Neurotransmission of the Peripheral Chemoreflex in the Nucleus Tractus Solitarii in Unanesthetized Experimental Models

Peripheral chemoreflex activation with potassium cyanide (KCN) in awake rats, or in the working heart brainstem preparation (WHBP) produces: (a) a pressor response and sympathoexcitation; (b) bradycardia; and (c) tachypnea and an increase in the frequency of phrenic nerve activity (PNA). During the last few years in our laboratory, we have studied the neurotransmission of the sympathoexcitatory components of the chemoreflex within the nucleus tractus solitary (NTS) in unanesthetized experimental models. Re cently, we verified that simultaneous antagonism of ionotropic gluta-mate receptors and purinergic P2 receptors by sequential microinjections of kynurenic acid (a non selective antagonist of ionotropic glutamate receptors) and PPADS (a non-selective antagonist of P2 receptors) into the NTS elicited a significant reduction in the pressor and bradycardic responses but no changes in the tachypneic response to chemoreflex activation in awake rats. Microinjection of kynurenic acid and PPADS into the caudal commissural NTS of the WHBP almost abolished the increase in thoracic sympathetic activity and the bradycardic response but produced no change in the increase of the frequency of PNA. The data indicate that combined microinjections of PPADS and kynurenic acid into the NTS are required to block the sympathoexcitatory response to peripheral chemoreflex activation, suggesting an interaction of L-glutamate and ATP in this neurotransmission. In this review, I explain why we are using unanesthetized models in our experiments and also present the perspectives for a better understanding of the complex interaction of glutamatergic and purinergic mechanisms involved in the processing of the sympathoexcitatory component of the chemoreflex at the NTS level.