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

著者 Wang YK , Shen D , Hao Q , Yu Q , Wu ZT , Deng Y , Chen YF , Yuan WJ , Hu QK , Su DF , Wang WZ この記事をPubMed上で見るPubMedで表示
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The rostral ventrolateral medulla (RVLM) plays a key role in cardiovascular regulation, it is reported that tonically active glutamatergic input to the RVLM is increased in hypertensive rats while angiotensin-converting enzyme 2 (ACE2) in the brain has been suggested to be beneficial to hypertension. This study was designed to determine the effect of ACE2 gene transfer into the RVLM on tonically active glutamatergic input in spontaneously hypertensive rats (SHR). The lentiviral particles containing enhanced green fluorescent protein (lenti-GFP) or ACE2 (lenti-ACE2) were injected bilaterally into the RVLM. Both protein expression and activity of ACE2 in the RVLM were increased in the SHR after overexpression of ACE2. A significant reduction in blood pressure and heart rate in the SHR was observed 6 weeks after lenti-ACE2 injected into the RVLM. The concentration of glutamate in microdialysis fluid from the RVLM was significantly reduced by an average of 61% in the SHR with lenti-ACE2 compared with lenti-GFP. ACE2 overexpression significantly attenuates the decrease in blood pressure and renal sympathetic nerve activity evoked by bilateral injection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nl) into the RVLM in the SHR. Therefore, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced tonically active glutamatergic input in the SHR, which may be an important mechanism underlying the beneficial effect of central ACE2 to hypertension.
PMID: 24838502 [PubMed - as supplied by publisher]
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