Neurociencia

Autonomic Neuroscience: Basic and Clinical 160 (2011) 90–98

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Autonomic Neuroscience: Basic and Clinical
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / a u t n e u

Cardiovascular effects of noradrenaline microinjected into the insular cortex of unanesthetized rats
Fernando H.F. Alves a, Carlos C. Crestani b, LeonardoB.M. Resstel a, Fernando M.A. Correa a,⁎
a b

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, UNESP, Araraquara, SP, 14801-902, Brazil

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a b s t r a c t
The insularcortex (IC) has been reported to be involved in central cardiovascular control. In the present study, we investigated the cardiovascular responses evoked by microinjection of noradrenaline into the IC as well as the central and peripheral mechanisms involved in their mediation. Microinjection of noradrenaline into the IC (3, 7, 10, 15, 30 and 45 nmol/100 nL) caused long-lasting dose-related pressorand bradycardiac responses. The cardiovascular responses evoked by 15 nmol of noradrenaline were blocked by IC pretreatment with WB4101 or 5-methyl-urapidil, selective α1-adrenoceptor antagonists. IC pretreatment with either the selective α2-adrenoceptor antagonists RX821002 or the β-adrenoceptor antagonist propranolol did not affect noradrenaline cardiovascular responses. Noradrenalinecardiovascular responses were mimicked by microinjection of the selective α1-adrenoceptor agonist phenylephrine into the IC, thus reinforcing the idea that α1-adrenoceptors mediate cardiovascular responses to noradrenaline microinjected into the IC. The pressor response to noradrenaline microinjection was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and inhibited by i.v.pretreatment with the selective V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP. The bradycardiac response to noradrenaline microinjection into the IC was abolished by pretreatment with either pentolinium or the V1-vasopressin receptor antagonist, indicating its reflex origin. In conclusion, our results suggest that pressor response evoked by microinjection of noradrenaline into the IC involve theactivation of IC α1-adrenoceptors to cause the release of vasopressin into the circulation. © 2010 Elsevier B.V. All rights reserved.

Article history: Received 11 August 2010 Received in revised form 28 October 2010 Accepted 2 November 2010 Keywords: Prefrontal cortex Blood pressure Heart rate Noradrenergic neurotransmission Adrenoceptors Vasopressin

1. Introduction It was assumed before the1960s that rats did not have a cortical structure analogous to the prefrontal cortex of primates (Rose and Woolsey, 1948). However, Leonard (1969) described projections from the dorsal medial thalamic nucleus to two distinct frontal cortex regions of the rat brain that could be defined as prefrontal cortex. The prefrontal cortex is a limbic region, which integrates sensory and visceral informationfrom peripheral receptors and has been implicated in control of autonomic activity (Anand and Dua, 1956; Delgado, 1960; Neafsey, 1990; Resstel and Correa, 2006). In rats, the prefrontal cortex has been anatomically divided into two main regions: the lateral prefrontal cortex or insular cortex (IC) and the medial prefrontal cortex (mPFC) (Krettek and Price, 1977; Leonard, 1969). The IC has beenproposed to be involved in cardiovascular regulation (Allen and Cechetto, 1995; Alves et al., 2009a, 2010; Ruggiero et al., 1987). Its electrical or chemical stimulation has been reported to cause either pressor or depressor responses (Allen and Cechetto,
⁎ Corresponding author. Department of Pharmacology, School of Medicine of Ribeirão Preto, USP, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto,...