MECHANISMS OF THE CARDIOVASCULAR DECONDITIONING INDUCED BY TAIL SUSPENSION IN THE RAT

The aim of the present work was to obtain insights into the pathophysi ology of cardiovascular deconditioning (CVD) induced by tail suspensio n (TS) in the rat: during TS, when central venous pressure (CVP) has b een normalized (E. Martel, P. Champeroux, P. Lacolley, S. Richard, M. Safar, and J. L. Cuche. J. Appl. Physiol. 80: 1390-1396, 1996), and du ring simulated orthostatism (SO), when transient episodes of hypotensi on and bradycardia are disclosed, bradycardia with SO represents a res ponse that seems peculiar to the rat compared with humans. According t o basic physiology, a reduced activity of the sympathetic system induc ed by increased CVP was suspected but was not supported by data obtain ed through spectral analysis of blood pressure (BP) and heart rate (HR ) variability or measurements of plasma catecholamine concentration du ring TS. Nonetheless, indirect evidence was obtained. During SO, plasm a catecholamine concentration was lower in TS rats than in controls, s uggesting a reduced synthesis of catecholamines, itself secondary to r educed activity of the sympathetic system. Furthermore, after 48 h of TS, the number of binding sites and affinity of oc-receptors in rat ao rta were increased, compatible with a reduced level of neurotransmitte r in the synaptic cleft. A second series of experiments was carried ou t to study hypotension and bradycardia in TS rats during SO. Hypersens itivity of serotonergic mechanisms was suspected. Two 5-HT3 receptor a ntagonists (ondansetron and MDL-72222) blocked hypotension and restore d tachycardia, basic features of orthostatic adaptation of the circula tory system. Response to the 5-HT3 receptor agonist was measured throu gh dose-response curves of BP and HR after injection of 2-methylseroto nin, After low doses, hypotension (16 mu g/kg) and bradycardia (3 and 10 mu g/kg) were significantly greater in 48-h TS rats than in control s. Thus CVD in the rat induced by TS appears to implicate at least two mechanisms: reduced activity of the sympathetic system and hypersensi tivity of serotonergic mechanisms.