Vasopressin V1 receptors contribute to hemodynamic and sympathoinhibitory responses evoked by stimulation of adenosine A2a receptors in NTS

Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan Submitted 29 September 2005 ; accepted in final form 6 December 2005 Activation of adenosine A 2a receptors in the nucleus of the solitary tract (NTS) decreases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas increases in preganglionic adrenal sympathetic nerve activity (pre-ASNA) occur, a pattern similar to that observed during hypotensive hemorrhage. Central vasopressin V 1 receptors may contribute to posthemorrhagic hypotension and bradycardia. Both V 1 and A 2a receptors are densely expressed in the NTS, and both of these receptors are involved in cardiovascular control; thus they may interact. The responses elicited by NTS A 2a receptors are mediated mostly via nonglutamatergic mechanisms, possibly via release of vasopressin. Therefore, we investigated whether blockade of NTS V 1 receptors alters the autonomic response patterns evoked by stimulation of NTS A 2a receptors (CGS-21680, 20 pmol/50 nl) in -chloralose-urethane anesthetized male Sprague-Dawley rats. In addition, we compared the regional sympathetic responses to microinjections of vasopressin (0.1–100 ng/50 nl) into the NTS. Blockade of V 1 receptors reversed the normal decreases in MAP into increases (–95.6 ± 28.3 vs. 51.4 ± 15.7 %), virtually abolished the decreases in HR (–258.3 ± 54.0 vs. 18.9 ± 57.8 beats/min) and RSNA (–239.3 ± 47.4 vs. 15.9 ± 36.1 %), and did not affect the increases in pre-ASNA (279.7 ± 48.3 vs. 233.1 ± 54.1 %) evoked by A 2a receptor stimulation. The responses partially returned toward normal values 90 min after the blockade. Microinjections of vasopressin into the NTS evoked dose-dependent decreases in HR and RSNA and variable MAP and pre-ASNA responses with a tendency toward increases. We conclude that the decreases in MAP, HR, and RSNA in response to NTS A 2a receptor stimulation may be mediated via release of vasopressin from neural terminals in the NTS. The differential effects of NTS V 1 and A 2a receptors on RSNA versus pre-ASNA support the hypothesis that these receptor subtypes are differentially located/expressed on NTS neurons/neural terminals controlling different sympathetic outputs. nucleus tractus solitarii; purinoceptors; vasopressin V 1 receptor antagonist; adrenal sympathetic nerve; renal sympathetic nerve Address for reprint requests and other correspondence: T. J. Scislo, Dept. of Physiology, Wayne State Univ.