4.6 Article

Aerobic exercise training reduces ET-1-mediated vasoconstriction and improves endothelium-dependent vasodilation in postmenopausal women

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AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00674.2022

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ETA receptors; menopause; vascular function

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Aerobic exercise training reduces ET-1-mediated vasoconstriction and improves endothelium-dependent vasodilation in postmenopausal women.
Endothelin-1 (ET-1) contributes to vascular dysfunction in postmenopausal women (PMW). Although aerobic exercise is beneficial in reducing ET-1-mediated vasoconstrictor tone in men, it is unknown whether this favorable vascular effect occurs in women. We tested the hypothesis that aerobic exercise training reduces ET-1-mediated vasoconstriction in PMW. We further hypothesized that reductions in ET-1 vasoconstrictor tone underly exercise-induced improvements in endothelium-dependent vasodilatation in PMW. Forearm blood flow (FBF) responses to intra-arterial infusion of selective ETA receptor blockade (BQ-123, 100 nmol/ min for 60 min) and acetylcholine (4.0, 8.0, and 16.0 mu g/100 mL tissue/min) in the absence and presence of ETA receptor blockade were determined before and after a 12-wk aerobic exercise training intervention in 18 healthy, sedentary PMW (58 +/- 4 yr). Women exercised an average of 4.9 +/- 0.7 day/wk for 51 +/- 7 min/day at 71 +/- 3% of maximal heart rate. Before exercise, BQ-123 significantly increased FBF (-25%) in sedentary PMW; however, this effect was abolished following the exercise intervention. FBF responses to acetylcholine were also significantly higher after exercise training (from 4.2 +/- 1.2 to 14.0 +/- 3.8 mL/100 mL tissue/min) versus before (from 4.1 +/- 1.0 to 11.4 +/- 3.3 mL/100 mL tissue/min; -25% increase; P < 0.05). Before exercise training, coinfusion of BQ-123 with acetylcholine enhanced (-25%; P < 0.05) the vasodilator response (from 4.4 +/- 1.1 to 13.9 +/- 4.2 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. 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.NEW & NOTEWORTHY Endothelin-1 (ET-1) contributes to declines in endothelial function in postmenopausal women. To our knowledge, we show for the first time that aerobic exercise reduces ET-1-mediated vasoconstriction in previously sedentary postmenopausal women. Moreover, aerobic exercise improved endothelial-dependent dilation due in part to the reductions in ET-1mediated vasoconstriction.

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