Alterations of cardiac adrenoceptors and calcium channels subsequent to production of aortic insufficiency in rats.
Aortic insufficiency (AI) was produced in rats by puncturing one of the aortic valves with a plastic rod inserted from the right carotid artery, and the subsequent changes in alpha- and beta-adrenoceptors and Ca2+ channels were investigated by means of radioligand binding assays. The positive inotropic effects of methoxamine (Met), isoproterenol (Iso) and Ca2+ were also examined in isolated left papillary muscles. The ratio of the whole heart weight to body weight in AI rats increased significantly as compared with sham-operated rats from 1 till 8 weeks after operation, showing that a cardiac hypertrophy had occurred due to the volume overload. Maximum binding sites (Bmax) for 3H-prazosin in cardiac ventricular muscles of AI rats significantly increased at 4 weeks and returned to the control level at 8 weeks when the AI was still patent. Bmax for 3H-dihydroalprenolol (3H-DHA) of AI rats significantly increased at 2 and 4 weeks and returned to the control level at 8 weeks. Bmax for 3H-nitrendipine binding of AI rats significantly decreased at 2 weeks and returned to the control level at 4 weeks. Affinities for these bindings, as expressed by values of dissociation constants, showed no significant changes. The sensitivities of papillary muscles to Met and Iso were significantly increased in AI rats at 4 weeks. Plasma immunoreactive alpha-atrial natriuretic polypeptide (alpha-ANP) concentration of AI rats tended to increase from 1 till 3 weeks and returned to the control level at 4 weeks but these changes were not significant. We conclude that the synthesis of new adrenoceptors keeps pace with the hypertrophic process and may even overshoot during a short period.
Yamazaki
T
T
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Uematsu
T
T
Mizuno
A
A
Takiguchi
Y
Y
Nakashima
M
M
D000818:Animals; D001022:Aortic Valve Insufficiency / Q000378:metabolism / Q000503:physiopathology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects*; D006332:Cardiomegaly / Q000503:physiopathology; D004082:Dihydroalprenolol / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009568:Nitrendipine / Q000378:metabolism; D010210:Papillary Muscles / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013997:Time Factors
D015220:Calcium Channels; D011941:Receptors, Adrenergic; D004082:Dihydroalprenolol; D009320:Atrial Natriuretic Factor; D009568:Nitrendipine; D011224:Prazosin