Cultured dog aortic endothelial cells release vasodilatory products in response to acetylcholine and adenosine.

We tested the hypothesis that products released from contracting skeletal muscle could induce the release of vasodilatory products from vascular endothelium. Superfused endothelium-denuded rabbit aortic and dog femoral artery rings contracted with 1 microM phenylephrine delivered at 1-2 mL/min were subjected to 3-mL bolus challenges that had been briefly exposed to either a culture dish devoid of endothelial cells (control) or a dish containing dog aortic endothelial cells (experimental) immediately prior to their application. Challenges were alternated and included Krebs-Henseleit bicarbonate buffer (Krebs) pH 7.4 (vehicle); 1 microM acetylcholine; and the muscle metabolites 6 mM potassium chloride, 1 mM sodium phosphate monobasic, 10 microM adenosine, acidic Krebs pH 6.8, and 100 microM ammonium chloride. Only the products released from cultured endothelial cells after the addition of acetylcholine and adenosine resulted in a significant relaxation of vascular rings compared with control. Prior incubation of the cultured endothelial cells with 10 microM 8-phenyltheophylline eliminated the relaxation induced by adenosine, and all relaxations were eliminated by prior incubation of the cells with either 10 microM N omega-nitro-L-arginine or a combination of 10 microM indomethacin and 10 microM nordihydroguaiaretic acid. This indicates that at least one metabolite released from contracting skeletal muscle could induce the release of vasodilatory products from the endothelium, which would act as a local amplifier of functional hyperemia.