(Circulation. 2001;104:346.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Angiotensin II Type 2 Receptor Is Essential for Left Ventricular Hypertrophy and Cardiac Fibrosis in Chronic Angiotensin II–Induced Hypertension
From the Department of Biochemistry and the Department of Medicine (F.A.G.), Vanderbilt University School of Medicine, Nashville, Tenn.
Correspondence to Tadashi Inagami, PhD, Department of Biochemistry, Vanderbilt University School of Medicine, 663 Light Hall, 23rd at Pierce Ave, Nashville, TN 37232-0146. E-mail inagamit{at}ctrvax.vanderbilt.edu
Background— The roles of angiotensin II (Ang II) in the regulation of heart function under normal and pathological conditions have been well documented. Although 2 types of Ang II receptor (AT1 and AT2) are found in various proportions, most studies have focused on AT1-coupled events. In the present study, we examined the hypothesis that signaling by AT2 is important to the development of left ventricular hypertrophy and cardiac fibrosis by Ang II infusion in mice lacking the AT2 gene (Agtr2-/Y).
Methods and Results— Male Agtr2-/Y and age-matched wild-type (WT) mice were treated long-term with Ang II, infused at a rate of 4.2 ng · kg-1 · min-1 for 3 weeks. Ang II elevated systolic blood pressure to comparable levels in Agtr2-/Y and WT mice. WT mice developed prominent concentric cardiac hypertrophy, prominent fibrosis, and impaired diastolic relaxation after Ang II infusion. In contrast, there was no cardiac hypertrophy in Agtr2-/Y mice. Agtr2-/Y mice, however, did not show signs of heart failure or impairment of ventricular relaxation and only negligible fibrosis after Ang II infusion. The absence of fibrosis may be a clue to the absence of impairment in ventricular relaxation and account for the normal left ventricular systolic and diastolic performances in Agtr2-/Y mice.
Conclusions— Chronic loss of AT2 by gene targeting abolished left ventricular hypertrophy and cardiac fibrosis in mice with Ang II–induced hypertension.
Key Words: angiotensin • collagen • heart failure • hypertrophy
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