Increased Group I Metabotropic Glutamate Receptor Activity in Paraventricular Nucleus Contributes to Elevated Sympathetic Vasomotor Tone in Hypertension

Abstract

Enhanced glutamatergic input in the paraventricular nucleus (PVN) contributes to elevated sympathetic outflow in hypertension. We determined the role of group I metabotropic glutamate receptors (mGluRs) in the PVN in the control of sympathetic outflow in spontaneously hypertensive rats (SHR). Lumbar sympathetic nerve activity (LSNA), arterial blood pressure (Bp), and heart rate (HR) were recorded from anesthetized SHR and WKY rats. Bilateral microinjection of MPEP (1–10 nmol), a mGluR5 antagonist, or LY367385 (10–100 nmol), a mGluR1 antagonist, into the PVN dose‐dependently decreased LSNA and Bp in SHR but not in WKY. MPEP‐induced decreases in LSNA and Bp were greater than that produced by LY367385 in SHR. Furthermore, microinjection of group I mGluR agonist DHPG (10–100 nmol) caused dose‐dependent increase in LSNA and Bp in both WKY and SHR. DHPG‐induced responses were significantly attenuated by MPEP or LY367385 and abolished by a combination of MPEP and LY367385 in both WKY and SHR. In addition, prior injection of NMDA receptor antagonist AP5 (1.4 nmol) into the PVN decreased LSNA and Bp in SHR and attenuated DHPG‐induced sympathoexcitation in both WKY and SHR. Thus, our study suggests that elevated sympathetic outflow is maintained by activation of group I mGluR receptors in the PVN in SHR. Increased group I mGluR receptor activity contributes to increased glutamatergic input via NMDA receptor in hypertension.