Thromboxane and prostacyclin release after endotoxin infusion in the rat

Abstract

To determine in the rat whether pulmonary artery hypertension accompanies thromboxane release, we sequentially monitored pulmonary and systemic artery pressures and cardiac output. We measured pulmonary and aortic plasma levels of TxB₂ as well as 6-keto-prostaglandin F₁α (6-keto-PGF₁α) in awake unrestrained adult male Sprague-Dawley rats given a single infusion of endotoxin at the relatively high dose commonly administered to this endotoxin-resistant species. At 40 min after endotoxin infusion, both pulmonary and aortic TxB₂ and 6-keto-PGF₁α levels increased nine-fold and seven-fold above baseline, respectively. In the pulmonary artery, 40 min after infusion, both mediator levels differed significantly from baseline (p<0.05), whereas in the aorta, because of marked variance in the response of different animals, only the 6-keto-PGF₁α levels achieved significance (p<0.05). These changes were associated with a fall in systemic blood pressure and cardiac output, but no demonstrable rise in pulmonary artery pressure (PAP). Despite ultrastructural evidence of vascular injury, these data indicate that in the rat thromboxane and prostacyclin release following a single infusion of endotoxin is not associated with pulmonary hypertension and that increased prostacyclin production may contribute to systemic hypotension.