Endothelium-dependent modulation of endothelin-induced vasoconstriction and membrane depolarization in cat cerebral...

Effects of endothelin, the newly discovered, endothelium-derived vasoactive peptide, were examined on isolated, pressurized cat arteries. Responses to increasing concentrations of porcine endothelin (10(-12) to 10(-8) M) were compared in endothelium intact and denuded vessel segments utilizing diameter and membrane potential measurements. Endothelin produced a concentration-dependent contraction in arteries with intact endothelium with a maximal response of 26 +/- 2.8% of the initial diameter in physiological saline solution at 100 mm Hg of intraluminal pressure. Removal of the endothelium sensitized the smooth muscle to endothelin and increased the maximal response to 48 +/- 2.3% of the initial diameter. After incubation of the intact vessels with 10(-5) M indomethacin, the endothelin response was potentiated to the maximal value of 66 +/- 1.26% of the initial diameter of the intact vessels, and to 61 +/- 2.6% of the denuded arteries. The arterial smooth muscle cells were depolarized by 6 +/- 0.45 mV after administration of endothelin to the vessels, and by 10 +/- 0.8 mV in the denuded vessels. This depolarization was not altered by indomethacin. Our data suggest that endothelin has a direct effect on the smooth muscle of cat cerebral vascular tissue, and the sensitivity of these vessels to endothelin may be modulated by the release of dilatory cyclooxygenase products derived from the intact endothelium.