Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats

Wang, Yang-Kai, et al. "Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats." American Journal of Physiology-Heart and Circulatory Physiology (2014). This article was focused on the role of ACE2 in the RVLM and its effects on hypertension. Overexpression of ACE2 was achieved using microinjections of lentivirus, containing a GFP tag expressed upon transcription, into the RVLM. WKY, SHR, SHR-leniGFP, and SHR-lentiACE2 were observed for 6 weeks and measured for BP, HR, Norepinephrine excretion, and glutamate concentrations within the RVLM. Acute microinjection studies were also done with Kyn to look at responses to glutamatergic inhibition in the RVLM. It was found that three weeks following injections, BP and levels of NE excreation were significantly decreased from baseline in lentivirus-ACE2 positive animals but not in lenti-shams, SHR, or WKYs. It was also observed after acute microinjecitons of Kyn into the RVLM that SHR-ACE2 animals had decreased RSNA activity, and an attenuated decrease in blood pressure compared to the SHR-GFP animals. Lastly, it was discovered that with an upregulation of ACE2/Ang(1-7) there was a corresponding downregulation of the AT1R, NMDA receptor 1 protein, and GluR5/6/7 proteins. Contrarily, there was an upregulation of Mas receptor that Ang(1-7) is known to innervate. Based on this evidence the authors concluded that ACE2 attenuates tonically active glutamatergic inputs to the RVLm in SHR. They discussed possible mechanisms being through the upregulation of Mas interfering with glutamatergic neurotranmission at the level of the pre-synaptic cleft. However, further research is needed in order to characterize the exact mechanism in which ACE2 is attenuating glutamatergic input. Conclusively, this study provides evidence for the possible use of ACE2 as a therapeutic agent for hypertension. ~JI