Modulation of intracellular calcium transient in response to beta-adrenoceptor stimulation in the hearts of 4-wk-old rats during simulated weightlessness.
Modulation of intracellular calcium ([Ca(2+)](i)) 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+)](i) 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+)](i) 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+)](i) transient cause the depressed responsiveness of the beta-adrenoceptor stimulation, which may be partially responsible for the depression of cardiac function.
Department of Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
Yan
Y
Cui
Shu-Miao
SM
Zhang
Quan-Yu
QY
Zhang
Rong
R
Fan
Juan
J
Li
Hai-Tao
HT
Guo
Hui
H
Bi
Yue-Min
YM
Wang
Yu-Zhen
YZ
Hu
Qi-Jun
QJ
Zheng
Chun-Hu
CH
Gu
Shi-Qiang
SQ
Yu
Ding-Hua
DH
Yi
Zhi-Chao
ZC
Li
Jian-Ming
JM
Pei
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D019417:Hindlimb Suspension; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D007545:Isoproterenol; D002118:Calcium