Stimulation of NTS A₁adenosine receptors differentially resets baroreflex control of regional sympathetic outputs

Abstract

Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal > renal >/= lumbar) evoked by stimulation of A(1) adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A(1) receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activity. In urethane-chloralose-anesthetized male Sprague-Dawley rats (n = 65) we compared baroreflex-response curves (iv nitroprusside and phenylephrine) evoked before and after bilateral microinjections into the NTS of A(1) adenosine receptor agonist (N(6)-cyclopentyladenosine, CPA; 0.033-330 pmol/50 nl). CPA evoked typical dose-dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA, and LSNA toward higher mean arterial pressure (MAP) in a dose-dependent manner; the maximal shifts were 52.6 +/- 2.8, 48.0 +/- 3.6, and 56.8 +/- 6.7 mmHg for pre-ASNA, RSNA, and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting because they were two to three times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upward: the maximal increases of upper and lower plateaus were 41.8 +/- 16.4% and 45.3 +/- 8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0 +/- 0.6 vs. 4.9 +/- 1.3), decreased for RSNA (4.1 +/- 0.6 vs. 2.3 +/- 0.3), and remained unaltered for LSNA (2.1 +/- 0.2 vs. 2.0 +/- 0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex control of regional sympathetic outputs.

Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

“…With the normalization procedure used, the range of SNA variation was smaller for LSNA than for RSNA, which accorded with the visual inspection of raw data. As a consequence, and although the slope coefficient P 2 did not differ between the two SNAs, the LSNA gain was markedly lower than the RSNA gain, which is in agreement with previous studies in anesthetized rats (29,30).…”

“…Both methods for assessing sympathetic baroreflex control revealed a significantly lower BRS for LSNA than for RSNA, which is in agreement with earlier observations in anesthetized rats (29,30). It is known that most, if not all, renal sympathetic nerve fibers are responsive to the stimulation of arterial baroreceptors (9,25).…”

“…In the meantime, evidence has accumulated suggesting a differential baroreflex control of regional SNAs in several animal species (22). In the rat, the comparison of the baroreflex control of regional SNAs has been carried out in urethane-chloralose anesthetized animals by using the vasoactive drug injection technique, i.e., the so-called pharmacological method (29,30). In these studies, it was reported that the characteristics of the baroreflex function curves differed between RSNA, lumbar SNA (LSNA), and adrenal SNA.…”

Neural and humoral control of regional vascular beds via A1 adenosine receptors located in the nucleus tractus solitarii

“…Therefore, adenosine is an important neuromodulator helping to regain homeostasis in these lifethreatening situations via specific modulation of central mechanisms of cardiovascular control. Although adenosine is released globally, it may, however, differentially modulate autonomic reflexes integrated in the NTS (20,34). The differential action of adenosine is most likely due to differential localization of adenosine receptor subtypes on NTS terminals/interneurons involved in different reflexes that finally target different sympathetic outputs and vascular beds as we suggested previously (35,40).…”

Natural Protection Against Cardiac Arrhythmias During Hibernation: Significance of Adenosine

“…Adenosine modulates the cardiovascular system through numerous A 1 AR in nucleus tractus solitarius (NTS) (Badman and Flier, 2005;Scislo et al, 2008) located in the brainstem which receives projections from hypothalamus, the thermoregulatory center in the brain (Scislo and O'Leary, 2006). Cardiovascular centers of the medulla are innervated by projections from the hypothalamus which alleviates cardiac arrhythmias by modulating the blood pressure (Willette et al, 1984;Lumb and Lovick, 1993;Kiely and Gordon, 1994;Hirasawa et al, 1996;Krukoff et al, 1997;Yang and Coote, 1998;Hardy, 2001).…”