Prostaglandin synthetase inhibitors do not decrease hypoxic pulmonary vasoconstriction.
Prostaglandins are naturally occurring substances with powerful vasoactive effects that are released from tissues during hypoxia or ischemia. Several workers have suggested that a prostaglandin may help to mediate the pulmonary vascular pressor response to alveolar hypoxia. To investigate this possibility, we have measured the pressor responses to hypoxia before and after prostaglandin synthesis antagonism with meclofenamate in eight anesthetized dogs, two groups of awake calves (n=10 and =5), and nine isolated, perfused rat lungs. In addition, synthesis was inhibited by the use of indomethacin in nine additional dogs. The stability of the pulmonary vascular response to repeated hypoxic challenges was demonstrated in nine other dogs. In each species and with both prostaglandin antagonists, the pulmonary pressor responses to hypoxia were significantly increased rather than reduced. We conclude that prostaglandins do not mediate the pulmonary vasoconstriction caused by hypoxia. The consistent increase observed suggests that hypoxic vasoconstriction stimulates prostaglandin synthesis, the net effect of which is pulmonary vasodilatation which opposes the constriction.
D000818:Animals; D002417:Cattle; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000188:drug therapy*; D007213:Indomethacin / Q000627:therapeutic use*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D008297:Male; D008469:Meclofenamic Acid / Q000627:therapeutic use*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011453:Prostaglandins / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects; D051381:Rats; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D006899:Mixed Function Oxygenases; D007213:Indomethacin