Published online before print September 22, 2008, doi: 10.1161/HYPERTENSIONAHA.108.114322
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2008;52:967.)
© 2008 American Heart Association, Inc.
Original Articles |
Transgenic Angiotensin-Converting Enzyme 2 Overexpression in Vessels of SHRSP Rats Reduces Blood Pressure and Improves Endothelial Function
From the Max-Delbrück-Center for Molecular Medicine (B.R., M.T., R.I., E.P., L.A.C., O.C.B., M.B.), Berlin-Buch, Germany; the Department of Biology, Chemistry, and Pharmacy (B.R.), Free University Berlin, Germany; and the Department of Physiology and Biophysics (M.L.O., R.A.S.), Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Correspondence to Michael Bader, Prof PhD, Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, Berlin-Buch, D-13125, Germany. E-mail mbader{at}mdc-berlin.de
Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression compared with control animals. The aim of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in these models. Therefore, we generated transgenic rats on a SHRSP genetic background expressing the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter, called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity assays. Transgene expression leads to significantly increased circulating levels of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive response to intraarterial administration of angiotensin II was attenuated. The latter effect was abolished by previous administration of an ACE2 inhibitor. To evaluate the endothelial function in vivo, endothelium-dependent and endothelium-independent agents such as acetylcholine and sodium nitroprusside, respectively, were applied to the descending thoracic aorta and blood pressure was monitored. Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7) axis may be a novel therapeutic strategy in hypertension.
Key Words: ACE2 • angiotensin-(1-7) • angiotensin II • SHRSP • endothelial function
Related Article:
Hypertension 2008 52: 816-817.
This article has been cited by other articles:
 |
|
 |
|
  A. J. Turner Angiotensin-Converting Enzyme 2: Cardioprotective Player in the Renin-Angiotensin System? Hypertension, November 1, 2008; 52(5): 816 - 817. [Full Text] [PDF]
|
|