Exercise restores beta-adrenergic vasorelaxation in aged rat carotid arteries

Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H369-74. doi: 10.1152/ajpheart.00019.2003. Epub 2003 Mar 13.

Abstract

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 (10-6 M), and vasodilation was assessed in response to the beta-AR agonist isoproterenol (10-10-3 x 10-8 M), the alpha2-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). 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, alpha2-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Blotting, Western
  • Body Weight / physiology
  • Brimonidine Tartrate
  • Carotid Arteries / growth & development
  • Carotid Arteries / physiology*
  • Cells, Cultured
  • Cytosol / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Isoproterenol / pharmacology
  • Muscle Relaxation / physiology
  • Muscle, Smooth, Vascular / growth & development
  • Muscle, Smooth, Vascular / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type III
  • Nitroprusside / pharmacology
  • Organ Size / physiology
  • Physical Conditioning, Animal / physiology*
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Inbred WKY
  • Receptors, Adrenergic, beta / physiology*
  • Vasodilator Agents / pharmacology
  • omega-N-Methylarginine / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Enzyme Inhibitors
  • Quinoxalines
  • Receptors, Adrenergic, beta
  • Vasodilator Agents
  • Nitroprusside
  • omega-N-Methylarginine
  • Brimonidine Tartrate
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Isoproterenol
  • Acetylcholine