Modulation of ␤-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats. The modulation of ␤-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on ␤-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function

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... P/dt max), and diastolic function (ϪdP/dt max) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to ␤-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and ϮdP/dt max were significantly reduced. The ABP decrease, LVP increase, and ϮdP/dt max in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced singlecell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gs␣ (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes ␤-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function. simulated weightlessness; ␤-adrenoceptor; adenylyl cyclase; cyclic adenosine 5Ј-monophosphate