The aim of the present work was to obtain insights into the pathophysiology of cardiovascular deconditioning (CVD) induced by tail suspension (TS) in the rat: during TS, when central venous pressure (CVP) has been normalized (E. Martel, P. Champéroux, P. Lacolley, S. Richard, M. Safar, and J. L. Cuche. J. Appl. Physiol. 80: 1390-1396, 1996), and during simulated orthostatism (SO), when transient episodes of
hypotension and
bradycardia are disclosed,
bradycardia with SO represents a response that seems peculiar to the rat compared with humans. According to basic physiology, a reduced activity of the sympathetic system induced by increased CVP was suspected but was not supported by data obtained through spectral analysis of blood pressure (BP) and heart rate (HR) variability or measurements of plasma
catecholamine concentration during TS. Nonetheless, indirect evidence was obtained. During SO, plasma
catecholamine concentration was lower in TS rats than in controls, suggesting a reduced synthesis of
catecholamines, itself secondary to reduced activity of the sympathetic system. Furthermore, after 48 h of TS, the number of binding sites and affinity of alpha-receptors in rat aorta were increased, compatible with a reduced level of
neurotransmitter in the synaptic cleft. A second series of experiments was carried out to study
hypotension and
bradycardia in TS rats during SO.
Hypersensitivity of serotonergic mechanisms was suspected. Two
5-HT3 receptor antagonists (
ondansetron and
MDL-72222) blocked
hypotension and restored
tachycardia, basic features of orthostatic adaptation of the circulatory system. Response to the
5-HT3 receptor agonist was measured through dose-response curves of BP and HR after injection of
2-methylserotonin. After low doses,
hypotension (10 micrograms/kg) and
bradycardia (3 and 10 micrograms/kg) were significantly greater in 48-h TS rats than in controls. Thus CVD in the rat induced by TS appears to implicate at least two mechanisms: reduced activity of the sympathetic system and
hypersensitivity of serotonergic mechanisms.