Vascular effects of platelet-activating factor in lambs: role of cyclo- and lipoxygenase.
In adult sheep, platelet-activating factor (PAF) effects include systemic hypotension and pulmonary hypertension. To identify developmental differences in vascular responses to PAF, we studied the effects of C18- and C16-PAF in 49 +/- 2- (SE) day-old lambs. Responses of upstream (arteries and microvessels) and venous segments of the lung to C18-PAF were determined both in vivo and in isolated lungs. In isolated lungs, the role of eicosanoids in PAF effects was also determined. In vivo, both C18- and C16-PAF caused a significant increase in systemic and pulmonary vascular resistance. The magnitude of vascular responses to C16-PAF was greater than that to C18-PAF. C18-PAF constricted both upstream and venous segments of the pulmonary circulation. Cyclooxygenase inhibition in isolated lungs attenuated arterial constriction to C18-PAF, whereas simultaneous cyclooxygenase and lipoxygenase inhibition completely blocked the effects of C18-PAF. In summary, in contrast to PAF effects in adult sheep, PAF constricts both systemic and pulmonary vessels in lambs, with significant pulmonary venous constriction. Eicosanoids, especially lipoxygenase products, play a major role in mediating PAF effects in the lung.
Toga
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Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, Torrance 90509.
Hibler
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Ibe
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Raj
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D000758:Anesthesia; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013329:Structure-Activity Relationship; D014655:Vascular Resistance / Q000187:drug effects
D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases