Effects of Aging and Drugs on Myocardial β-Adrenergic Receptors in M-SHRSP and SHRSP

Abstract

Myocardial β-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 β-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 β-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 β-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 β-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 β-receptors in 10 and 24 week-old WKY, but did not in SHRSP. The extent of this increase of β-receptors was lower in 24 week-old WKY than in 10 week-old WKY. These results suggest that the decrease of myocardial β-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 β-receptor is impaired in young and aged SHRSP and in aged WKY.

Key Words:

• M-SHRSP
• SHRSP
• myocardial β-adrenergic receptor
• isoproterenol
• chemical sympathectomy
• aging