Angiotensinogen and AT1R expression in cerebral and femoral arteries during hindlimb unloading in rats.
BACKGROUND
Studies aimed at elucidating the role of the vascular renin-angiotensin system (RAS) in the mechanism of vascular adaptation to microgravity will also lead to a better understanding of vascular health issues of astronauts during future long-duration spaceflight. The aim of the present study was to elucidate whether the expression of the key components of vascular RAS, angiotensinogen (Ao), and angiotensin II receptor type 1 (AT1R) is differentially regulated in cerebral and hindquarter arteries during simulated microgravity.


METHODS
Tail-suspended hind limb unloading (HLU) for 1 and 4 wk were used to simulate the cardiovascular effect of microgravity. Changes of gene and protein expression of Ao and AT1R in cerebral and femoral arterial tissues were examined by conventional and real-time reverse transcription polymerase chain reaction and Western blot analysis.


RESULTS
After 1 wk of simulated microgravity, there were no significant differences in gene [normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] and protein (normalized to beta-actin) expressions of Ao and AT1R in cerebral and femoral arterial tissues between control and HLU rats. However, after a 4-wk simulated microgravity, as compared with control, the mRNA expressions of Ao, and AT1a and AT1b in cerebral arterial tissue were significantly increased (1.45 +/- 0.14, 1.30 +/- 0.11, and 1.63 +/- 0.22-fold, respectively), and Ao mRNA expression (real-time PCR) and AT1a mRNA expression in femoral arterial tissue were significantly decreased (0.56 +/- 0.05 and 0.71 +/- 0.09-fold, respectively) in HLU rats. After a 4-wk simulated microgravity, protein expressions of Ao and AT1R in cerebral arterial tissue were significantly increased (2.09 +/- 0.55 and 1.38 +/- 0.14-fold, respectively). Whereas in femoral arterial tissue, AT1 protein expression decreased significantly (0.62 +/- 0.06-fold), but that of Ao just showed a trend of decrease.


CONCLUSIONS
Our findings have demonstrated that a mid-term simulated microgravity might up- and down-regulate the gene and protein expressions of Ao and AT1R in cerebral and femoral arterial tissues of rats, suggesting the important role of the vascular RAS in mediating and modulating vascular adaptation during microgravity exposure.
Bao
Jun-Xiang
JX
Department of Aerospace Physiology, Fourth Military Medical University, 17 Changlexi Rd., Xi'an 710032, Shaanxi Province, China.
Zhang
Li-Fan
LF
Ma
Jin
J
D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D002536:Cerebral Arteries / Q000502:physiology; D015536:Down-Regulation; D005263:Femoral Artery / Q000502:physiology; D019417:Hindlimb Suspension / Q000502:physiology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D015854:Up-Regulation
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen