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The renin-angiotensin system (RAS) plays an important role in cardiac remodeling. Ang II induces cardiac hypertrophy and fibrosis in hypertension. Recently, some findings support the (pro)renin-(Pro)renin receptor (P)RR interaction at exceptionally high (pro)renin levels in vitro. However, the precise mechanisms of the (P)RR signaling in the heart remain obscure. The aim of this study was to investigate the roles of cardiac (P)RR and its downward signals on mean arterial pressure (MAP) in rats with abdominal aortic constriction, following treatment of handle region peptide (HRP) and phospholipase C-β3 (PLC-b3) inhibitor, U73122.
Seventy-five SD rats were divided into 5 groups (n=15 each group) as following: sham operated (SO), rats with the aortic ligation (AL), AL rats were given HRP (4μg kg-1 d-1, SC), AL rats given U73122 (40μg kg-1 d-1, SC) and AL rats given HRP+U73122. MAP was recorded using a tail-cuff method. After 4 weeks of treatment, levels of (P)RR, PLC-b3, PKC-a, ERK1/2 and Raf-1 in the heart were examined by RT-PCR and western blot.
The levels of (P)RR and PLC-b3 significantly increased in the left ventricle in hypertensive rats (P<0.01), respectively. MAP rose markedly (P<0.01). HRP decreased the level of (P)RR and U73122 suppressed PLC-b3 expression. Treatment of both HRP and U73122 significantly decreased levels of PKC-a, ERK1/2 and Raf-1 in the heart (P<0.001). Meanwhile, MAP was decreased after treatment.
This study demonstrates that (P)RR inhibitor, HRP and PLC-b3 inhibitor, U73122 decreased levels of (P)RR, PLC-b3, PKC-a, ERK1/2 and Raf-1 in the heart. Meanwhile, administration of both reagents lowered MAP. These findings indicate that cardiac (P)RR may activate PLC-b3, PKC, ERK1/2 and Raf-1 signals and lead to hypertension.
This study was supported by Science and Technology Department of Shandong Province (No.2016GSF201207) and the Natural Science Foundation of China (No. 81270336).