The effects of
ONO 3708, a new
thromboxane A2 receptor antagonist, on cardiovascular and airway responses, at an early phase during
endotoxin shock were investigated in anesthetized dogs. The i.v. infusion (1mg.kg-1) of E.coli
endotoxin caused an increase in mean pulmonary artery pressure (MPAP) from 9.9 +/- 1.0 to 19.1 +/- 2.3 mmHg at 5 min, and at 15 min after infusion, elevated MPAP returned toward the control level. Pretreatment with
ONO 3708 abolished these effects of
endotoxin on pulmonary artery pressure at an early phase. The change in airway pressure reached a maximum of 14.4 +/- 1.7 cmH2O from 10.0 +/- 1.9 at 5 min, followed by a gradual decline toward a baseline value at 30 min in the control group.
ONO 3708 significantly attenuated increase in airway pressure induced by E. coli
endotoxin. But pretreatment with
ONO 3708 could not prevent decrease in systemic arterial pressure and cardiac output induced by
endotoxin. These results suggest that role of
thromboxane A2 on the cardiovascular response during
endotoxin shock is played only on pulmonary vascular changes, and
ONO 3708 has a beneficial effect at least during the early phase of
endotoxin shock.