analogue, nonylic acid vanillylamide (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 vasodilatation 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 application of the NVA ointment. At concentrations of 0.32 mM or more, NVA produced a significant vasodilator response. However, at higher concentrations of 3.2 and 10.0 mM, -NVA induced substantial shrinkage in the arterial diameter and oedema formation, which was not affected by L-NAME (NG-nitro-L-arginine methyl ester, 3 mg/kg, i.v.), suggesting fluid leakage induced by oedema from the vessels might suppress the vasodilatation. Thus, the concentration-response curve for NVA was bell-shaped. NVA (0.32 mM)-induced vasodilatation was not significantly affected by atropine (1 mg/kg, i.v.) or propranolol (80 micrograms/kg, i.v.). However, the NVA-induced vasodilatation was completely suppressed by an NO synthase inhibitor, L-NAME (3 mg/kg, i.v.) which had no influence on the resting diameter, but not by an inactive stereoisomer, D-NAME (3 mg/kg, i.v.). These findings suggest that vanilloid receptor activation results in the release of sensory neuropeptides, which in turn stimulate the synthesis of endothelial NO which is responsible for the vasodilatation.
Department of Veterinary Pharmacology, Faculty of Agriculture, Iwate University, Japan.
T
T
Suzuki
S
S
Wada
N
N
Tomizawa
R
R
Kamata
S
S
Saito
I
I
Sato
E
E
Sugawara
E
E
Tachikawa
H
H
Kobayashi
D000287:Administration, Topical; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000098:blood supply; D004487:Edema; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002211:Capsaicin; C040937:nonivamide; D019331:NG-Nitroarginine Methyl Ester