Changes In Vascular, Myocardial, And Renal Tissue Renin-angiogensin Systems Due To Simulated Weightlessness In Rats

The influence of real/simulated weightlessness involves many organs and systems. For gaining a clear understanding on postflight cardiovascular dysfunction and developing effective countermeasures, it is important to elucidate how the physiological adaptation to weightlessness happens. Recent observations during spaceflight or ground-based simulation studies have both suggested that hypovolemia and adaptational changes in vessels and myocardium are important mechanisms responsible for postflight orthostatic intolerance. Previous findings from our laboratory have demonstrated that simulated weightlessness may result in atrophic changes with depressed vasoconstrictor responsiveness in hindquarter vessels, and hypertrophic changes with enhanced vasoconstrictor responsiveness in cerebral arteries of rats. Simul-ated weightlessness also can induce depressed myocardial contractility with changes in myocardial collagens similar to these in aging rat heart. Up to now, we do not know clearly how these changes happen. Because the renin-angiotensin system (RAS) participate in not only humoral regulation of body fluid and systemic blood pressure but also structural and functional autoregulations in many tissues, we speculated that it may play a pivotal role in arterial structural and functional autoregulations, myocardial and renal adaptational changes due to simulated weightlessness. Therefore, we designed the present experiment using tail-suspended rat model to simulate the effects of weightlessness and the reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to examine changes in gene and protein expressions of principal components of local RAS (L-RAS) in vascular, myocardial and renal tissues of rats after 1- or 4-wk simulated weightlessness. The main findings of the present work are as follows:1. Changes in gene and protein expressions of principal L-RAS components in arterial tissues of simulated weightless rats Gene expressions of enzymatic components of L-RAS changed differentially in cerebral and hindquarter arterial tissues of 1-wk simulated weightless rats: mRNA expression of renin increased in basilar arterial tissue, whereas the mRNA expression of angiotensin converting enzyme (ACE) decreased significantly in femoral arterial tissue. However, in 4-wk simulated weightless rats, the differential changes were manifested mainly in angiotensinogen (AGT) and angiotensin II (Ang II) receptor, AT1: in basilar arterial tissue, the mRNA expressions of two subtypes of AT1 receptor (AT1a and AT1b) increased significantly, and the protein expressions of AGT and AT1also increased significantly; contrarily, in femoral arterial tissue, mRNA expression of AT1a decreased significantly; protein expression of AGT in femora! arterial and anterior rnesenteric arterial and its branching tissues showed a tendency of decrease, whereas in both arterial tissues, protein expression of AT1 decreased significantly. These findings support our hypothesis that the L-RAS within the arterial wall tissues might play a pivotal role in the differential functional and structural adaptations of vessels from different anatomic regions. Furthermore, the characteristic time course of changes in expressions of different L-RAS components was shown in the present study. 2. Changes in gene and protein expressions of principal L-RAS components in myocardial tissue of simulated weightless rats In the present study, the gene expressions of AGT, ACE, AT1aand AT1b, but not renin and Ang II type 2 receptor, AT2 were detected in the free wall tissue of left ventricular myocardium of normal Sprague-Dawley rat. There were no significant differences in mRNA expressions of AGT, ACE, AT1a or AT1b between 1-wk tail-suspended and control rats. However, after 4-wk simulated weightlessness, the mRNA expression of AT1a in left-ventricular free-wall myocardial tissue increased significantly, with its protein expression showing a non-significant change. Furthermore, in 4-wk simulated weightless rats, the mRNA exp...