Submitted on December 31, 2007
Accepted on May 9, 2008
Modulation of 
-adrenoceptor signaling in the hearts of 4 weeks simulated weightlessness rats
Wen Yin1, Jin-Cheng Liu2, Rong Fan, Xi-Qing Sun, Jin Ma, Na Feng, Quan-Yu Zhang, Zhao Yin, Shu-Miao Zhang, Hai-Tao Guo, Hui Bi, Yue-Min Wang, Xin Sun, Liang Cheng, Qin Cui, Shi-Qiang Yu, Ding-Hua Yi3, and Jian-Ming Pei4*
1 Department of Emergency,Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
2 Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
3 Department of Cardiac Surgery, xi'an, Shaanxi, China
4 Department of Physiology, Fourth Military Medical University, xi'an, Shaanxi, China
* To whom correspondence should be addressed. E-mail: jmpei8{at}fmmu.edu.cn.
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 wks 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 (+dp/dtmax), and diastolic function (-dp/dtmax) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by 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 to 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, Gsa (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.
