Influence of age on control of norepinephrine release from the rat tail artery.
Stimulation-evoked norepinephrine release from the rat tail artery increases with age; therefore, the sensitivity of prejunctional alpha-2 adrenergic receptors to antagonists and agonists was compared in perfused tail arteries from Fischer-344 rats, aged 6 and 20 months. The increase in endogenous fractional norepinephrine release produced by blockade of alpha-2 adrenergic receptors with submaximal concentrations of either yohimbine or idazoxan was significantly greater in 6-month-old animals as compared to 20 months; however, the effect of a maximal concentration of idazoxan was not significantly different. Inhibition of norepinephrine release by the alpha-2 receptor agonist UK14304 was reduced in 20-month-old animals compared to 6 months. In contrast, there were no age-related differences in inhibition of contractile responses to nerve stimulation by the prejunctionally acting dopamine D2 agonist, N-0923. These data suggest that age-related changes in the sensitivity of prejunctional alpha-2 receptors to agonists and antagonists may not reflect any fundamental alteration in the function of this receptor system, but may be related to competition between alpha-2 agonists or antagonists and increased biophase concentrations of norepinephrine. This conclusion is supported by lack of an age-related change in function of prejunctional dopamine D2 receptors. Persistence of age-related increases in norepinephrine release when alpha-2 adrenergic receptors are fully blocked may reflect an alteration in other fundamental mechanisms that control norepinephrine release.
Department of Pharmacology, College of Medicine, University of California, Irvine.
J
J
Buchholz
H
H
Tsai
D
D
Friedman
S P
SP
Duckles
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000187:drug effects; D013623:Tail; D015016:Yohimbine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D011810:Quinoxalines; D011954:Receptors, Dopamine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D009638:Norepinephrine; D019329:Idazoxan