Modulation of {beta}-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats.
The modulation of beta-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 beta-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 beta-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, Gsalpha (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 beta-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.
Yin
Wen
W
Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Liu
Jin-Cheng
JC
Fan
Rong
R
Sun
Xi-Qing
XQ
Ma
Jin
J
Feng
Na
N
Zhang
Quan Yu
QY
Yin
Zhao
Z
Zhang
Shu-Miao
SM
Guo
Hai-Tao
HT
Bi
Hui
H
Wang
Yue-Min
YM
Sun
Xin
X
Cheng
Liang
L
Cui
Qin
Q
Yu
Shi-Qiang
SQ
Yi
Ding-Hua
DH
Pei
Jian-Ming
JM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001835:Body Weight / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology*; D019417:Hindlimb Suspension / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D018474:Weightlessness Simulation
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol