Cardiovascular effects of L-glutamate microinjection in the supraoptic nucleus of unanaesthetized rats C. Busnardo a , R.F. Tavares a , J. Antunes-Rodrigues b , F.M.A. Corre ˆa a, * a Department of Pharmacology, School of Medicine of Ribeir~ ao Preto, University of S~ ao Paulo, Av. Bandeirantes 3900, 14049 900 Ribeir~ ao Preto, SP, Brazil b Department of Physiology, School of Medicine of Ribeir~ ao Preto, University of S~ ao Paulo, Av. Bandeirantes 3900, 14049 900 Ribeir~ ao Preto, SP, Brazil Received 1 August 2006; received in revised form 22 January 2007; accepted 23 January 2007 Abstract We report on the cardiovascular effects of L-glutamate (L-glu) microinjection in the hypothalamic supraoptic nucleus (SON) as well as possible receptor and mechanisms involved. Microinjection of L-glu in 100 nL in the SON caused dose-related pressor and bradycardic responses in unanesthetized rats. Responses were markedly reduced in urethane-anesthetized rats. The response to L-glu 10 nmol was blocked by local pretreatment with 2 nmol of the non-NMDA-receptors antagonist NBQX and not affected by 2 nmol of the selective NMDA-receptor antagonist LY 235959, suggesting that non-NMDA receptors mediate these responses. The pressor and bradycardic response to L-glu was potentiated by intravenous pretreatment with the ganglion blocker pentolinium and was blocked by intravenous pretreatment with the V 1 -vasopressin receptor antagonist dTyr(CH 2 ) 5 (Me)AVP, suggesting involvement of circulating vasopressin in this response. Additionally L-glu microinjection into the SON increased plasma vasopressin levels (control: 1.3  0.2 pg/mL, n ¼ 6; L-glu: 14.7  2.3 pg/mL, n ¼ 6). In conclusion the results suggest that pressor responses to SON microinjection of L-glu are caused by activation of non-NMDA glutamate receptors and mediated by vasopressin release into systemic circulation. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Blood pressure; Heart rate; Supraoptic nucleus; L-glutamate; Glutamatergic receptors; Vasopressin 1. Introduction The hypothalamic supraoptic nucleus (SON) contains cells magnocellular that release vasopressin and oxytocin, which regulates water balance, cardiovascular function, parturition and lactation. Electrophysiological studies showed that vaso- pressinergic but not oxytocinergic neurons are inhibited by baroreceptor stimulation, suggesting their involvement in car- diovascular modulation (Cunningham et al., 2002). Ciriello and Calaresu (1980) reported increased blood pres- sure and heart rate after electrical stimulation of the paraven- tricular nucleus (PVN) or the SON in cats. The observed heart rate increase was abolished in vagotomized and sympathecto- mized cats whereas the pressor response was only partially reduced leading to the suggestion that the remaining response could be related to vasopressin release (Ciriello and Calaresu, 1980). Glutamate is an abundant excitatory amino acid in the cen- tral nervous system (CNS) and magnocellular hypothalamic neurons receive dense glutamatergic innervation (Boudaba et al., 2003). SON magnocellular neurons were reported to be involved in osmotically induced vasopressin release (Sladek et al., 1995). These authors reported inhibition of hy- perosmotic stimulation-induced vasopressin release in hypo- thalamic explants after administration of kynurenic acid. Although there is strong evidence of vasopressin-mediated pressor responses after SON stimulation, there is none on the effects of excitatory amino acid administration in the * Corresponding author. Tel.: þ55 16 602 3206; fax: þ55 16 3633 2301. E-mail address: fmdacorr@fmrp.usp.br (F.M.A. Corre ˆa). 0028-3908/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropharm.2007.01.011 Neuropharmacology 52 (2007) 1378e1384 www.elsevier.com/locate/neuropharm