title: Angiotensin-converting enzyme 2 over-expression in the central nervous system reduces angiotensin-II-mediated cardiac hypertrophy.
abstract: Angiotensin-converting enzyme type 2 (ACE2) has been shown to be an important member of the renin angiotensin system. Previously, we observed that central ACE2 reduces the development of hypertension following chronic angiotensin II (Ang-II) infusion in syn-hACE2 transgenic (SA) mice, in which the human ACE2 transgene is selectively targeted to neurons. To study the physiological consequences of central ACE2 over-expression on cardiac function and cardiac hypertrophy, SA and non-transgenic (NT) mice were infused with Ang-II (600 ng/kg/min, sc) for 14 days, and cardiac function was assessed by echocardiography. Blood pressure (BP), hemodynamic parameters, left ventricle (LV) mass/tibia length, relative ventricle wall thickness (2PW/LVD), cardiomyocyte diameters and collagen deposition were similar (P>0.05) between NT and SA mice during saline infusion. After a 2-week infusion, BP was elevated in NT but not in SA mice. Although ejection fraction and fractional shortening were not altered, Ang-II infusion increased 2PW/LVD compared to saline infusion in NT mice. Interestingly, the 2PW/LVD and LV mass/tibia ratios were significantly lower in SA compared to NT mice at the end of infusion. Moreover, Ang-II infusion significantly increased arterial collagen deposition and cardiomyocytes diameter in NT mice but not in transgenic animals (P<0.05). More importantly, ACE2 over expression significantly reduced the Ang-II-mediated increase in urine norepinephrine levels in SA compared to NT mice. The protective effect of ACE2 appears to involve reductions in Ang-II-mediated hypertension and sympathetic nerve activity.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics and Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Feng
authors.forename: Chetan
authors.initials: C
authors.lastname: Hans
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McIlwain
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Varner
authors.forename: Eric
authors.initials: E
authors.lastname: Lazartigues
mesh_terms: D000804:Angiotensin II; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D009638:Norepinephrine