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Simulated microgravity alters vascular alpha-actin, myosin, and heavy caldesmon.     S. Hwang,  N. Goraya, V. Willis, J. Chan, D. Miao, A. Ali, and R.E. Purdy.   Dept. of Pharmacology, University of California, Irvine, CA, USA

   Astronauts undergo cardiovascular deconditioning during space travel. On return to gravity, they experience orthostatic intolerance. Orthostatic intolerance is characterized by lightheadedness, dizziness, palpitations, and even syncope on standing. Chronic orthostatic intolerance syndrome also afflicts approximately 500,000 Americans.  One mechanism underlying orthostatic intolerance is vascular hyporesponsiveness, an effect of both real and simulated microgravity.  Our goal was to investigate the effect of microgravity on the protein expression of the myofilament proteins alpha-actin, myosin light chain 20 (MLC-20), and myosin heavy chain (MHC), and the myofilament binding proteins heavy caldesmon, calponin, and alpha tropomyosin in rat aortic smooth muscle.  Microgravity was simulated by hindlimb unweighting (HU) in Wistar rats, and after 20 days of HU treatment, abdominal aortas were isolated from both control and HU rats.  Lysates were prepared and western analysis was performed to quantify relative protein levels.  Western blots revealed a HU-induced downregulation of alpha-actin, MLC-20, and MHC and an upregulation of heavy caldesmon in the abdominal aorta. Calponin and alpha tropomyosin levels were not different between Control and HU. It is hypothesized that HU-induced decrease in contractile myofilaments (alpha actin, MLC-20, MHC) plus the increase in the actin binding protein, heavy caldesmon, could contribute to the vascular hyporesponsiveness observed in HU treated arteries. Decrease in heavy caldesmon, calponin and alpha tropomyosin occur during vascular smooth muscle dedifferentiation.  Thus, these proteins are used as markers of classical phenotype change.  Because the levels of these proteins were either unchanged or increased (heavy caldesmon), the present results suggest that the decrease in alpha actin and light and heavy chain myosin were not the consequence of vascular dedifferentiation. 

(Supported by NASA NNA04CK29G)