Research report The hypothalamic paraventricular nucleus and carotid receptors modulate hyperglycemia induced by hemorrhage Simonton Andrade Silveira, Nilo Resende Viana Lima, Andre ´a Siqueira Haibara, Ca ˆndido Celso Coimbra * Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, ICB-UFMG, 6627 Av. Antonio Carlos, 31270-901 Belo Horizonte, MG, Brazil Accepted 10 September 2003 Abstract The aim of this study was to assess the role of cholinergic transmission in the paraventricular nucleus of the hypothalamus (PVN) and carotid body receptors in mediating a rise in plasma glucose levels in response to hemorrhagic hypotension in rats. Methylatropine (1 Â 10 À 9 mol) or 0.15 M NaCl (0.2 Al) was injected into the PVN of Wistar rats weighing 250– 300 g bearing a chronic jugular catheter for blood sampling and hemorrhage (1.2 ml/100 g/2 min). Polyethylene cannulae (PE-10) were inserted into the left femoral artery for cardiovascular monitoring. In the other experimental protocol, hemorrhage was performed on rats submitted to bilateral carotid receptor denervation (H-CD). The results show that the hyperglycemic response to hemorrhage was decreased by either methylatropine (H- MA) treatment or bilateral carotid receptor denervation (10.3 F 0.4 mM, control, n = 15 vs. 7.7 F 0.2 mM, H-MA, n = 12, and 7.6 F 0.3 mM, H-CD, n = 5, p < 0.01). Furthermore, methylatropine did not affect the recovery of blood pressure after hemorrhage-induced hypotension, suggesting that the metabolic and pressor adjustments have different efferent pathways. Our data demonstrate that cholinergic input from the PVN and carotid receptors (chemo- and/or baroreceptors) might participate in the same neural pathway activated by hemorrhage-induced hypotension that produces hyperglycemia. D 2003 Elsevier B.V. All rights reserved. Theme: Endocrine and autonomic regulation Topic: Neuroendocrine regulation: other Keywords: PVN; Methylatropine; Hemorrhage; Plasma glucose; Carotid receptor 1. Introduction Hemorrhage is a powerful stimulus that induces glucose and lactate elevation in plasma, as do many other stressful conditions [19,39]. This response is the result of integration of the stress signal in the hypothalamus and in particularly in the paraventricular nucleus of hypothalamus (PVN) [2,25]. It is well known that hemorrhagic hypotension decreases baroreceptor discharge and leads to chemorecep- tor stimulation, due to stagnant anoxia induced by decreased blood flow to the chemoreceptors [7]. These afferents information are relayed from carotid receptors (chemo- and baroreceptors) to the nucleus of the solitary tract (NTS) [26]. Among other destinations, neurons of NTS project to the A1 region of the caudal ventrolateral medulla (CVLM), to the PVN and to the rostral ventrolateral medulla (RVLM) [26]. The CVLM then also projects to the RVLM, the region containing neurons that excite sympathetic pre- ganglionic neurons in the spinal cord [2,7,26,33]. On the other hand, PVN contains neurons that also send projections to autonomic regions important in cardiovascular regulation, such as the NTS, RVLM and the intermediolateral cell column of the thoracolumbar spinal cord, the site of sym- pathetic preganglionic motoneurons [3,26]. Those connec- tions to the RVLM and to sympathetic preganglionic neurons in the spinal cord would provide the PVN with a mechanism which could potentially influence cardiovascu- lar and metabolic adjustments induced by reflex sympathetic changes. Although it has been demonstrated that there are 0006-8993/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.09.013 * Corresponding author. Tel.: +55-31-3499-2936; fax: +55-31-3499- 2924. E-mail address: coimbrac@icb.ufmg.br (C.C. Coimbra). www.elsevier.com/locate/brainres Brain Research 993 (2003) 183 – 191