Adaptations of arterial and venous systems following muscular inactivity

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When there is reduced daily postural challenge (as after prolonged bed rest), the cardiovascular system does not respond adequately to postural change from lying down to the upright position, and hypotension, dizziness and fainting may occur. We wish to use the hind limb unweighting (HLU) rat model to investigate the cause of circulatory derangement associated with muscular inactivity. HLU involves suspending a rat via a tail harness at a head-down tilt position to reduce hindquarter muscular activity. The rats can move around freely on the front limbs. We want to know if there is excessive production of nitric oxide (NO) in the hindquarter of the rat, and if blockade of NO production will alleviate the circulatory abnormality. NO is a strong dilator of blood vessels, and too much of it can cause low blood pressure as well as reduce blood flow to the brain thereby causing dizziness and/or fainting. We have found that following 2 weeks of HLU, vascular bed at the hindquarter of the rat, relative to those in the neck and head region, have impaired vasoconstriction. We want to find out if the impairment is related to increased production of NO or impairment of blood pressure controlling systems such as the sympathetic nervous system, and the renin-angiotensin system. This proposed study is aim to increase our understanding of the mechanism by which vascular function is altered by inactivity.