Vasoconstriction to hypoxia of the human internal mammary artery.

Experiments were designed to determine the role of the endothelium in response to hypoxia in the human internal mammary artery (IMA). Segments of IMA were harvested during coronary artery bypass surgery. Rings (4 mm in length) of IMA, with and without endothelium, were suspended to force transducers in organ baths containing a physiologic salt solution (37 degrees C, 95% O2/5% CO2, and pH = 7.4). The rings were contracted with norepinephrine (NE, 1 x 10(-7) M, initial tension), and then exposed to hypoxia (95% N2/5% CO2, PO2 = 35 +/- 5 mmHg). In IMA segments with endothelium, hypoxia caused an initial, transient relaxation (hypoxic inhibition) to 52 +/- 9% of the initial tension, followed by contraction of the blood vessel (hypoxic potentiation; 178 +/- 10% of initial tension). In vessels without endothelium, hypoxia only induced relaxation (to 10 +/- 2% of initial tension). In vessels with endothelium, reoxygenation induced transient rapid relaxation (to 31 +/- 12%; post-hypoxic inhibition) which then stabilized to 50 +/- 14% of the initial tension. However, segments without endothelium returned to their initial tension. Indomethacin (1 x 10(-5) M) reduced the endothelium-dependent hypoxic contraction and abolished the hypoxic and post-hypoxic inhibition. Free radical scavengers (superoxide dismutase plus catalase and deferoxamine) did not modify the responses to hypoxia and reoxygenation. These experiments indicate that hypoxia induces the release of an endothelium-derived constricting cyclooxygenase product from the human IMA endothelium, and that reoxygenation causes release of a cyclooxygenase-dependent endothelium-derived relaxing factor. The release of endothelium-derived constricting factor(s) could induce vasospasm and cause cardiovascular collapse if IMA grafts are exposed to hypoxia perioperatively.