Purinergic modulation of cardiovascular function in the rat locus coeruleus

Abstract

1 The purpose of the present study was to determine whether purines exerted a physiological role in central cardiovascular modulation at the level of the locus coeruleus (LC). 2 In pentobarbitone-anaesthetised Wistar-Kyoto rats, unilateral microinjection of ATP or alpha,beta-methyleneATP into the LC elicited dose-related decreases in blood pressure and heart rate. Unilateral microinjection of the P2 purinoceptor antagonists suramin and PPADS, caused pressor and tachycardic responses. Administration of the selective P2X(1) receptor antagonist NF-279 had no effect. While both ATP and L-glutamate (L-GLU) resulted in depressor responses after intra-LC microinjection, following intra-LC microinjection of P2 purinoceptor antagonists into the LC, the effects of subsequent administration of either ATP or L-GLU were functionally reversed, such that a pressor response ensued. 3 Microinjection of noradrenaline into the LC caused an increase in blood pressure and heart rate; however, the alpha(2)-adrenoceptor antagonist idazoxan had no cardiovascular effects, but did prevent the pressor response to PPADS or suramin. In addition, coinjection of idazoxan with either suramin or PPADS abolished the ATP and L-GLU mediated pressor responses observed following either suramin or PPADS administration. 4 The present data suggest that firstly, purines are capable of acting within the LC to ultimately modulate the cardiovascular system and secondly, that there is apparently a functional interaction between tonically active purinergic and noradrenergic systems within the LC of the rat.