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Hypertension. 2007;50:403-409
Published online before print June 18, 2007, doi: 10.1161/HYPERTENSIONAHA.107.088294
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(Hypertension. 2007;50:403.)
© 2007 American Heart Association, Inc.


Original Articles

Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Gary P. Van Guilder; Christian M. Westby; Jared J. Greiner; Brian L. Stauffer; Christopher A. DeSouza

From the Integrative Vascular Biology Laboratory (G.P.V.D., C.M.W., J.J.G., B.L.S., C.A.D.), Department of Integrative Physiology, University of Colorado, Boulder; Department of Medicine (B.L.S., C.A.D.), University of Colorado at Denver Health Sciences Center, Denver; and Denver Health Medical Center (B.L.S.), Colo.

Correspondence to Christopher DeSouza, Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, 354 UCB, Boulder, CO 80309. E-mail desouzac{at}colorado.edu

Increased endothelin-1–mediated vasoconstrictor tone has been linked to the etiology of a number of pathologies associated with human aging, including hypertension, congestive heart failure, and coronary artery disease. However, it is currently unclear whether aging, per se, is associated with enhanced endothelin-1 system activity. We hypothesized that endothelin-1 vasoconstrictor activity is greater in healthy older compared with young men and that regular aerobic exercise is an effective intervention for reducing endothelin-1 vasoconstrictor tone in older previously sedentary men. Forearm blood flow (plethysmography) responses to intra-arterial infusion of endothelin-1 (5 pmol/min; for 20 minutes) and selective (BQ-123; 100 nmol/min; for 60 minutes) and nonselective (BQ-123+BQ-788; 100 nmol/min; for 60 minutes) endothelin-1 receptor blockade were determined in 28 healthy, sedentary men: 13 younger (age: 27±1 years) and 15 older (age: 62±2 years). The vasoconstrictor response to endothelin-1 was significantly blunted ({approx}65%) in the older versus younger men. In response to BQ-123, resting forearm blood flow increased ({approx}20%; P<0.05) in the older but not in the younger men. The addition of BQ-788 to BQ-123 did not significantly affect the blood flow responses to BQ-123 in either group. Eight of the 15 older sedentary men completed a 3-month aerobic exercise intervention. After the intervention, the vasoconstrictor response to endothelin-1 was markedly increased (225%; P<0.05), whereas BQ-123 resulted in modest vasoconstriction in the previously sedentary older men. These results demonstrate that endothelin-1–mediated vasoconstrictor tone increases with age in healthy men but can be alleviated with regular aerobic exercise.


Key Words: elderly • exercise • endothelin • blood flow regulation


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