COX and the control of the pulmonary circulation.
The lung possesses a low resistance circulation that must, at all times, accommodate the entire cardiac output. Moreover, to ensure proper oxygenation of hemoglobin, blood flow must be directed to well-ventilated lung units, i.e., ventilation and perfusion must be matched. Cyclooxygenase (COX)-mediated arachidonic acid (AA) metabolites can influence both pulmonary vascular resistance and ventilation-perfusion matching. In isolated dog and rabbit lungs, ventilation of the right lung with oxygen (O2) and the left lung with nitrogen (N2) resulted in normal perfusion pressures and blood gas tensions. In both species, administration of COX inhibitors resulted in redistribution of blood flow from hypoxic alveoli (N2-ventilated lung) to the well-oxygenated alveoli (O2-ventilated lung) and an increase in arterial oxygen tension, i.e., a COX-mediated AA metabolite or metabolites opposed hypoxic pulmonary vasoconstriction (HPV), but, by virtue of this activity, prevented optimal matching of ventilation with perfusion. The effects of COX inhibition were reversed by prostacyclin (PGI2). These findings are consistent with the hypothesis that COX-derived products of AA metabolism can influence ventilation-perfusion matching in the lung. Moreover, the results of studies in dogs suggest that one such metabolite of AA is PGI2.
Sprague
Randy S
RS
Department of Pharmacological and Physiological Science, School of Medicine, Saint Louis University, 1402 South Grand Boulevard, St. Louis, MO 63119, USA. spraguer@slu.edu
Stephenson
Alan H
AH
Olearczyk
Jeffery J
JJ
Lonigro
Andrew J
AJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D010100:Oxygen