Age-related decline in adrenergic responsiveness of the kidney, heart and aorta of male rats.

Studies were undertaken to evaluate the rate of loss in beta-adrenergic responsiveness in the kidney, heart and thoracic aorta in aging male rats. The dipsogenic response to isoproterenol (15 micrograms/kg B.W.) was reduced by 53 and 78% in middle-aged (12 to 13 months) and old (24 to 25 months) versus young (4 to 5 month) rats. In contrast, the drinking response to angiotensin I was unaltered with increasing age, indicating that the decline in B-response was not due to an alteration in the processing of or response to angiotensin. The chronotropic response of the heart to isoproterenol (5 micrograms/kg B.W.) was only moderately decreased by middle-age but was reduced by 69% in old versus young rats. Similarly, the isoproterenol-induced relaxation of aortic rings, in vitro was unchanged at 12 to 13 months of age but was severely diminished at 24 to 25 months of age. Thus the decline in beta-adrenergic responsiveness which accompanies the aging process appears to occur at different rates in several peripheral tissues. In vitro, aortic rings exhibited an age-related decline in contractile response to increasing dose of potassium chloride (KCL) and norepinephrine (NE). Maximum contractility in response to KCl was reduced by middle-age and declined further by 24 to 25 months of age. Similarly, the contractile response of aortic rings to low doses of NE (5 X 10(-10) and 1 X 10(-9)M) was significantly reduced at both middle and old age. Thus, both alpha-adrenoceptor mediated as well as non-receptor mediated aortic contractility are reduced progressively with increasing post-maturational age.