Role of arachidonic acid metabolites in hypoxic contractions of isolated porcine pulmonary artery and vein.
Recently it has been proposed that hypoxic pulmonary vasoconstriction (HPV) is mediated by local release of sulfidopeptide leukotriene products of the lipoxygenase pathway of arachidonic acid metabolism. In the present study the response to reduced oxygen supply of isolated porcine lobar pulmonary artery and pulmonary vein spiral strips has been studied. Contractions of the pulmonary artery (mean maximum tension 66.9 +/- 13.0 mg, n = 10) required an increase in baseline tone of the preparation followed by exposure to anoxia (mean bath PO2 O +/- 3 mm Hg), whereas contractions of the pulmonary vein (mean maximum tension 75.2 +/- 13.3 mg, n = 10) could be elicited in response to hypoxia alone (mean bath PO2 40 +/- 4 mm Hg). Indomethacin (5.6 microM), a cyclooxygenase inhibitor, attenuated the arterial contraction, but the mechanism may have been independent of the cyclooxygenase pathway since phenidone, an inhibitor of both cyclooxygenase and lipoxygenase pathways, had no effect. Inhibition by FPL 55712, a leukotriene end-organ antagonist, was achieved only at a high concentration (20 microM). In the case of the pulmonary vein, both indomethacin and phenidone inhibited the contractile response, whereas FPL 55712 had no effect. Contractile responses to reduced oxygen supply can be induced in isolated porcine pulmonary artery and vein strips, but probably are not mediated by leukotrienes.
Miller
D S
DS
Department of Medicine, University of Western Ontario, London, Canada.
Yaghi
A
A
Hamilton
J T
JT
Paterson
N A
NA
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011651:Pulmonary Artery / Q000503:physiopathology*; D011667:Pulmonary Veins / Q000503:physiopathology*; D011720:Pyrazoles / Q000494:pharmacology; D013552:Swine
D001095:Arachidonic Acids; D002867:Chromones; D011720:Pyrazoles; D006632:Histamine; C006312:FPL 55712; C015429:phenidone; D007213:Indomethacin