Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension.

Ichihara S, Senbonmatsu T, Price E, Ichiki T, Gaffney FA, Inagami T
Circulation. 2001 104 (3): 346-51

PMID: 11457756 · DOI:10.1161/01.cir.104.3.346

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 (AT(1) and AT(2)) are found in various proportions, most studies have focused on AT(1)-coupled events. In the present study, we examined the hypothesis that signaling by AT(2) is important to the development of left ventricular hypertrophy and cardiac fibrosis by Ang II infusion in mice lacking the AT(2) 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 AT(2) by gene targeting abolished left ventricular hypertrophy and cardiac fibrosis in mice with Ang II-induced hypertension.

MeSH Terms (24)

Angiotensin II Animals Chronic Disease Collagen Diastole Disease Models, Animal Echocardiography Echocardiography, Doppler Endomyocardial Fibrosis Fibronectins Hypertension Hypertrophy, Left Ventricular Male Mice Mice, Inbred C57BL Mice, Knockout Myocardium Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin RNA, Messenger Systole Transforming Growth Factor beta Transforming Growth Factor beta1

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