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Exercise restores -adrenergic vasorelaxation in aged rat carotid arteries

¹Chair of Geriatrics and ²Chair of Internal Medicine, Department of Clinic Medicine, Cardiovascular, and Immunological Sciences, University of Naples "Federico II," 80131 Naples; and ³Department of Gerontology, Geriatrics, and Metabolic Diseases, II University of Naples, 80131 Naples, Italy

Submitted 14 January 2003 ; accepted in final form 6 March 2003

Aging is associated with alterations in -adrenergic receptor (-AR) signaling and reduction in cardiovascular responses to -AR stimulation. Because exercise can attenuate age-related impairment in myocardial -AR signaling and function, we tested whether training could also exert favorable effects on vascular -AR responses. We evaluated common carotid artery responsiveness in isolated vessel ring preparations from 8 aged male Wistar-Kyoto (WKY) rats trained for 6 wk in a 5 days/wk swimming protocol, 10 untrained age-matched rats, and 10 young WKY rats. Vessels were preconstricted with phenylephrine (10^-6 M), and vasodilation was assessed in response to the -AR agonist isoproterenol (10^-10-3 x 10^-8 M), the ₂-AR agonist UK-14304 (10^-9-10^-6 M), the muscarinic receptor agonist ACh (10^-9-10^-6 M), and nitroprusside (10^-8-10^-5 M). -AR density and cytoplasmic -AR kinase (-ARK) activity were tested on pooled carotid arteries. -ARK expression was assessed in two endothelial cell lines from bovine aorta and aorta isolated from a 12-wk WKY rat. -AR, ₂-AR, and muscarinic responses, but not that to nitroprusside, were depressed in untrained aged vs. young animals. Exercise training restored -AR and muscarinic responses but did not affect vasodilation induced by UK-14304 and nitroprusside. Aged carotid arteries showed reduced -AR number and increased -ARK activity. Training counterbalanced these phenomena and restored -AR density and -ARK activity to levels observed in young rat carotids. Our data indicate that age impairs -AR vasorelaxation in rat carotid arteries through -AR downregulation and desensitization. Exercise restores this response and reverts age-related modification in -ARs and -ARK. Our data support an important role for -ARK in vascular -AR vasorelaxation.

aging; beta-adrenergic receptor; exercise

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