Beta 1- and beta 2-receptors are differentially desensitized in an experimental model of heart failure.
Recent reports suggested that a complex alteration in beta-receptor function occurs in failing human myocardium. We evaluated beta-receptor-subtype activity in an experimental model of monocrotaline (MCT)-induced cardiomyopathy in the rat. Through pulmonary hypertension, MCT causes right ventricular hypertrophy (RVH), either associated with heart failure or not, beta-Receptor function was evaluated in both failing-hypertrophic and hypertrophic hearts in binding studies with [125I]iodocyanopindolol (ICYP) and by measuring adenylate cyclase (AC) activity. In the right failing ventricle, beta 1- but not beta 2-receptor density was decreased. Lesion-associated modifications in the adenylate cyclase system were also observed: isoproterenol- and guanosine 5' [beta, gamma-imido]triphosphate [Gpp(NH)p]-stimulated cyclic AMP formation was reduced in the right failing ventricle, while the cyclic AMP responses to NaF and forskolin were unchanged. On the other hand, no changes in either beta-receptor density or function were found in hypertrophic ventricles. MCT-induced heart failure in the rat is thus associated with a selective decrease of beta 1-receptor density and function. These results suggest that MCT-induced cardiac failure may be an appropriate model in which to investigate heart insufficiency further.
Pelá
G
G
Department of Cardiology, School of Medicine, University of Brescia, Italy.
Missale
C
C
Raddino
R
R
Condorelli
E
E
Spano
P F
PF
Visioli
O
O
D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D001345:Autoradiography; D002303:Cardiac Output, Low / Q000503:physiopathology*; D006332:Cardiomegaly / Q000503:physiopathology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D020120:Iodocyanopindolol; D016686:Monocrotaline; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000502:physiology*
D011763:Pyrrolizidine Alkaloids; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D016686:Monocrotaline; D020120:Iodocyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases