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Related Experiment Videos

Aging: changes in cardiac alpha 1-adrenoceptor responsiveness and expression.

K A Kimball1, L E Cornett, E Seifen

  • 1Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.

European Journal of Pharmacology
|November 13, 1991
PubMed
Summary

Aging reduces the heart's response to alpha-1 adrenergic stimulation. This decline in responsiveness is linked to fewer alpha-1 adrenoceptors in the heart muscle, as shown in aging rats.

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Area of Science:

  • Cardiovascular Physiology
  • Aging Research
  • Molecular Cardiology

Background:

  • Cardiac muscle responsiveness to beta-adrenoceptor agonists diminishes with age.
  • Limited knowledge exists on how aging affects alpha-adrenoceptor-mediated myocardial actions.

Purpose of the Study:

  • To investigate aging-dependent changes in alpha-1 adrenoceptor function and expression in rat cardiac muscle.
  • To assess the inotropic response to methoxamine, alpha-1 adrenoceptor density, and mRNA levels.

Main Methods:

  • Isolated cardiac preparations from F344 rats of 4, 14, and 25 months of age were used.
  • Inotropic responses to methoxamine were measured in right ventricular strips.
  • Alpha-1 adrenoceptor characteristics were assessed using [3H]prazosin binding.

Related Experiment Videos

  • Alpha-1 adrenoceptor mRNA levels were quantified via Northern blot analysis.

    • Main Results:

    • A significant aging-associated decline in the maximum positive inotropic effect of methoxamine was observed.
    • Ventricular sarcolemmal membranes showed a progressive reduction in alpha-1 adrenoceptor number with age.
    • Steady-state levels of alpha-1 adrenoceptor mRNA decreased significantly with advancing age.

    Conclusions:

    • The aging-related decline in alpha-1 adrenergic responsiveness in rat ventricular muscle is partly mediated by decreased alpha-1 adrenoceptor density.
    • Reduced alpha-1 adrenoceptor expression at both protein and mRNA levels contributes to diminished cardiac function in aging.