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.
Ikawa
H
H
Department of Pharmacology, Kinki University School of Medicine, Osaka, Japan.
Suzuki
A
A
D015720:5'-Nucleotidase / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology / Q000209:etiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D004198:Disease Susceptibility; D015536:Down-Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology*; D006974:Hypertension, Malignant / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D015720:5'-Nucleotidase; D007545:Isoproterenol