AJP - Heart and Circulatory Physiology, Vol 253, Issue 6 1566-H1572, Copyright © 1987 by American Physiological Society
Age-related changes in adrenergic vasoconstrictor responses of the rat hindlimb
R. K. Handa and S. P. Duckles
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
Vascular adrenergic responses were examined in the hindlimb perfused with
blood at constant flow using pentobarbital-anesthetized male Fischer 344
rats aged 6, 12, 20, and 24 mo. The increase in hindlimb perfusion pressure
to lumbar sympathetic nerve stimulation was significantly smaller in 20-
and 24-mo-old rats than in younger animals, whereas vasoconstrictor
responses to intraarterial administration of norepinephrine,
L-phenylephrine, and methoxamine were reduced only in the 24-mo-old
animals. Thus neurogenic vasoconstriction in the hindlimb is reduced at 20
mo of age, whereas there is a more generalized postjunctional loss of
adrenergic responsiveness at 24 mo. In the presence of the
beta-adrenoceptor antagonist, propranolol, vasoconstrictor responses to
exogenous norepinephrine did not differ when 12- and 20-mo-old animals were
compared. Furthermore, in the presence of propranolol the nerve-mediated
rise in hindlimb perfusion pressure also did not differ in 12- and
20-mo-old rats. Blockade of neuronal norepinephrine uptake with cocaine
produced a greater potentiation of vasoconstrictor responses to both nerve
stimulation and exogenous norepinephrine in the older rats. Therefore, the
reduced nerve-mediated vasoconstriction in 20-mo-old rats may be due to
neuronal activation of beta-adrenoceptors as well as enhanced neuronal
norepinephrine reuptake.
