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.