[The adrenergic beta system in an experimental model of heart failure].
Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.
Pelà
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Cattedra di Cardiologia, Università degli Studi, Brescia.
Raddino
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R
Missale
C
C
Condorelli
E
E
Spano
P F
PF
Visioli
O
O
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005260:Female; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases
Sistema beta-adrenergico in un modello sperimentale di scompenso cardiaco.