Role of alpha 1-adrenoceptor activity in progression of cardiac hypertrophy in guinea pig hearts with pressure overload.
To elucidate the role of alpha 1- and beta-adrenergic activities in pressure overload hypertrophy, changes of alpha 1- and beta-adrenoceptors were measured by radioligand binding assay, and the preventive effects of alpha 1- and beta-adrenoceptor blockade on cardiac hypertrophy were assessed in guinea pigs after aortic banding. Five days after banding, dry weight of left ventricle had not increased, though wet weight increased due to marked intercellular oedema. In this period, the maximum binding capacity of [3H] prazosin increased to 31.1 (SEM 2.2) fmol.mg-1 from (sham operation) 17.0(2.1) fmol.mg protein-1, p less than 0.01, whereas the maximum binding capacity of [3H]dihydroalprenolol did not increase: 143(16) fmol.mg-1 (banded) v 153(13) fmol.mg-1 (sham). Three weeks after aortic banding, the maximum binding capacity of both ligands increased to 45.6(5.5) fmol.mg-1 and 232(21) fmol.mg-1, respectively, accompanied by a significant increase in left ventricular dry weight, from 0.46(0.02) mg.g-1 (sham) to 0.62(0.08) mg.g-1 (banded), p less than 0.01. Continuous subcutaneous administration of the alpha 1-blocker bunazosin (0.1 mg.kg-1.d-1) significantly attenuated the increase in left ventricular dry weight whereas the beta-blocker propranolol (5 mg.kg-1.d-1) did not: 0.55(0.03) v 0.66(0.04) mg.g-1 respectively, after 3 weeks. These results show that pressure overload elicited an increase in myocardial alpha 1-adrenoceptors before the onset of cardiac hypertrophy, and that an alpha 1-blocker could prevent the development of hypertrophy in the pressure overloaded heart.
Tamai
J
J
First Department of Medicine, Osaka University School of Medicine, Japan.
Hori
M
M
Kagiya
T
T
Iwakura
K
K
Iwai
K
K
Kitabatake
A
A
Watanabe
Y
Y
Yoshida
H
H
Inoue
M
M
Kamada
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D006332:Cardiomegaly / Q000503:physiopathology*; D003250:Constriction; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000032:analysis; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000032:analysis / Q000473:pathology; D009638:Norepinephrine / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D009638:Norepinephrine