Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats.
The rostral ventrolateral medulla (RVLM) plays a key role in cardiovascular regulation. It has been reported that tonically active glutamatergic input to the RVLM is increased in hypertensive rats, whereas 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 (SHRs). 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 SHRs after overexpression of ACE2. A significant reduction in blood pressure and heart rate in SHRs was observed 6 wk 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 SHRs with lenti-ACE2 compared with lenti-GFP. ACE2 overexpression significantly attenuated 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 SHRs. Therefore, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced tonically active glutamatergic input in SHRs, which may be an important mechanism underlying the beneficial effect of central ACE2 to hypertension.
Department of Physiology, Second Military Medical University, Shanghai, China;
Yang-Kai
YK
Wang
Department of Physiology, Second Military Medical University, Shanghai, China;
Du
D
Shen
Department of Medical Imaging, Changhai Hospital, Shanghai, China;
Qiang
Q
Hao
Department of Neurobiology and Physiology, Ningxia Medical University, Yinchuan, China; and.
Qiang
Q
Yu
Department of Physiology, Second Military Medical University, Shanghai, China;
Zhao-Tang
ZT
Wu
Department of Neurobiology and Physiology, Ningxia Medical University, Yinchuan, China; and.
Yu
Y
Deng
Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, Ohio.
Yan-Fang
YF
Chen
Department of Neurobiology and Physiology, Ningxia Medical University, Yinchuan, China; and.
Wen-Jun
WJ
Yuan
Department of Neurobiology and Physiology, Ningxia Medical University, Yinchuan, China; and.
Qi-Kuan
QK
Hu
Department of Physiology, Second Military Medical University, Shanghai, China;
Ding-Feng
DF
Su
Department of Physiology, Second Military Medical University, Shanghai, China; wangwz68@hotmail.com.
Wei-Zhong
WZ
Wang
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D007267:Injections; D007736:Kynurenic Acid / Q000008:administration & dosage; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D009638:Norepinephrine / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D007736:Kynurenic Acid; D009638:Norepinephrine
gene transfer; glutamate; hypertension; renin-angiotensin system; sympathetic activity