Increased expression of angiotensin converting enzyme 2 in conjunction with reduction of neointima by angiotensin II type 1 receptor blockade.
Angiotensin converting enzyme 2 (ACE2), a newly recognized homolog of ACE that converts angiotensin II (Ang II) to angiotensin-1-7 (Ang-(1-7)), is found in vascular smooth muscle cells. Expression of ACE2 may be a local determinant of vascular Ang-(1-7) production and, when increased, may augment the increasingly recognized protective effects of this peptide within injured tissues. We previously showed that treatment with the angiotensin II type 1 (AT1) receptor blocker (ARB) olmesartan increased aortic ACE2 and Ang-(1-7) in conjunction with improved vascular remodeling in spontaneously hypertensive rats (SHR). In the present study, we investigated balloon injury-related ACE2 in the vasculature by determining the effect of sustained AT1 blockade on ACE2 protein expression in the carotid arteries of 12-week-old male SHR treated with either vehicle (n=5) or 10 mg/kg olmesartan (n=5) in drinking water for 14 days. Olmesartan treatment caused a 61% reduction in the cross-sectional area of the neointima, from 0.27+/-0.01 mm2 in vehicle-treated rats to 0.11+/-0.01 mm2 in olmesartan-treated rats. In contrast, olmesartan treatment had no effect on the medial area of injured or uninjured carotid arteries compared to that in vehicle-treated rats. Quantitative analysis of ACE2 immunostaining intensity in the carotid artery of SHR was significantly greater (p<0.05) in the neointima of olmesartan-treated SHR compared to that in vehicle-treated animals. In contrast, ACE2 immunostaining intensity was not quantitatively different in uninjured carotid arteries of olmesartan and vehicle-treated animals. These studies suggest that changes in ACE2 within the vascular system of SHR are regulated by a factor other than arterial pressure.
Igase
Michiya
M
Department of Geriatric Medicine, Ehime University School of Medicine, Toon, Japan. migase@m.ehime-u.ac.jp
Kohara
Katsuhiko
K
Nagai
Tokihisa
T
Miki
Tetsuro
T
Ferrario
Carlos M
CM
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; C437965:olmesartan; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)