Abstract
The rostral ventrolateral medulla (RVLM) plays a critical role in control of cardiovascular regulation. The increased tonic glutamatergic input to the RVLM contributes to high blood pressure and enhanced sympathetic outflow in hypertensive rats. Recently, it has been reported that overexpression of angiotensin-converting enzyme 2 (ACE2) is capable of lowering high blood pressure in the spontaneously hypertensive rat (SHR). Thus, the aim of this study was to determine the effect of ACE2 gene transfer on tonically acting glutamatergic input to the RVLM in the SHR. It was confirmed that protein expression of ACE2 in the RVLM was increased by an average of 66% in the SHR treated with lentiviral-mediated overexpression of ACE2 (lenti-ACE2) compared with lenti-green fluorescent protein (GFP). A significant reduction in resting blood pressure and the 24-h urinary excretion of norepinephrine was observed in the SHR treated with lenti-ACE2 in the RVLM compared with lenti-GFP. Overexpression of ACE2 significantly reduced the concentration of glutamate (1586±142 μg/L in lenti-GFP versus 621±60 μg/L in lenti-ACE2) from microdialysis-liquid from the RVLM of the SHR. Furthermore, a decrease in resting blood pressure, heart rate, and renal sympathetic nerve activity evoked by microinjection of the glutamate receptor antagonist kynurenic acid (2.7 nmol) into the RVLM was significantly blunted in the SHR treated with lenti-ACE2 compared with lenti-GFP. Based on these data, we suggest that the beneficial effect of ACE2 overexpression in the RVLM on hypertension is associated with reduction in the tonically acting glutamatergic input to the RVLM. (Supported by NSCF: 81170240)
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