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Aging is associated with alterations in β-adrenergic receptor (β-AR) signaling and reduction in cardiovascular responses to β-AR stimulation. Because exercise can attenuate age-related impairment in myocardial β-AR signaling and function, we tested whether training could also exert favorable effects on vascular β-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 (10-6M), and vasodilation was assessed in response to the β-AR agonist isoproterenol (10-10-3 × 10-8M), the α2-AR agonist UK-14304 (10-9-10-6M), the muscarinic receptor agonist ACh (10-9-10-6M), and nitroprusside (10-8-10-5M). β-AR density and cytoplasmic β-AR kinase (β-ARK) activity were tested on pooled carotid arteries. β-ARK expression was assessed in two endothelial cell lines from bovine aorta and aorta isolated from a 12-wk WKY rat. β-AR, α2-AR, and muscarinic responses, but not that to nitroprusside, were depressed in untrained aged vs. young animals. Exercise training restored β-AR and muscarinic responses but did not affect vasodilation induced by UK-14304 and nitroprusside. Aged carotid arteries showed reduced β-AR number and increased β-ARK activity. Training counterbalanced these phenomena and restored β-AR density and β-ARK activity to levels observed in young rat carotids. Our data indicate that age impairs β-AR vasorelaxation in rat carotid arteries through β-AR downregulation and desensitization. Exercise restores this response and reverts age-related modification in β-ARs and β-ARK. Our data support an important role for β-ARK in vascular β-AR vasorelaxation.
Nitroprusside, Acetylcholine; pharmacology; Adrenergic beta-Agonists; Animals; Blotting; Western; Body Weight; physiology; Carotid Arteries; growth /&/ development/physiology; Cells; Cultured; Cytosol; metabolism; Endothelium; Vascular; cytology/physiology; Enzyme Inhibitors; Isoproterenol; Muscle Relaxation; Muscle; Smooth; Nitric Oxide Synthase Type III; Nitric Oxide Synthase; antagonists /&/ inhibitors; Nitroprusside; Organ Size; Physical Conditioning; Animal; Quinoxalines; Rats; Inbred WKY; Receptors; Adrenergic; beta; Vasodilator Agents; omega-N-Methylarginine, Nitric Oxide Synthase Type III, Muscle Relaxation, Blotting, Western, Body Weight, Isoproterenol, Organ Size, Adrenergic beta-Agonists, Acetylcholine, Muscle, Smooth, Vascular, Carotid Arteries, Cytosol, Brimonidine Tartrate, Physical Conditioning, Animal, Quinoxalines, Animals, Endothelium, Vascular, Enzyme Inhibitors, Nitric Oxide Synthase, Cells, Cultured
Nitroprusside, Acetylcholine; pharmacology; Adrenergic beta-Agonists; Animals; Blotting; Western; Body Weight; physiology; Carotid Arteries; growth /&/ development/physiology; Cells; Cultured; Cytosol; metabolism; Endothelium; Vascular; cytology/physiology; Enzyme Inhibitors; Isoproterenol; Muscle Relaxation; Muscle; Smooth; Nitric Oxide Synthase Type III; Nitric Oxide Synthase; antagonists /&/ inhibitors; Nitroprusside; Organ Size; Physical Conditioning; Animal; Quinoxalines; Rats; Inbred WKY; Receptors; Adrenergic; beta; Vasodilator Agents; omega-N-Methylarginine, Nitric Oxide Synthase Type III, Muscle Relaxation, Blotting, Western, Body Weight, Isoproterenol, Organ Size, Adrenergic beta-Agonists, Acetylcholine, Muscle, Smooth, Vascular, Carotid Arteries, Cytosol, Brimonidine Tartrate, Physical Conditioning, Animal, Quinoxalines, Animals, Endothelium, Vascular, Enzyme Inhibitors, Nitric Oxide Synthase, Cells, Cultured
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