Exercise restores [beta]-adrenergic vasorelaxation in aged rat carotid arteries

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