BACKGROUND AND PURPOSE: @entity120 ( @entity120 ) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to @entity712 and @entity204 . A dysregulated renin angiotensin system (RAS) has been implicated in the development and progression of @entity120 . However, the role of the angiotensin type II receptor (AT2 receptor) in @entity120 has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established @entity6560 (MCT) @entity35 model of @entity120 . EXPERIMENTAL APPROACH: A single subcutaneous injection of MCT (50 mg/kg) was used to induce @entity120 in 8-week-old male @entity35 . After 2-weeks of MCT administration, a subset of animals began receiving, either 0.03mg/kg C21, 3mg/kg @entity11083 , 0.5mg/kg A779 for an additional 2-weeks, after which right-ventricular hemodynamic parameters were measured and tissues collected for gene expression and histological analyses. KEY RESULTS: Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced @entity120 . Most notably, C21 reversed pulmonary @entity82 and prevented right ventricular @entity82 . These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro-inflammatory cytokines, and favorable modulation of the lung RAS. Conversely, co-administration of the AT2 receptor antagonist, @entity11083 , or the Mas antagonist, A779, completely abolished the protective actions of C21. CONCLUSIONS AND INDICATIONS: Collectively, our results suggest that the AT2 receptor agonist, C21, may hold promise for @entity1 with @entity120 .

Selective Activation of At2 Receptor Attenuates Progression of Pulmonary Hypertension and Inhibits XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity712 :: ('MESH:D006333', 'Disease') :: ['right heart failure'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity11083 :: ('MESH:C073402', 'Chemical') :: ['PD-123319'] @entity6560 :: ('MESH:D016686', 'Chemical') :: ['monocrotaline'] @entity120 :: ('MESH:D006976', 'Disease') :: ['Pulmonary hypertension', 'PH'] @entity35 :: ('10116', 'Species') :: ['rat', 'Sprague Dawley rats'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity82 :: (MESH:D005355,Disease) :: ['Cardiopulmonary Fibrosis']
