Proposed role of the paraventricular nucleus in cardiovascular deconditioning

Aim: Cardiovascular deconditioning occurs in individuals exposed to prolonged spaceflight or bedrest and is associated with the development of orthostatic intolerance. Although the precise mechanisms remain to be fully elucidated, astronauts returning from space or bedrest patients returning to normal upright posture present with decreases in plasma volume and alterations in autonomic function. The hindlimb unloaded (HU) rat has been a useful model to study the effects of cardiovascular deconditioning as it mimics many of the changes that occur after spaceflight and bedrest. Results: Experiments performed in HU rats suggest that cardiovascular deconditioning attenuates baroreflex mediated sympathoexcitation and enhances cardiopulmonary receptor mediated sympathoinhibition. These alterations appear to be due to changes in the central nervous system and may contribute to the pre disposition towards orthostatic intolerance associated with cardiovascular deconditioning. The paraventricular nucleus (PVN) of the hypothalamus is important in basal and reflex control of sympathetic outflow. Recent evidence suggests that nitric oxide (NO) is an important inhibitory neurotransmitter in the PVN and that alterations in nitroxidergic transmission in the PVN may be involved in elevated sympathetic tone in certain disease states. Conclusion: Based on evidence from other laboratories and published and preliminary data from our own laboratories, this review proposes a role for the PVN in cardiovascular deconditioning. In particular, we discuss the hypothesis that increased NO in the PVN contributes to the altered cardiovascular reflexes observed following deconditioning and how these reflexes may be related to the orthostatic intolerance observed after prolonged spaceflight or bedrest.