TY - JOUR
T1 - Superoxide anion mediates the endothelium-dependent contractions to serotonin by regenerated endothelium
AU - Lin, P. J.
AU - Pearson, P. J.
AU - Cartier, R.
AU - Schaff, H. V.
PY - 1991
Y1 - 1991
N2 - The endothelium modulates vascular tone by releasing a variety of vasoactive compounds that relax or contract the underlying vascular smooth muscle. We have previously demonstrated that regenerated endothelium exhibits endothelium-dependent hypercontraction to the platelet-derived compound serotonin (or 5-HT). To determine if this hypercontraction is mediated by superoxide anion produced by the endothelium, we performed balloon catheter denudation on the thoracic and abdominal aorta of male Lewis rats. Eight weeks after arterial injury, endothelium-dependent responses to serotonin were examined in tissue bath experiments. Vascular rings (5 mm in length), with and without endothelium, were contracted with norepinephrine and then exposed to serotonin (10-9 to 3 x 10-5 mol/L). Vascular rings with regenerated endothelium exhibited hypercontraction to serotonin (251% ± 25% of initial norepinephrine contraction; p < 0.05 compared with control rings, 175% ± 13%). Removal of the endothelium (133% ± 6%) or treatment with superoxide dismutase (184% ± 7%), with or without catalase, prevented the endothelium-dependent constrictor effect of the serotonin. Ketanserin suppressed the vasoconstrictor effect of serotonin on control (93% ± 15%) and regenerated (105% ± 9%) rings with endothelium, indicating that the serotonin effect is mediated through the 5-HT2-serotonergic receptor. Deferoxamine or heat-inactivated superoxide dismutase did not modify the response. These observations support the hypothesis that superoxide anion is an endothelium-derived contracting factor produced by regenerated endothelium after intimal injury.
AB - The endothelium modulates vascular tone by releasing a variety of vasoactive compounds that relax or contract the underlying vascular smooth muscle. We have previously demonstrated that regenerated endothelium exhibits endothelium-dependent hypercontraction to the platelet-derived compound serotonin (or 5-HT). To determine if this hypercontraction is mediated by superoxide anion produced by the endothelium, we performed balloon catheter denudation on the thoracic and abdominal aorta of male Lewis rats. Eight weeks after arterial injury, endothelium-dependent responses to serotonin were examined in tissue bath experiments. Vascular rings (5 mm in length), with and without endothelium, were contracted with norepinephrine and then exposed to serotonin (10-9 to 3 x 10-5 mol/L). Vascular rings with regenerated endothelium exhibited hypercontraction to serotonin (251% ± 25% of initial norepinephrine contraction; p < 0.05 compared with control rings, 175% ± 13%). Removal of the endothelium (133% ± 6%) or treatment with superoxide dismutase (184% ± 7%), with or without catalase, prevented the endothelium-dependent constrictor effect of the serotonin. Ketanserin suppressed the vasoconstrictor effect of serotonin on control (93% ± 15%) and regenerated (105% ± 9%) rings with endothelium, indicating that the serotonin effect is mediated through the 5-HT2-serotonergic receptor. Deferoxamine or heat-inactivated superoxide dismutase did not modify the response. These observations support the hypothesis that superoxide anion is an endothelium-derived contracting factor produced by regenerated endothelium after intimal injury.
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U2 - 10.1016/s0022-5223(19)36520-1
DO - 10.1016/s0022-5223(19)36520-1
M3 - Article
C2 - 1652668
AN - SCOPUS:0025954710
SN - 0022-5223
VL - 102
SP - 378
EP - 385
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 3
ER -