Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Abstract

Modulation of ␤-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats. J Appl Physiol 105: 569 -574, 2008. First published May 29, 2008 doi:10.1152/japplphysiol.01381.2007.-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 (ϩdP/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

Cell Respiration of Rat Cardiomyocytes and Soleus Muscle Fibers under Ultra-Short-Term Antiorthostatic Suspension

“…Short-term effects lead to a bulk-load increase on the heart by cardiopulmonary receptor activation [23]. Yin et al [24] and Cui et al [25] showed that the rats' heart mass and arterial pressure remained at the control level, but pressure in the left ventricle decreased. Baroceptor reflex sensitivity also does not differ after a 14-day suspension [26].…”

Structure and Functional Characteristics of Rat’s Left Ventricle Cardiomyocytes under Antiorthostatic Suspension of Various Duration and Subsequent Reloading

“…At the same time, Yin et al [13] and Cui et al [14] demonstrated that, after 4 weeks of suspension, the heart weight and arterial pressure of rats do not change, while the pressure in the left ventricle decreases. The sensitivity of the baroreceptor reflex after 14 days of suspension also remains unchanged [15].…”

Modulation of intracellular calcium transient in response to β-adrenoceptor stimulation in the hearts of 4-wk-old rats during simulated weightlessness

“…The results suggested that some downstream sites in ␤-adrenoceptor signaling cascades, namely, G s protein/AC/cAMP/ PKA/Ca 2ϩ /contraction, may be impaired in the heart of HLU rats. In our laboratory's previous study (17), we determined G s protein and the function of AC under simulated microgravity. It was shown that the biologically active isoform, G s␣ -small, was not changed after 4 wk of HLU.…”

“…The function of AC, the enzyme activated by the G s protein and, in turn, converts ATP into cAMP, is impaired during weightlessness. We have also documented that weightlessness is associated with reductions in cellular cAMP and impaired AC response to forskolin (17), an activator of AC (12). When facilitated by ␤-adrenoceptor stimulation during excitation and contraction coupling, whether or not downstream Ca 2ϩ cascade during weightlessness is changed warrants study.…”

“…In our laboratory's previous study, we showed that the function of the G s protein, which mediates the action of ␤-adrenoceptor stimulation (7,9,11), is not altered during weightlessness (17). The function of AC, the enzyme activated by the G s protein and, in turn, converts ATP into cAMP, is impaired during weightlessness.…”