Mechanisms mediating regional sympathoactivatory responses to stimulation of NTS A₁ adenosine receptors

Abstract

Selective activation of adenosine A(1) and A(2a) receptors in the subpostremal nucleus tractus solitarius (NTS) increases and decreases mean arterial pressure (MAP), respectively, and decreases heart rate (HR). We have previously shown that the decreases in MAP evoked by NTS A(2a) receptor stimulation were accompanied with differential sympathetic responses in renal (RSNA), lumbar (LSNA), and preganglionic adrenal sympathetic nerve activity (pre-ASNA). Therefore, now we investigated whether stimulation of NTS A(1) receptors via unilateral microinjection of N(6)-cyclopentyladenosine (CPA) elicits differential activation of the same sympathetic outputs in alpha-chloralose-urethane-anesthetized male Sprague-Dawley rats. CPA (0.33-330.0 pmol in 50 nl) evoked dose-dependent increases in MAP, variable decreases in HR, and differential increases in all recorded sympathetic outputs: upward arrow pre-ASNA >> upward arrow RSNA > or = upward arrow LSNA. Sinoaortic denervation + vagotomy abolished the MAP and LSNA responses, reversed the normal increases in RSNA into decreases, and significantly attenuated increases in pre-ASNA. NTS ionotropic glutamatergic receptor blockade with kynurenate sodium (4.4 nmol/100 nl) reversed the responses in MAP, LSNA, and RSNA and attenuated the responses in pre-ASNA. We conclude that afferent inputs and intact glutamatergic transmission in the NTS are necessary to mediate the pressor and differential sympathoactivatory responses to stimulation of NTS A(1) receptors.

Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically

“…However, this study also shows POMC neurons to be synaptically linked to eWAT and liver. Our studies also show dual-labeled neurons in the NTS, a region known to modulate multiple sympathetic responses (33)(34)(35). We found NTS NPY but not POMC neurons innervate both liver and eWAT, and thus, they may be part of the common outflow to liver and eWAT.…”

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

“…A possible explanation is that the increase in AP was presumably due to vasoconstriction in mesenteric arteries [4,13] but also partly in consequence of a rise in cardiac output (tachycardia). The increase in AP baseline following suramin or kynurenate microinjected into the NTS was similar to reports in previous studies [35][36][37][38]. Although the cardiovascular changes reverted to resting values prior to injections after ∼20-30 min, the receptors remained blocked by the antagonists that were tested by respective agonists.…”

Sistemas neuromodulatórios: implicações fisiopatológicas

“…Estes resultados estão de acordo com os apresentados por Phillis e colaboradores (1997) os quais sugeriram uma distribuição heterogênea dos receptores de adenosina dentro do NTS. Estudos anteriores de nosso laboratório também demonstraram a existência de populações separadas de receptores A1 de adenosina dentro do NTS de ratos adultos (Carrettiero & Fior-Chadi, 2004), as quais seriam responsáveis por mediar respostas cardiovasculares diferenciadas (Scislo & O'Leary, 2002).…”

“…Numerosos estudos têm mostrado que a adenosina modula o controle cardiovascular no núcleo do trato solitario (NTS) Barraco et al, 1996;Mosqueda-Garcia et al, 1991;Mosqueda-Garcia et al, 1989;Scislo et al, 2001;Scislo & O'Leary, 1998;Scislo & O'Leary, 2000;Scislo & O'Leary, 2002;St Lambert et al, 1997;Tao & Abdel-Rahman, 1993). No entanto, o exato mecanismo deste processo ainda não é bem entendido.…”

“…Numerosos trabalhos têm demonstrado que a adenosina modula o controle cardiovascular dentro deste núcleo em ratos adultos (Barraco et al, 1996;Mosqueda-Garcia et al, 1989;Scislo et al, 2001;Scislo & O'Leary, 1998;Scislo & O'Leary, 2000;Scislo & O'Leary, 2002;St Lambert et al, 1997;Tao & Abdel-Rahman, 1993). Sabe-se também, que os receptores de adenosina estão alterados no NTS de ratos espontaneamente hipertensos (SHR) (Green, 1991;Illes et al, 1989;Matias et al, 1991;Matias et al, 1993;Robertson et al, 1988), sugerindo um papel importante deste nucleosídeo sobre a rede neural responsável pelo controle da pressão arterial.…”