Vasopressin V₁ receptors contribute to hemodynamic and sympathoinhibitory responses evoked by stimulation of adenosine A_2a receptors in NTS

Abstract

, 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 V1 receptors may contribute to posthemorrhagic hypotension and bradycardia. Both V 1 and A2a 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 A2a 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 (Ϫ95.6 Ϯ 28.3 vs. 51.4 Ϯ 15.7 ͐⌬%), virtually abolished the decreases in HR (Ϫ258.3 Ϯ 54.0 vs. 18.9 Ϯ 57.8 ͐⌬beats/min) and RSNA (Ϫ239.3 Ϯ 47.4 vs. 15.9 Ϯ 36.1 ͐⌬%), and did not affect the increases in pre-ASNA (279.7 Ϯ 48.3 vs. 233.1 Ϯ 54.1 ͐⌬%) evoked by A 2a receptor stimulation. The responses partially returned toward normal values ϳ90 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 A2a 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 IT IS GENERALLY ACCEPTED that among the numerous neuroactive substances operating in the nucleus of the solitary tract (NTS), adenosine, acting via A 2a receptors, and vasopressin, acting via V 1 receptors, play important roles in the mechanisms of cardiovascular control (4 -6, 11, 14 -16, 20 -24, 32, 37, 40, 41, 47). However, the specific physiological roles of NTS adenosine A 2a and vasopressin V 1 receptors remain unclear, and potential interactions between these two neuromodulators have not been studied.Several studies have suggested that the hypotensive action of adenosine in the NTS is mediated mostly via stimulation of presynaptic A 2a receptors and the release of glutamate from afferent terminals and/or from intrinsic NTS interneurons involved in baroreflex transmission (11,23,25,40). However, evidence from our laboratory (31)(32)(33)(34)(35)37) showed that the pattern of regional sympathetic responses evoked by activation...

Adenosine receptors located in the NTS contribute to renal sympathoinhibition during hypotensive phase of severe hemorrhage in anesthetized rats

“…The control, bilateral microinjections of ACF (100 nl) into the NTS tended to decrease MAP, HR, and RSNA (P Ͼ 0.05 vs. 0) and slightly increased pre-ASNA (P ϭ 0.039 vs. 0). These responses were similar to those observed in our previous studies in which unilateral microinjections of the same volumes of ACF were performed (25,26,28,29). Compared with the effect of vehicle, the bilateral microinjections of nonselective adenosine A 1 -and A 2a -receptor antagonist (8-SPT; 1 nmol/100 nl) and selective adenosine A 2a -receptor antagonist (ZM-241385; 40 pmol/100 nl) significantly decreased pre-ASNA but not RSNA (Table 2).…”

“…RSNA increased significantly after selective blockade of NTS A 2a receptors but not after nonselective blockade of both A 1 and A 2a receptors (Table 2). This observation is also consistent with our previous reports showing that selective stimulation of NTS A 2a receptors decreases RSNA, whereas selective stimulation of NTS A 1 receptors increases RSNA (22)(23)(24)(25)(26)(27)(28)(29). Therefore, the effects of blockade of both A 1 and A 2a receptors on RSNA likely canceled each other.…”

“…In addition, the effects of bilateral selective and nonselective blockade of NTS adenosine receptors on resting levels of regional sympathetic nerve activity and hemodynamic variables were assessed. The hemodynamic and regional sympathetic responses to blockade of NTS adenosine-receptor subtypes observed in the present study were consistent with the known responses to stimulation of these receptors observed in our previous studies (22)(23)(24)(25)(26)(27)(28)(29). To our knowledge, this is the first evidence that both A 1 and A 2a adenosine receptors may tonically modulate MAP, HR, RSNA, and pre-ASNA at the level of the NTS.…”

“…The doses of antagonists were similar to those used effectively in previous studies (1,(33)(34)(35). The volume of microinjected antagonists was the same as used in our previous studies where other NTS receptors/mechanisms (glutamatergic, nitroxidergic, or vasopressinergic) were effectively antagonized (25,26,28,29).…”

“…Therefore, the similarities between the patterns of autonomic responses elicited by severe hemorrhage and those to stimulation of adenosine receptors operating in the NTS may be not coincidental but physiologically related. In addition, our most recent studies showed that nitric oxide (NO) and vasopressin operating via V 1 receptors in the NTS contribute significantly to the depressor, cardiac slowing, and sympathoinhibitory responses elicited via selective stimulation of adenosine A 2a receptors in the NTS (28,29). Importantly, both NO and vasopressin operating in the central nervous system contribute to posthemorrhagic hypotension observed in conscious animals (5,10,19,39).…”