The Role Played by Adenosine in Modulating Reflex Sympathetic and Pressor Responses Evoked by Stimulation of TRPV1 in Muscle Afferents

BACKGROUND/AIMS: Activation of metabolite-sensitive transient receptor potential vanilloid type 1 (TRPV1) receptors (capsaicin receptors) in afferent nerves of the hindlimb muscles of rats increases renal sympathetic nerve activity (RSNA) and blood pressure (BP) via a reflex mechanism. The purpose of this study was to examine the role of adenosine in modulating the reflex RSNA and BP responses to stimulation of TRPV1. METHODS: RSNA and BP responses were recorded in rats. Immunofluorescence and patch-clamp methods were employed to examine the receptor mechanisms responsible for the effects of adenosine. RESULTS: Adenosine, in the concentration of 100 µM, injected into the femoral artery had an inhibitory effect on the reflex RSNA and BP responses induced by capsaicin. Likewise, arterial injection of adenosine analogue CGS21680 (A2A subtype receptor agonist, 10 µM and100 µM) also attenuated the reflex responses. In addition, co-existence of A2A and TRPV1 was observed in the dorsal root ganglion neurons. The prior application of adenosine or CGS21680 inhibited the magnitude of capsaicin-induced currents in muscle sensory neurons. CONCLUSION: Adenosine contributes to muscle afferent TRPV1-engaged reflex sympathetic and pressor responses. It is likely that TRPV1 response is impaired as the levels of adenosine are increased in the hindlimb muscles under diseased conditions.