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1Department of Emergency, Xijing Hospital; 2Department of Physiology, National Key Discipline of Cell Biology; 3School of Aerospace Medicine, and 4Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China
Submitted 31 December 2007 ; accepted in final form 9 May 2008
The modulation of β-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 β-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dP/dtmax), and diastolic function (–dP/dtmax) 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 β-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 ±dP/dtmax were significantly reduced. The ABP decrease, LVP increase, and ±dP/dtmax in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced single-cell 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 β-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.
simulated weightlessness; β-adrenoceptor; adenylyl cyclase; cyclic adenosine 5'-monophosphate
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