Effects of aging and drugs on myocardial beta-adrenergic receptors in M-SHRSP and SHRSP.

Myocardial beta-adrenergic receptors were measured in membrane fractions from malignant SHRSP (M-SHRSP), SHRSP and WKY at different ages using [3H]-dihydroalprenolol (DHA) as a radioligand. The effects of isoproterenol (ISP) and chemical sympathectomy (6-hydroxydopamine treatment) on myocardial beta-receptors were also investigated in 10 and 24 week-old SHRS and WKY to examine the effects of hypertension and aging on receptor regulation. The number of myocardial beta-receptors in M-SHRSP at 4 weeks of age (W) and 10 W were significantly lower than those in age-matched SHRSP and WKY. In addition, the values in SHRSP at 4 and 10 W were significantly lower than those in age-matched WKY, but the numbers in SHRSP at 1, 24 and 48-54 W were not significantly different from age-matched WKY. The dissociation constant and activity of 5'-nucleotidase, which is a marker enzyme of cell membrane, were not significantly different among the three groups. ISP treatment significantly reduced the numbers of myocardial beta-receptors in 10 week-old SHRSP and 10 and 24 week-old WKY, but did not in 24 week-old SHRSP. The extent of this decrease of beta-receptors was lower in 10 week-old SHRSP than in 10 week-old WKY, and it was also lower in 24 week-old WKY than 10 week-old WKY. 6-Hydroxydopamine treatment significantly increased the number of myocardial beta-receptors in 10 and 24 week-old WKY, but did not in SHRSP. The extent of this increase of beta-receptors was lower in 24 week-old WKY than in 10 week-old WKY. These results suggest that the decrease of myocardial beta-receptor numbers in 4 and 10 week-old M-SHRSP and SHRSP does not appear to be genetically determined, but rather is caused by accelerated sympathetic activity, and that the regulation of myocardial beta-receptor is impaired in young and aged SHRSP and in aged WKY.