Cardiovascular effects of L-glutamate injected in the medial prefrontal cortex of spontaneously hypertensive rats Leonardo B.M. Resstel ⁎ , Fernando M.A. Corrêa Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil Received 23 April 2007; received in revised form 16 October 2007; accepted 15 November 2007 Available online 23 November 2007 Abstract We have previously reported that L-glutamate (L-glu) injected into the ventral portion of medial prefrontal cortex (vMPFC) of unanesthetized normotensive Wistar rats elicited cardiovascular responses. In the present study we investigated whether the spontaneously hypertensive rat (SHR) exhibit abnormal cardiovascular responses after L-glu microinjection in the vMPFC. Microinjections of L-glu (3, 9, 27, 81 or 150 nmol/200 nl) caused long-lasting dose-related depressor and bradycardiac responses in unanesthetized SHR (n = 6, each dose). Pressor and tachycardiac responses were evoked after the injection of 81 nmol of L-glu in the vMPFC of normotensive Wistar rats (n = 6). Systemic pretreatment with the beta1- adrenoceptor antagonist atenolol (1.5 mg/kg, i.v.) had no effect on L-glu cardiovascular responses evoked in the SHR (n = 5). However, the treatment with the muscarinic antagonist homatropine methyl bromide (1 mg/kg, i.v.) blocked the bradycardiac response to L-glu, without significant effects on depressor response evoked by L-glu in the SHR (n = 5). These results indicate that the bradycardiac response to the injection of L-glu injection in the vMPFC is due to activation of the parasympathetic system and not to inhibition of the cardiac sympathetic input. In conclusion, results indicate opposite cardiovascular responses when L-glu was microinjected in the vMPFC of unanesthetized SHR or normotensive. The bradycardiac response observed in the SHR was due to parasympathetic activation and was not affected by pharmacological blockade of the cardiac sympathetic output. © 2007 Elsevier B.V. All rights reserved. Keywords: Medial prefrontal cortex; L-glutamate; Spontaneously hypertensive rat (SHR); Cardiovascular system; Autonomic nervous system 1. Introduction There are evidences that the ventral portion of medial pre- frontal cortex (vMPFC) plays a role in the central control of the blood pressure and heart rate, modulation both sympathetic and parasympathetic nervous activities (Owens et al., 1999; Crippa et al., 2000; Resstel et al., 2004; Resstel and Correa, 2005). Stimulation of the vMPFC has been reported to evoke either excitatory or inhibitory sympathetic-related cardiovascular responses, respectively in unanesthetized or anesthetized rats (Verberne, 1996; Resstel and Correa, 2006a). Additionally, the vMPFC has been shown to modulate baroreflex activity in normotensive Wistar rats (Verberne et al., 1987; Resstel et al., 2004; Resstel et al., 2005) as well as to be an important area for cardiovascular integration during stress response (Buijs and Van Eden, 2000). The spontaneously hypertensive rat (SHR) is a known animal model of hypertension that involves both neural and vascular abnormalities (Hallback and Folkow, 1974; Verberne et al., 1988). Differences between normotensive Wistar rats and the SHR in cardiovascular responses evoked during the defense reaction have been reported in the literature (Hallback and Folkow, 1974; Galeno et al., 1984). However, chronic or acute reversible ablation of the vMPFC had no influence on SHR baroreflex activity (Verberne et al., 1988; Resstel and Correa, 2006a), indicating that the vMPFC could play a different role in central cardiovascular modulation in the SHR. Several neurotransmitters present in the vMPFC were shown to contribute for cardiovascular regulation, such as acetylcho- line, noradrenaline and dopamine (Hardy and Mack, 1990; Funk and Stewart, 1996; Crippa et al., 1999; Fernandes et al., Available online at www.sciencedirect.com European Journal of Pharmacology 580 (2008) 372 – 379 www.elsevier.com/locate/ejphar ⁎ Corresponding author. Fax: +55 16 633 2301. E-mail address: leoresstel@yahoo.com.br (L.B.M. Resstel). 0014-2999/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2007.11.020