Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats

Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri Submitted 3 December 2004 ; accepted in final form 9 March 2005 After periods of microgravity or bed rest, individuals often exhibit reduced O 2 max , hypovolemia, cardiac and vascular effects, and autonomic dysfunction. Recently, alterations in expression of vascular and central nervous system NO synthase (NOS) have been observed in hindlimb-unloaded (HU) rats, a model used to simulate physiological effects of microgravity or bed rest. We examined the effects of 14 days of hindlimb unloading on hemodynamic responses to systemic NOS inhibition in conscious control and HU rats. Because differences in NO and autonomic regulation might occur after hindlimb unloading, we also evaluated potential differences in resting autonomic tone and effects of NOS inhibition after autonomic blockade. Administration of nitro- L -arginine methyl ester ( L -NAME; 20 mg/kg iv) increased mean arterial pressure (MAP) to similar levels in control and HU rats. However, the change in MAP in response to L -NAME was less in HU rats, that had an elevated baseline MAP. In separate experiments, atropine (1 mg/kg iv) increased heart rate (HR) in control but not HU rats. Subsequent administration of the ganglionic blocker hexamethonium (30 mg/kg iv) decreased MAP and HR to a greater extent in HU rats. Administration of L -NAME after autonomic blockade increased MAP in both groups to a greater extent compared with intact conditions. However, the pressor response to L -NAME was still reduced in HU rats. These data suggest that hindlimb unloading in rats reduces peripheral NO as well as cardiac parasympathetic tone. Along with elevations in sympathetic tone, these effects likely contribute to alterations in vascular control and changes in autonomic reflex function following spaceflight or bed rest. cardiovascular deconditioning; simulated microgravity; parasympathetic nervous system; sympathetic nervous system; ganglionic blockade Address for reprint requests and other correspondence: P. J. Mueller, Dalton Cardiovascular Research Center, Dept. of Biomedical Sciences, 134 Research Park Drive, Columbia, MO 65211-3300 (E-mail: muellerp{at}missouri.edu )