Role of the Locus coeruleus purinergic system in cardiorespiratory control under normocapnic and hypercapnic conditions in unanesthetized male rats

Abstract

Locus coeruleus (LC) purinergic neuromodulation is of particular interest because adenosine 5′‐triphosphate (ATP) acts as a neuromodulator in brainstem regions involved in cardiovascular and respiratory regulation such as the LC. Thus, the goal of the present study was to investigate the role of LC purinergic neuromodulation in cardiorespiratory responses during normocapnia and hypercapnia in unanesthetized Wistar male rats. We microinjected an ATP P2X receptor agonist (a,ß‐MeATP, 0.5 nmoL/40 nL and 1 nmoL/40 nL) and non‐selective P2 receptor antagonists (PPADS 0.5 nmoL/40 nL and 1 nmoL/40 nL; suramin, 1 nmoL/40 nL) into the LC. Pulmonary ventilation (VE, plethysmography), mean arterial pressure (MAP) and heart rate (HR) were determined before and after unilateral microinjection (40 nL) of a,ß‐MeATP, PPADS, suramin or 0.9% saline (vehicle) into the LC. Under normocapnic conditions, PPADS decreased respiratory frequency (f) and increased MAP and HR. Suramin increased MAP and HR. Hypercapnic conditions induced an increase in ventilation and a decrease in HR in all groups. Under hypercapnic conditions, α,β‐MeATP increased ventilation. PPADS increased MAP. Suramin increased both ventilation and MAP. Thus, our data suggest that purinergic signaling in the LC plays an important role in cardiorespiratory control under normocapnic and hypercapnic conditions in unanesthetized rats.