Inhibition of glial glutamate transporter GLT1 in the nucleus tractus solitarii attenuates baroreflex control of sympathetic nerve activity and heart rate

Abstract

Astrocyte glutamate transporter (GLT‐1) removes neuronally released glutamate from the extracellular space. We examined the effect of inhibiting GLT1 in the nucleus tractus solitarii (NTS) on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) in Inactin anesthetized and artificially ventilated Sprague‐Dawley rats. In experiment 1, it was found that dihydrokainate (DHK; inhibitor of GLT1, 5mM, 100nl) injections into the NTS (n=4) decreased MAP (49±12mmHg), RSNA (84±15%) and HR (34±5bpm). Application of kynurenate (KYN; glutamate receptor antagonist, 5mM, 30μl) to the dorsal surface of the brainstem (n=4) blocked responses to NTS injections of DHK with MAP now only decreasing by 14±12mmHg, RSNA by 26±27% and HR by 10±8bpm (p<0.001). The DHK response returned after 30min. In experiment 2, the effect of DHK on arterial baroreflex was examined using i.v. infusions of phenylephrine and nitroprusside. NTS infusions of DHK (5mM, 40nl/min; n=6) reduced baroreflex response range (maximum ‐ minimum) of RSNA by 91±2% and HR by 83±5% (p<0.001). These results indicate that inhibition of GLT1 decreases MAP, RSNA and HR by indirect activation of ionotropic glutamate receptors and that the astrocytic glutamate transporter in the intermediate NTS plays an important role in the maintenance and regulation of cardiovascular function. Supported by HL‐088052