Prolonged exposure to bed rest or microgravity in humans, results in a number of adverse cardiovascular consequences, leading to cardiovascular deconditioning. Rat hindlimb unloading (HU) is an animal model of cardiovascular deconditioning and results in similar cardiovascular consequences including orthostatic intolerance. Blunted sympathetic vasoconstriction appears to contribute to orthostatic intolerance after bedrest or space flight. Studies in HU rats suggest that reflex activation of the sympathetic nervous system in response to hypotensive stimuli is blunted following cardiovascular deconditioning. It is unclear whether these alterations in autonomic function represent a chronic adaptation to microgravity or bedrest or are due to the acute response to return to a 1 G environment or resumption of an upright posture, respectively. The specific mechanisms that contribute to baroreflex dysfunction following deconditioning are unknown, but a number of factors are likely candidates. Activation of cardiopulmonary receptors, due to the cranial shift in blood volume during the HU period, could account for the changes in arterial baroreflex function. In addition, changes in circulating humoral agents acting at circumventricular organs, specifically vasopressin acting at the area postrema, could also produce the observed changes in baroreflex control of sympathetic activity following cardiovascular deconditioning. Furthermore, the attenuated sympathoexcitation appears to be due to altered central nervous system integration of baroreceptor afferent activity and likely involves changes in the rostral ventrolateral medulla (RVLM). The RVLM is critically important in control of the sympathetic nervous system. The diminished reflex-sympathoexcitation following deconditioning appears to be due in part to enhanced inhibition of the RVLM but could also be mediated by a reduction in excitatory influences at the RVLM. The proposed studies will investigate the factors contributing to alterations in arterial baroreflex function due to HU and the mechanisms that mediate those changes. SPECIFIC AIMS: 1. To examine mechanisms contributing to blunted arterial baroreflex control of sympathetic nerve activity in conscious hindlimb unloaded rats. 2. To evaluate mechanisms contributing to diminished activation of the RVLM after hindlimb unloading. 3. To determine whether blunted reflex control of sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unloading is due to chronic adaptations or responses to return to the horizontal position.