Age-related changes in adrenergic vasoconstrictor responses of the rat hindlimb

Abstract

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.