[Effects of thromboxane A2 on chronic hypoxic pulmonary hypertension in the rat].

Chronic hypoxia (10% O2 for 2-3 weeks) causes pulmonary hypertension and vascular remodeling in the rat. To study the role of thromboxase A2 in chronic hypoxic pulmonary hypertension, the hemodynamic effects of intravenous administration of a thromboxane analogue (STA2) were measured in chronic hypoxic (H) and normoxic (N) Sprague-Dawley rats. During anesthesia baseline pulmonary arterial pressure (PAP) was higher in H rats (34.6 +/- 1.0 mmHg) than in N rats (18.4 +/- 1.2 mmHg). Intravenous STA2 (0.3 microgram) acutely increased pulmonary artery pressure by 74% +/- 11% (25 +/- 4 mmHg) in H rats and by 47% +/- 2% (9 +/- 1 mmHg) in N rats, which indicates that both the absolute and relative acute pulmonary vasoconstriction caused by STA2 were greater in H rats. The changes in systemic arterial pressure caused by STA2 were smaller than the changes in pulmonary arterial pressure both in H rats (11% +/- 3%) and in N rats (17% +/- 3%). Lungs were isolated and perfused with saline, and the vasoconstrictive response to 0.05 microgram of STA2 in lungs (14.5 +/- 2.4 mmHg) from H rats was greater than the response to 0.1 microgram of STA2 (5.6 +/- 1.3 mmHg) in lungs from N rats. To examine whether blockade of calcium channels could suppress the vasoconstrictor response to STA2, the effects of the calcium channel blocker nicardipine hydrochloride on vasoconstriction caused by STA2 were measured in H and N rats. In vivo, the blockade of calcium channels suppressed the increase in pulmonary artery pressure caused by STA2. This suppression was greater in H rats (56% +/- 11%) than in N rats (25% +/- 4%). Similar results were obtained with isolated perfused lungs. Blockade of calcium channels suppressed the vasoconstriction caused by STA2 and this suppression was greater in H rats than in N rats. The finding that thromboxane A2 induced greater vasoconstriction in H rats than in N rats indicates that thromboxane A2 may play an important role in pulmonary hypertension, and suggests that blockade thromboxane A2 may benefit some patients with primary and secondary pulmonary hypertension. Furthermore, the finding that suppression of thromboxane-induced vasoconstriction by blockade of calcium channels was greater in H rats than in N rats indicates that such treatment may also benefit some patients.