Effects of activation and blockade of P2x receptors in the ventrolateral medulla on arterial pressure and sympathetic activity

Sympathoexcitatory and sympathoinhibitory neurons in the rostral and caudal ventrolateral medulla (VLM) play a crucial role in the tonic and reflex control of sympathetic vasomotor activity. Recent evidence also indicates that the VLM contains a high density of P-2x purinoceptors. In this study, we investigated the cardiovascular effects of selective activation of P-2x purinoceptors in the rostral and caudal VLM, and the effects of blockade of P-2x purinoceptors in the rostral VLM on the tonic and reflex control of sympathetic vasomotor activity. In anesthetized barodenervated rabbits, microinjection into the rostral and caudal VLM of the P-2x purinoceptor agonist, alpha,beta-methylene adenosine triphosphate (alpha,beta-meATP) (4-400 pmol) elicited dose-dependent increases and decreases, respectively, in arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA). The response evoked by alpha,beta-meATP in the rostral VLM was blocked by prior injection into the same site of the P-2 purinoceptor antagonist suramin but not by the ionotropic glutamate receptor antagonist kynurenic acid. Bilateral injections of suramin into the rostral VLM sympathoexcitatory region had no significant effect on resting cardiovascular variables, nor on the reflex increase in RSNA evoked by sciatic nerve stimulation (which is known to be mediated by the rostral VLM sympathoexcitatory neurons). The results demonstrate that: (1) activation of P-2x purinoceptors in the VLM are capable of producing marked excitation of both sympathoexcitatory and sympathoinhibitory neurons; (2) these effects are not due to modulation of glutamatergic inputs to these neurons; and (3) P-2x purinoceptors do not play a significant role in maintaining the tonic activity of rostral VLM sympathoexcitatory neurons or in modulating their responses to excitatory synaptic inputs evoked by stimulation of sciatic nerve afferents. (C) 1999 Elsevier Science B.V. AU rights reserved.