Abstract P095: Aerobic Exercise Training Reduces Endothelin-1-mediated Vasoconstriction In Postmenopausal Women

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Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in postmenopausal women (PMW), contributing to their increased cardiovascular risk. Although aerobic exercise is beneficial in reducing ET-1 system activity in men, it is unknown whether this favorable vascular effect is conferred in women. In fact, contrary to men, it is uncertain whether aerobic exercise training improves endothelial dysfunction in PMW. We tested the hypothesis that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. We further hypothesized reductions in ET-1 vasoconstrictor tone underly exercise-induced improvements in endothelium-dependent vasodilatation in PMW. Methods: Forearm blood flow (FBF) responses to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol/min for 60 min), acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) in the absence and presence of ET A receptor blockade and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) were determined before and after a 12-week aerobic exercise training intervention in 20 healthy, sedentary PMW (56 + 1 yr). Results: All 20 PMW completed the exercise intervention, walking an average of 4.9 + 0.1 d/wk for 50 + 2 min/d at 71 + 1% of maximal heart rate. After the exercise intervention, BQ-123 elicited no significant change in resting FBF in the previously sedentary PMW compared with significant vasodilation (~25%) before exercise. FBF responses to acetylcholine were markedly higher (~25%; P<0.05) after (from 4.3 + 0.3 to 13.8 + 0.8 mL/100 ml tissue/min) vs before (from 4.1 + 0.2 to 11.3 + 0.8 mL/100 ml tissue/min) exercise training. Moreover, before exercise training the co-infusion of BQ-123 with acetylcholine enhanced (~25%; P<0.05) the vasodilator response (from 4.3 + 0.3 to 13.7 + 0.7 mL/100 mL tissue/min) compared with acetylcholine alone; after exercise training, the presence of BQ-123 did not significantly affect the vasodilator response to acetylcholine. Conclusions: These data demonstrate that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. Furthermore, decreased ET-1-mediated vasoconstriction is an important mechanism underlying aerobic exercise-induced improvement in endothelium-dependent vasodilation in PMW.