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

Background - The roles of angiotensin II (Ang II) in the regulation of hear t function under normal and pathological conditions have been well document ed. Although 2 types of Ang II receptor (AT(1) and AT(2)) are found in vari ous proportions, most studies have focused on AT(1)-coupled events. In the present study, we examined the hypothesis that signaling by AT(2) is import ant to the development of left ventricular hypertrophy and cardiac fibrosis by Ang II infusion in mice lacking the AT(2) gene (Agtr2-/T). Methods and Results - Male Agrt2-/Y and age-matched wild-type (WT) mice wer e treated long-term with Ang II, infused at a rate of 4.2 ng (.) kg(-1 .) m in(-1)for 3 weeks. Ang II elevated systolic blood pressure to comparable le vels in Agtr2-/Y and WT mice. WT mice developed prominent concentric cardia c 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 impair ment of ventricular relaxation and only negligible fibrosis after Ang II in fusion. The absence of fibrosis may be a clue to the absence of impairment in ventricular relaxation and account for the normal left ventricular systo lic and diastolic performances in Agtr2-/Y mice. Conclusions - Chronic loss of AT(2) by gene targeting abolished left ventri cular hypertrophy and cardiac fibrosis in mice with Ang II-induced hyperten sion.