We haverecently reported enhanced levels of G
i proteins ingenetic and other experimentally induced models of hypertension, whereas the levels of G
s were decreased in hypertensiverats expressing cardiac hypertrophy. The present studies wereundertaken to investigate whether the decreased levels ofG
s are associated with cardiac hypertrophy per se andused an aortocaval fistula (AV shunt; volume overload) rat model thatexclusively expresses cardiac hypertrophy. Cardiac hypertrophy inSprague-Dawley rats (200-250 g) was induced under anesthesia, and,after a period of 10 days, the hearts were used for adenylyl cyclaseactivity determination, protein quantification, and mRNA leveldetermination. A temporal relationship between the expression ofG
s proteins and cardiac hypertrophy was also examined on
days 2, 3, 7, and
10 after induction of AV shuntin the rat. The heart-to-body-weight ratio (mg/g) was significantlyincreased in AV shunt rats after 3, 7, and 10 days of induction of AVshunt compared with sham-operated controls, whereas arterial bloodpressure was not different between the two groups. Guanosine5'-
O-(3-thiotriphosphate) (GTPS) stimulated adenylylcyclase activity in a concentration-dependent manner in heart membranesfrom both groups; however, the degree of stimulation was significantlydecreased in AV shunt rats. In addition, the stimulatory effects ofisoproterenol were also diminished in AV shunt rats compared withcontrol rats, whereas glucagon-stimulated adenylyl cyclase activity wasnot different in the two groups. The inhibitory effects of oxotremorine(receptor-dependent G
i functions) and low concentrations ofGTPS on forskolin-stimulated adenylyl cyclase activity(receptor-independent G
i functions) were not different inthe two groups. In addition forskolin and NaF also stimulated adenylylcyclase activity to a lesser degree in AV shunt rats compared withcontrol rats. The levels of G
i-2 and G
i-3proteins and mRNA, as determined by immunoblotting and Northernblotting, respectively, were not different in both groups; however, thelevels of G
s45 andG
s47, and not ofG
s52, proteins were significantly decreasedin AV shunt rats by
days 7 and
10 compared withcontrol rats, whereas no change was observed on
days 2 and
3 after induction of AV shunt. These results suggest thatthe decreased expression of G
s proteins may not be thecause but the effect of hypertrophy and that the diminishedresponsiveness of adenylyl cyclase to GTPS, isoproterenol, NaF, andforskolin in hearts from AV shunt rats may partly be due to thedecreased expression of G
s. It can be concluded fromthese studies that the decreased expression of G
s may beassociated with cardiac hypertrophy and not with arterial hypertension.
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