Prostacyclin contributes to inhibition of hypoxic pulmonary vasoconstriction by alkalosis.
The mechanism by which extracellular alkalosis inhibits hypoxic pulmonary vasoconstriction is unknown. We investigated whether the inhibition was due to intrapulmonary production of a vasodilator prostaglandin such as prostacyclin (PGI2). Hypoxic vasoconstriction in isolated salt-solution-perfused rat lungs was blunted by both hypocapnic and NaHCO3-induced alkalosis (perfusate pH increased from 7.3 to 7.7). The NaHCO3-induced alkalosis was accompanied by a significant increase in the perfusate level of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), an hydrolysis product of PGI2. Meclofenamate, an inhibitor of cyclooxygenase, counteracted both the blunting of hypoxic vasoconstriction and the increased level of 6-keto-PGF1 alpha. In intact anesthetized dogs, hypocapnic alkalosis (blood pH increased from 7.4 to 7.5) blunted hypoxic pulmonary vasoconstriction before but not after administration of meclofenamate. In separate cultures of bovine pulmonary artery endothelial and smooth muscle cells stimulated by bradykinin, the incubation medium levels of 6-keto-PGF1 alpha were increased by both hypocapnic and NaHCO3-induced alkalosis (medium pH increased from 7.4 to 7.7). These results suggest that inhibition of hypoxic pulmonary vasoconstriction by alkalosis is mediated at least partly by PGI2.
Yamaguchi
T
T
CVP Research Laboratory, Dept. of Medicine, University of Colorado Health Sciences Center, Denver 80262.
O'Brien
R F
RF
Hanson
W L
WL
Wagner
W W
WW
McMurtry
I F
IF
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000471:Alkalosis / Q000503:physiopathology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology; D011464:Epoprostenol / Q000096:biosynthesis*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D010100:Oxygen / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D017693:Sodium Bicarbonate; D014661:Vasoconstriction / Q000187:drug effects*
D001639:Bicarbonates; D002245:Carbon Dioxide; D015121:6-Ketoprostaglandin F1 alpha; D017693:Sodium Bicarbonate; D012964:Sodium; D011464:Epoprostenol; D010100:Oxygen; D001920:Bradykinin