Department of Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
J Appl Physiol (1985). 2010 Apr;108(4):838-44. doi: 10.1152/japplphysiol.01055.2009. Epub 2010 Feb 4.
Modulation of intracellular calcium (Ca(2+)) transient in response to beta-adrenoceptor stimulation in the hearts of hindlimb unweighted (HLU) rats during simulated weightlessness has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness. Effects of simulated microgravity on beta-adrenoceptor responsiveness were then studied. Mean arterial blood pressure, left ventricular pressure (LVP), systolic function [maximum positive change in pressure over time (+dP/dt(max))], and diastolic function [maximum negative change in pressure over time (-dP/dt(max))] were monitored during the in vivo experiment. beta-Adrenoceptor density was quantitated by radioactive ligand binding. Single rat ventricular myocyte was obtained by enzymatic dissociation method. +/-dP/dt(max), myocyte contraction, intracellular Ca(2+) transient, and L-type calcium current in response to beta-adrenoceptor stimulation with isoproterenol were measured. Compared with the control group, no significant changes were found in heart weight, body weight, and mean arterial blood pressure, whereas LVP and +/-dP/dt(max) were significantly reduced. LVP and +/-dP/dt(max) were significantly attenuated in the HLU group in response to isoproterenol administration. In the in vitro study, the beta-adrenoceptor density was unchanged. Effects of isoproterenol on electrically induced single-cell contraction and Ca(2+) transient in myocytes of ventricles in HLU rats were significantly attenuated. The enhanced L-type Ca(2+) current elicited by isoproterenol in cardiomyocytes was significantly decreased in the HLU group. The above results indicate that impaired function of L-type Ca(2+) current and decreased Ca(2+) transient cause the depressed responsiveness of the beta-adrenoceptor stimulation, which may be partially responsible for the depression of cardiac function.
模拟失重状态下后肢去重(HLU)大鼠心脏β-肾上腺素受体刺激引起的细胞内钙(Ca(2+))瞬变的调制尚未报道。在本研究中,我们采用大鼠尾部悬吊 4 周来模拟失重。然后研究了模拟微重力对β-肾上腺素受体反应性的影响。在体内实验中监测平均动脉血压、左心室压力(LVP)、收缩功能[压力随时间的最大正变化(+dP/dt(max))]和舒张功能[压力随时间的最大负变化(-dP/dt(max))]。β-肾上腺素受体密度通过放射性配体结合定量。通过酶解分离法获得单个大鼠心室肌细胞。异丙肾上腺素刺激时的 +/-dP/dt(max)、心肌收缩、细胞内Ca(2+)瞬变和 L 型钙电流通过测量。与对照组相比,心脏重量、体重和平均动脉血压无显著变化,而 LVP 和 +/-dP/dt(max)显著降低。HLU 组 LVP 和 +/-dP/dt(max)对异丙肾上腺素的反应明显减弱。在体外研究中,β-肾上腺素受体密度保持不变。异丙肾上腺素对 HLU 大鼠心室肌细胞电诱导的单细胞收缩和Ca(2+)瞬变的影响明显减弱。异丙肾上腺素在 HLU 组中引起的 L 型 Ca(2+)电流增强明显减少。上述结果表明,L 型 Ca(2+)电流功能障碍和Ca(2+)瞬变减少导致β-肾上腺素受体刺激的反应性降低,这可能是心脏功能降低的部分原因。