Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

Department of Neurological Surgery, University of Medicine and Dentistry New Jersey-New Jersey Medical School, Newark, New Jersey Submitted 18 June 2008 ; accepted in final form 19 August 2008 This study was designed to delineate the medullary and spinal pathways mediating the cardiovascular responses to cold pressor test (CPT) and to identify neurotransmitters in these pathways. Experiments were done in barodenervated, urethane-anesthetized, male Wistar rats. The CPT was performed by immersing the limbs and ventral half of the body of the rat in ice-cold water (0.5°C) for 2 min. CPT elicited an immediate increase in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). Bilateral blockade of ionotropic glutamate receptors (iGLURs) in the rostral ventrolateral medullary pressor area (RVLM) significantly attenuated the CPT-induced responses. Bilateral blockade of -aminobutyric acid (GABA) receptors, but not iGLURs, in the nucleus ambiguus (nAmb) significantly reduced the CPT-induced increases in HR, but not MAP. Blockade of spinal iGLURs caused a significant reduction in CPT-induced increases in MAP and GSNA, whereas the increases in HR were reduced to a lesser extent. Combination of the blockade of spinal iGLURs and bilateral vagotomy or intravenous atropine almost completely blocked CPT-induced tachycardia. Midcollicular decerebration significantly reduced CPT-induced increases in MAP and HR. These results indicated that: 1 ) CPT-induced increases in MAP, HR, and GSNA were mediated by activation of iGLURs in the RVLM and spinal cord, 2 ) activation of GABA receptors in the nAmb also contributed to the CPT-induced tachycardic responses, and 3 ) brain areas rostral to the brain stem also participated in the CPT-induced pressor and tachycardic responses. arterial pressure; barodenervation; ionotropic glutamate receptors; nucleus ambiguus; sympathetic nerve activity Address for reprint requests and other correspondence: H. N. Sapru, Dept. of Neurological Surgery, MSB H-586, UMDNJ-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103 (e-mail: sapru{at}umdnj.edu )