Mechanisms of the cardiovascular deconditioning induced by tail suspension in the rat

1 Department of Internal Medicine and Institut National de la Santé et de la Recherche Médicale Unit 337, Hôpital Broussais, 75270 Paris; 2 Department of Pharmacology, Centre National de la Recherche Scientifique Unité de Recherche Associée 1482, Hôpital Necker, 75730 Paris; and 3 Centre de Recherches Biologiques, 18800 Baugy, France 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 -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-HT 3 receptor antagonists (ondansetron and MDL-72222) blocked hypotension and restored tachycardia, basic features of orthostatic adaptation of the circulatory system. Response to the 5-HT 3 receptor agonist was measured through dose-response curves of BP and HR after injection of 2-methylserotonin. After low doses, hypotension (10 µg/kg) and bradycardia (3 and 10 µg/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. spectral analysis; plasma catecholamines; -adrenergic receptors; 2-methylserotonin; ondansetron; MDL