Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb.
Eight near-term fetal lambs were studied acutely in utero to determine role of platelet-activating factor (PAF) in the regulation of vasomotor tone in systemic and pulmonary circulations in the immediate perinatal period. Four fetal lambs were studied predelivery and 2 h postdelivery to determine circulating PAF levels. Aortic and pulmonary arterial pressures and cardiac output were measured continuously, and systemic and pulmonary vascular resistances were calculated. Left pulmonary arterial blood flow was also measured in four fetal lambs. After delivery and oxygenation, circulating PAF levels fell significantly. When WEB-2170, a specific PAF-receptor antagonist, was infused to block effect of endogenous PAF in the eight near-term fetal lambs, systemic vascular resistance fell 30% but pulmonary vascular resistance fell dramatically by 68%. Specificity of WEB-2170 was tested in juvenile lambs and was found to be very specific in lowering vasomotor tone only when tone was elevated by action of PAF. Our data show that endogenous PAF levels in the fetus contribute to maintain a high basal systemic and pulmonary vasomotor tone and that a normal fall in circulating PAF levels after birth and oxygenation may facilitate fall in pulmonary vascular resistance at birth.
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Department of Pediatrics, University of California, Los Angeles, School of Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
Hibler
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Raj
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012756:Sheep; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; D014662:Vasoconstrictor Agents; C039351:platelet activating factor receptor; D000804:Angiotensin II; C063964:bepafant