Abstract 406: Improved Angiotensin II Type 2 Receptor Expression and Function in Transglutaminase 2 Knock-Out Mice Treated with Angiotensin II

Objective: Transglutaminase 2 (TG2) induces transamidation and cross-linking of proteins that can modulate receptor interaction. Angiotensin II (AngII) may regulate TG2 and AngII type 2 receptor (AT2) expression and function. We hypothesized that AngII may impair AT2 expression and function through TG2. Methods: TG2-knockout mice (TG2-K/O, 8 weeks old, 6 for each group) and age-matched wild type (WT) mice were treated or not with AngII (400 ng/kg/min) for 14 days. Vascular reactivity was assessed in response to sodium nitroprusside (SNP, 10 nM to 1 mM), in mesenteric arteries pre-contracted with norepinephrine (10 μM). AT2 function was assessed by concentration-response curve to the selective AT2 agonist Compound 21 (C21, 1nM to 1 μM) in mesenteric arteries pre-contracted with norepinephrine. AT2 expression in aorta was evaluated by immunoblotting. Results: C21-induced relaxation was similar in untreated WT, and in untreated TG2-K/O. C21-induced relaxation was improved only in AngII-treated TG2-K/O (2-fold increase vs untreated TG2-K/O, P Conclusions: AngII fails to reduce AT2 expression and function in TG2-K/O mice. Therefore, AngII may negatively modulate AT2 receptor expression and function through TG2.