Original Article

Effects of ONO-1078, a leukotriene antagonist, on cardiovascular responses induced by vagal stimulation, capsaicin, and substance P in guinea pigs

Authors: Er-qing WEI, Xiao-hua XIN, Yao-chen WANG, Li-ping CHEN, Li-fen ZHANG, Ru-lian BIAN

Abstract

AIM:
To determine the role of ONO-1078, 4-oxo-8 -[p-(4-phenylbutyloxy) benzoylamino]- 2-(tetrazol-5-yl) -4H-1-benzopyran hemihydrate, in cardiovascular responses induced by vagal stimulation, capsaicin, and substance P.
METHODS:
Evans blue extravasation in the atrium and ventricle, and mean arterial pressure (MAP) were observed.
RESULTS:
Electric stimulation of vagus (ESV, 10 Hz, 5 ms, 2 or 10 V, for 90 s) increased Evans blue extravasation in the hearts of atropine (1 mg.kg-1, i.v.)-pretreated guinea pigs. Capsaicin (0.05 mg.kg-1, i.v.) and substance P (1 microgram.kg-1, i.v.) enhanced the dye extravasation and elicited a drop in MAP. ONO-1078 (0.03 and 0.1 mg.kg-1, i.v.) inhibited ESV-induced response, especially at stimulation of 2 V. ONO-1078 (0.03 mg.kg-1) attenuated capsaicin-induced cardiac microvascular leakage and hypotensive response, but failed to inhibit substance P-induced responses.
CONCLUSION:
ONO-1078 can modulate the cardiovascular responses in neurogenic inflammation, possibly mediated by inhibiting sensory neuropeptide release.
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