Hypoxic contraction of pre-stretched human pulmonary artery.
To clarify the mechanism of hypoxic pulmonary vasoconstriction in man, human pulmonary artery segments (2 mm O.D.) were suspended and changes in isometric force were measured. The arteries were contracted by hypoxia (PO2 43 +/- 2 Torr) developing a tension of 127 +/- 36 mg over the course of 15 min. This contraction was completely blocked by 10(-6) M L-isoproterenol, 10(-6) M nitroglycerin, partially blocked by 10(-8)-10(-6) M verapamil, unchanged by 10(-6) M phentolamine, 10(-6) M L-propranolol, 10(-6) M diphenhydramine, 10(-6) M guanethidine, 10(-7) M FPL 55712 and enhanced by 10(-6) M BAY K 8644, 10(-3) M procaine, 3 x 10(-6) M quinacrine, 10(-6) M indomethacin or 10(-6) M methylene blue. Removal of the endothelium significantly enhanced the magnitude of hypoxia-induced contraction. These results suggest that the human pulmonary artery constricts in response to hypoxia, at least in part, through activation of the voltage-dependent Ca2+ channels and that neither alpha, beta, H1 receptors, the lipoxygenase pathway nor neural reflexes are involved. They also show that the endothelium is not required for hypoxic contraction and that its presence reduces sensitivity to hypoxia.
Ohe
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ogata
M
M
Katayose
D
D
Takishima
T
T
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000378:metabolism; D046508:Culture Techniques; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011651:Pulmonary Artery; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D001095:Arachidonic Acids; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011433:Propranolol; D014700:Verapamil; D008084:Lipoxygenase; D005996:Nitroglycerin; D010100:Oxygen