Possible involvement of thromboxane in bronchoconstrictive and hypertensive effects of LTC4 and LTD4 in guinea pigs

Abstract

The actions of leukotriene (LT) C4 and D4 on the systemic arterial pressure and the insufflation pressure in guinea pigs and rabbits were examined. In guinea pigs, 0.3 - 3 nmole/kg of LTC4 and 0.1 - 1.0 nmole/kg of LTD4 administrated from left jugular vein caused dose-dependent increase of the airway resistance measured by the Konzett-Rössler method and a triphasic blood pressure response; an initial hypotension, a secondary hypertension and a third long-lasting hypotension. All of the hypertensive phase and 100 - 150% of the increase of the airway resistance by LTC4 and LTD4 were inhibited by a selective thromboxane synthetase inhibitor, OKY-1581 (10 mg/kg, i.v.) and only the hypotension was observed. Indomethacin (10 mg/kg, i.p.) also inhibited not only the airway resistance increase, but also the prolonged hypotension by LTC4 and shortened the duration of the hypotension by LTD4. It is suggested that thromboxane might be involved in bronchoconstriction and hypertensive effects by LTC4 and LTD4 and that hypotensive prostaglandin might be involved in the hypotensive phase after LTC4 and LTD4. In rabbits, the increase of the airway resistance by LTC4 and LTD4 (upto 100 nmole/kg, i.v.) was negligible and only the hypotension was observed.