The impact of aging on adrenergic receptor function: clinical and biochemical aspects.
From this discussion, several conclusions can be drawn. First, with advancing age there is a decrease in cardiovascular responsiveness and, more specifically, there is a decrease in catecholamine-stimulated chronotropic and inotropic responses. This decreased function has its biochemical correlate in the observation that cyclic AMP levels are decreased in response to isoproterenol infusion in cells or tissues derived from aged organisms. Second, although most work on human circulating cells suggests that beta-adrenergic receptor densities are unchanged, measurements of beta-adrenergic receptor concentrations in various cells from various animals (predominantly rats) have yielded conflicting results. Some of this disparity could be due to the observation that local concentrations of norepinephrine, such as those found intramyocardially, may be very different from those in circulating plasma. Indeed, whereas circulating norepinephrine levels tend to rise with age, the intramyocardial norepinephrine levels tend to fall with senescence. Thus, circulating lymphocytes may or may not be an appropriate model to reflect the catecholamine milieu to which other tissues may be exposed. Accordingly, a note of caution must be entered in terms of extrapolating findings regarding the levels of human lymphocyte beta-adrenergic receptors and cyclic AMP activity to those found, for example, in the human heart. Furthermore, it is likely that age-related changes in adrenergic function may be the result of changes in coupling of receptors to the adenylate cyclase system, as suggested by Feldman and co-workers, and/or changes in steps distal to cyclase activation, as suggested by Guarnieri and colleagues.(ABSTRACT TRUNCATED AT 250 WORDS)
Heinsimer
J A
JA
Lefkowitz
R J
RJ
D000262:Adenylyl Cyclases / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000187:drug effects; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008958:Models, Molecular; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases