Differential changes of myocardial beta-adrenoceptor subtypes and G-proteins in dogs with right-sided congestive heart failure.
We have shown previously in dogs with right heart failure that the reduction of myocardial beta-adrenoceptor density occurs only in the failing right ventricle, while cardiac inotropic responses to beta-adrenergic stimulation are reduced in both the right and left ventricles. The purpose of the present study was to determine whether a post-receptor defect in the guanine nucleotide-binding regulatory proteins (G-proteins) existed which would explain, at least in part, the adrenergic subsensitivity in both ventricles of the heart failure dogs. Using both immunoblotting technique and the bacterial toxin-mediated ADP ribosylation assays, we found that the stimulatory G-protein (Gs) was reduced in both ventricles of the heart failure dogs. In contrast, there were no changes in the inhibitory G-protein (Gi). In addition, receptor subtype analysis showed that only beta(1)-adrenoceptors were reduced in the failing right ventricle of the heart failure animals. This study demonstrated that the reduction of beta-adrenoceptors in right heart failure was chamber-specific whereas the reduction of Gs was non-selective, occurring in both ventricles of right heart failure dogs. The findings further suggest that the reduction of Gs probably was caused by systemic neurohormonal activation, independent of local ventricular stress.
Lai
L P
LP
Department of Medicine, University of Rochester Medical Center, NY 14642, USA.
Suematsu
M
M
Elam
H
H
Liang
C S
CS
D000244:Adenosine Diphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002772:Cholera Toxin / Q000378:metabolism; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D037342:Pertussis Toxin; D010759:Phosphorus Isotopes; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D010759:Phosphorus Isotopes; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases