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


CONCLUSIONS
ONO-1078 can modulate the cardiovascular responses in neurogenic inflammation, possibly mediated by inhibiting sensory neuropeptide release.
Wei
E Q
EQ
Department of Pharmacology, Zhejiang Medical University, Hangzhou, China.
Xin
X H
XH
Wang
Y C
YC
Chen
L P
LP
Zhang
L F
LF
Bian
R L
RL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002199:Capillary Permeability; D002211:Capsaicin / Q000037:antagonists & inhibitors; D002317:Cardiovascular Agents / Q000037:antagonists & inhibitors; D002867:Chromones / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000037:antagonists & inhibitors; D014630:Vagus Nerve / Q000502:physiology
D002317:Cardiovascular Agents; D002867:Chromones; D013189:SRS-A; D013373:Substance P; D002211:Capsaicin; C047681:pranlukast