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Am J Physiol Heart Circ Physiol 291: H2453-H2461, 2006. First published June 2, 2006; doi:10.1152/ajpheart.00158.2006
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Adenosine receptors located in the NTS contribute to renal sympathoinhibition during hypotensive phase of severe hemorrhage in anesthetized rats

Tadeusz J. Scislo and Donal S. O'Leary

Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan

Submitted 10 February 2006 ; accepted in final form 30 May 2006

Stimulation of nucleus of the solitary tract (NTS) A2a-adenosine receptors elicits cardiovascular responses quite similar to those observed with rapid, severe hemorrhage, including bradycardia, hypotension, and inhibition of renal but activation of preganglionic adrenal sympathetic nerve activity (RSNA and pre-ASNA, respectively). Because adenosine levels in the central nervous system increase during severe hemorrhage, we investigated to what extent these responses to hemorrhage may be due to activation of NTS adenosine receptors. In urethane- and {alpha}-chloralose-anesthetized male Sprague-Dawley rats, rapid hemorrhage was performed before and after bilateral nonselective or selective blockade of NTS adenosine-receptor subtypes [A1- and A2a-adenosine-receptor antagonist 8-(p-sulfophenyl)theophylline (1 nmol/100 nl) and A2a-receptor antagonist ZM-241385 (40 pmol/100 nl)]. The nonselective blockade reversed the response in RSNA (–21.0 ± 9.6 {Delta}% vs. +7.3 ± 5.7 {Delta}%) (where {Delta}% is averaged percent change from baseline) and attenuated the average heart rate response (change of –14.8 ± 4.8 vs. –4.4 ± 3.4 beats/min). The selective blockade attenuated the RSNA response (–30.4 ± 5.2 {Delta}% vs. –11.1 ± 7.7 {Delta}%) and tended to attenuate heart rate response (change of –27.5 ± 5.3 vs. –15.8 ± 8.2 beats/min). Microinjection of vehicle (100 nl) had no significant effect on the responses. The hemorrhage-induced increases in pre-ASNA remained unchanged with either adenosine-receptor antagonist. We conclude that adenosine operating in the NTS via A2a and possibly A1 receptors may contribute to posthemorrhagic sympathoinhibition of RSNA but not to the sympathoactivation of pre-ASNA. The differential effects of NTS adenosine receptors on RSNA vs. pre-ASNA responses to hemorrhage supports the hypothesis that these receptors are differentially located/expressed on NTS neurons/synaptic terminals controlling different sympathetic outputs.

nucleus of the solitary tract; tonic activity of purinergic receptors; hypotensive hemorrhage; adrenal sympathetic nerve; renal sympathetic nerve



Address for reprint requests and other correspondence: T. J. Scislo, Dept. of Physiology, Wayne State Univ. School of Medicine, 540 East Canfield Ave., Detroit, MI 48201 (e-mail: tscislo{at}med.wayne.edu)




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