Sympathoexcitatory Response to Exogenous Angiotensin II in the Rostral Ventrolateral Medulla Depends on Local Iontotropic Glutamate Receptors

Abstract

Glutamate and angiotensin II (AngII) regulate the excitability of sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM). However, limited evidence is available regarding whether these two neurotransmitters interact within the RVLM to regulate sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Therefore, the present study examined whether blockade of either iontotropic glutamate or AngII‐type 1 receptors modulated the sympathoexcitatory response to exogenous AngII or glutamate, respectively. In urethane‐chloralose anesthetized rats, unilateral injection (60nL) of the AT1R antagonist losartan (1nmol, n=3) into the RVLM did not affect the increase in renal SNA (114±12 vs 97±14%) and mean ABP (27±2 vs 24±1 mmHg) to 1nmol glutamate. Losartan did eliminate the increase in renal SNA (50±6 vs 0±0%) and ABP (20±2 vs 0±0 mmHg) evoked by 60pmol AngII. In marked contrast, unilateral injection of the iontotropic glutamate receptor antagonist kynurenic acid (3nmol, n=6) into the RVLM eliminated the AngII‐evoked increase in renal SNA (50±6 vs 1±1%) and mean ABP (24±1 vs 0±1mmHg) but not the sympathoexictatory response to 1nmol carbachol (renal SNA: 45±2%; mean ABP: 32±2mmHg, n=3). These findings suggest that iontotropic glutamate receptors mediate the sympathoexcitatory response to exogenously applied AngII in the RVLM. Supported by NIH HL090826, AHA 0630202N, AHA0815372D