Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system

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Authors

Wang, Fei
Lu, Xiaohan
Liu, Mi
Feng, Yumei
Zhou, Shu-Feng
Yang, Tianxin

Issue Date

2015

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Article

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Keywords

(Pro)renin receptor , Angiotensin II , Renin activity , pro20 , Vascular smooth muscle cells

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Abstract

(Pro) renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro. Within the kidney, PRR is highly expressed in the renal medulla where its expression is induced by angiotensin II infusion. The objective of the present study was to test a potential role of renal medullary PRR during angiotensin II-induced hypertension. Methods: A rat AngII infusion model (100 ng/kg/min) combined with renal intramedullary infusion of PRO20, a specific inhibitor of PRR, was builded. And the intravenous PRO20 infusion serve as control. Mean arterial pressure was recorded by radiotelemetry for one week. Further anaylsis of kidney injury, inflammation, biochemical indices and protein localization were perrformed in vivo or in vitro. Results: Radiotelemetry demonstrated that AngII infusion elevated the mean arteria pressure from 108 +/- 5.8 to 164.7 +/- 6.2 mmHg. Mean arterial pressure decreased to 128.6 +/- 5.8 mmHg (P < 0.05) after intramedullary infusion of PRO20, but was only modestly affected by intravenous PRO20 infusion. Indices of kidney injury, including proteinuria, glomerulosclerosis, and interstitial fibrosis, inflammation, and increased renal medullary and urinary renin activity following angiotensin II infusion were all remarkably attenuated by intramedullary PRO20 infusion. Following one week of angiotensin II infusion, increased PRR immunoreactivity was found in vascular smooth muscle cells. In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20. Conclusion: Renal medullary PRR mediates angiotensin II-induced hypertension, likely by amplifying the local renin response.

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Wang, F., Lu, X., Liu, M., Feng, Y., Zhou, S.-F., & Yang, T. (2015). Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin–angiotensin system. BMC Medicine, 13(1). doi:10.1186/s12916-015-0514-1

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ISSN

1741-7015

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