title: Endothelium-dependent response of human internal mammary artery to hypoxia.
abstract: To study the effect of hypoxia on vascular tone in human internal mammary artery (IMA), segments of IMA were suspended in organ chambers and contracted with norepinephrine (at a dose producing 30% of maximal contraction). Exposure of IMA segments with endothelium to hypoxia (partial pressure of oxygen, 38 +/- 4 mmHg) resulted in a transient relaxation (47 +/- 6%) followed by constriction (177 +/- 8%) (n = 14). IMA segments without endothelium exhibited a gradual decrease in tension that almost completely counteracted vasoconstriction. The initial transient endothelium-dependent relaxation could be blocked by indomethacin (10(-6)M) and was associated with a 51% increase in 6-ketoprostaglandin F1 alpha production (n = 22, P < 0.05). The endothelium-dependent contraction to hypoxia could be attenuated by indomethacin (n = 6, P < 0.05) or NG-monomethyl-L-arginine (10(-5)M; n = 9, P < 0.05) and was completely blocked by combination of these agonists (n = 6, P < 0.05). These experiments indicate that on exposure to hypoxia, the human IMA exhibits an initial prostacyclin-mediated relaxation followed by contraction due to the production of a constrictor prostanoid in addition to the inhibition of basal production of endothelium-derived relaxing factor.
authors.affiliation: Section of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: P J
authors.initials: PJ
authors.lastname: Pearson
authors.forename: P J
authors.initials: PJ
authors.lastname: Lin
authors.forename: P R
authors.initials: PR
authors.lastname: Evora
authors.forename: H V
authors.initials: HV
authors.lastname: Schaff
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008323:Mammary Arteries / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D015121:6-Ketoprostaglandin F1 alpha; D001120:Arginine; D009638:Norepinephrine; D007213:Indomethacin