Effects of the Oral Angiotensin II Type 2 Receptor Agonist C21 in Sugen-Hypoxia Induced Pulmonary Hypertension in Rats

Abstract

Substantial evidence supports the involvement of the renin-angiotensin system in pulmonary hypertension (PH), and the angiotensin II type 2 receptor (AT2R) is known to exert tissue protective actions. The effect of the selective AT2R agonist C21 (also known as Compound 21 or buloxibutid) was evaluated in the rat Sugen-hypoxia PH model. After a single injection of Sugen 5416 and hypoxia for 21 days, C21 (2 or 20 mg/kg) or vehicle was administered perorally twice daily from Day 21 to Day 55. On Day 56, hemodynamic assessments were performed, and lung and heart tissue were prepared for quantification of cardiac and vascular remodeling and fibrosis. Treatment with C21 20 mg/kg improved cardiac output and stroke volume and decreased right ventricular hypertrophy (all p 100 μm (all p 2R agonists may have a role in Group 1 and 3 PH treatment.

Keywords

• pulmonary hypertension
• vascular remodeling
• pulmonary fibrosis
• renin-angiotensin system
• angiotensin type 2 receptor agonist
• C21