Effects of 8-epi-prostaglandin F2 alpha and U46,619 on pulmonary hemodynamics in piglets.
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-PGF2 alpha, for its biological properties on the pulmonary vasculature in young piglets. We first compared 8-epi-PGF2 alpha 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-PGF2 alpha 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-PGF2 alpha 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-PGF2 alpha, 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-PGF2 alpha. We conclude that 8-epi-PGF2 alpha can contribute to pulmonary vasoconstriction in young piglets in a dose-dependent reversible manner and that it acts primarily via pulmonary vascular Tx receptors.
Truog
W E
WE
Section of Neonatal Medicine, Children's Mercy Hospital, Kansas City, Mo 64108-9898, USA. wtruog@cmh.edu
Norberg
M
M
Thibeault
D W
DW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C054215:SQ 30741; C075750:8-epi-prostaglandin F2alpha; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost