title: Increased cardiac angiotensin II levels induce right and left ventricular hypertrophy in normotensive mice.
abstract: Angiotensin II is a potent arterial vasoconstrictor and induces hypertension. Angiotensin II also exerts a trophic effect on cardiomyocytes in vitro. The goals of the present study were to document an in vivo increase in cardiac angiotensins in the absence of elevated plasma levels or hypertension and to investigate prevention or regression of ventricular hypertrophy by renin-angiotensin system blockade. We demonstrate that high cardiac angiotensin II is directly responsible for right and left ventricular hypertrophy. We used transgenic mice overexpressing angiotensinogen in cardiomyocytes characterized by cardiac hypertrophy without fibrosis and normal blood pressure. Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent or normalize ventricular hypertrophy. Surprisingly, in control mice, receptor blockade decreases tissue angiotensin II despite increased plasma levels. This suggests that angiotensin II may be protected from metabolization by binding to its receptor. Blocking of the angiotensin II type 1 receptor rather than enhanced stimulation of the angiotensin II type 2 receptor may prevent remodeling and account for the beneficial effects of angiotensin antagonists.
authors.affiliation: Division of Hypertension and Vascular Medicine , University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Mazzolai
authors.forename: T
authors.initials: T
authors.lastname: Pedrazzini
authors.forename: F
authors.initials: F
authors.lastname: Nicoud
authors.forename: G
authors.initials: G
authors.lastname: Gabbiani
authors.forename: H R
authors.initials: HR
authors.lastname: Brunner
authors.forename: J
authors.initials: J
authors.lastname: Nussberger
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism; D017380:Hypertrophy, Right Ventricular / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism*
chemical_list: D000804:Angiotensin II