Effects of 8-Epi-Prostaglandin F2α and U46,619 on Pulmonary Hemodynamics in Piglets

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Abstract
Non-cyclooxygenase-derived prostaglandin F2- (PGF2)-like compounds can be formed by membrane lipid peroxidation. We sought to characterize one member of this class of compounds, 8-epi-PGF2α, for its biological properties on the pulmonary vasculature in young piglets. We first compared 8-epi-PGF2α to a thromboxane (Tx) mimetic, U46,619, to determine relative pulmonary vasoconstrictive effects. We next determined if the vasoconstriction induced by both agonists would be reversed by 50 ppm of inhaled nitric oxide (NO). We also determined the degree of inhibition of U46,619 and of 8-epi-PGF2α by a Tx receptor antagonist, SQ 30,741. Anesthetized, ventilated piglets (18 ± 2 days, 3.7 ± 0.5 kg) were infused with randomly selected doses of U46,619 and of 8-epi-PGF2α to describe dose-response curves plotting pulmonary vascular resistance (PVRi) against dose. When a maximal dose was achieved, inhaled NO (50 ppm) was administered. Results for the calculated PVRi (mm Hg/l/min/kg) are as follows (mean ± SD): for U46,619, baseline value: 43 ± 10, peak dose: 165 ± 46, and peak dose with NO: 73 ± 33; for 8-epi-PGF2α, baseline value: 38 ± 9, peak dose: 138 ± 30, and peak dose with NO: 72 ± 25, and for both drugs, PVRi at peak dose was greater than at baseline (p < 0.001). PVRi at peak dose plus NO also remained elevated above baseline (p < 0.05; repeated measures ANOVA). The Tx receptor antagonist SQ 30,741 (1–10 mg/kg) inhibited U46,619-induced pulmonary vasoconstriction completely; however, the 1 mg/kg dose provided only 90% inhibition against 8-epi-PGF2α. We conclude that 8-epi-PGF2α can contribute to pulmonary vasoconstriction in young piglets in a dose-dependent reversible manner and that it acts primarily via pulmonary vascular Tx receptors.

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