Copyright (c) 2004 by the American Physiological Society. 2 Unlike most of other experimental models of congestive heart failure, the volume overload induced by aortocaval shunt (AVS) in rats was found to exhibit enhanced �-adrenoceptor (�-AR) signaling. To study whether the adenylyl cyclase (AC)-G-protein system is involved in such a change, we examined cardiac AC activity and protein content as well as Gs�- and Gi�-activities, protein contents and mRNA levels in both left and right ventricles (LV and RV) at the failing stage (16 weeks post-surgery). The basal and forskolin stimulated AC activities were significantly increased in both LV and RV from the failing hearts; this change was associated with an upregulation of type V/VI AC protein. In contrast to Gpp(NH)p and NaF, the stimulatory effect of isoproterenol on AC was increased in the failing heart. Although Gs�- and Gi�-protein contents in the failing hearts were not altered, mRNA level for Gs � was decreased by 20 % and that for Gi � was increased by 20%. In addition, the activity of Gs�, but not Gi�, as assessed by toxin catalyzed ADP-ribosylation, was significantly decreased in the failing heart. Losarta
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