Effects of prostaglandin H2 on perinatal pulmonary circulation.
A pivotal intermediate in prostaglandin (PG) biosynthesis is the endoperoxide PGH2. This endoperoxide is capable of eliciting direct responses in biological systems without undergoing conversion to other PGs. Effects of PGH2 include stimulation of platelet aggregation and vascular smooth muscle contraction in vitro; injections of PGH2 in vivo cause increases in pulmonary arterial pressure. The response of the pulmonary vasculature of perinatal lambs to PGH2 was measured using an in situ pump-perfused left lower lung preparation. Intrapulmonary injections of PGH2 (0.24-0.61 microgram/kg) into six unventilated fetal lambs (0.93-0.97 gestation) produced decreases in pulmonary vascular resistance (PVR) of 10-21%. The fall in PVR was rapid in onset, reached a peak at 10 s after injection, and returned to baseline within 35 s. Following ventilation (FIO2 = 0.21) of fetal lambs, injections of PGH2 (0.24-0.61 microgram/kg) caused increases in PVR (ave increase = 50% over control PVR). The pulmonary pressor response to PGH2 in ventilated fetal lambs was depressed almost 50% by inhibition of thromboxane synthetase. Injections of a "heat-inactivated" PGH2 did not affect PVR in ventilated fetuses. We did not observe any effects on systemic blood pressure or heart rate of intrapulmonary arterial injections of PGH2. These findings suggest a metabolism of PGH2 to dilator PGs before ventilation and constrictor PGs and thromboxanes after ventilation, and/or direct effects of PGH2 on vascular smooth muscle that are dependent on existing vascular tone.
D000818:Animals; D005260:Female; D008168:Lung / Q000196:embryology*; D011247:Pregnancy; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D044262:Prostaglandin H2; D013930:Thromboxane-A Synthase