Hypoxic contraction of isolated rat pulmonary artery.
This study was undertaken to test if isolated rat pulmonary artery (PA) rings contract in response to hypoxia, if the response behaves similarly to previously described physiologic and pharmacologic features of hypoxic pulmonary vasoconstriction (HPV) in the isolated perfused rat lung and if the endothelium is necessary for the response. Rings (2-3 mm wide) cut from the main extrapulmonary PA branches were studied. Hypoxic contractions of up to 80 mg (mean +/- S.E. 34 +/- 5 mg, n = 20) were seen in resting rings. The contraction was more reproducible and was potentiated in rings prestimulated with either phenylephrine, norepinephrine, KCl, angiotensin II or the thromboxane mimetic U46619. The magnitude of the hypoxic contraction was proportional to the level of prestimulation and the severity of the hypoxia, with maximum hypoxic contraction seen during exposure to 0% oxygen. The hypoxic dose response showed a threshold bath pO2 of between 30 and 60 Torr, was potentiated by BAY K8644 (10(-7) M), was inhibited by both nifedipine (10(-7) M) and cooling to 29 degrees C and was not inhibited by meclofenamate (1.6 x 10(-6) M). All these characteristics are comparable to previously described features of HPV in the isolated perfused rat lung. Removal of the endothelium resulted in a 48-80% reduction in maximum PA hypoxic contraction. Similar hypoxic contraction was seen in precontracted aortic rings. We conclude that the hypoxic contraction of isolated rat PA may be a useful in vitro model of HPV, that both the endothelium and smooth muscle may be involved in the sensing of PO2 and that the direct hypoxic response is not unique to pulmonary arteries.
Rodman
D M
DM
Department of Medicine, University of Colorado Health Sciences Center, Denver.
Yamaguchi
T
T
O'Brien
R F
RF
McMurtry
I F
IF
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D003080:Cold Temperature; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010100:Oxygen; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D010656:Phenylephrine; D008469:Meclofenamic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D010100:Oxygen