Site-1 Protease-Derived Soluble (Pro)Renin Receptor Contributes to Angiotensin II-Induced Hypertension in Mice.

Abstract

Activation of PRR ([pro]renin receptor) contributes to enhancement of intrarenal RAS and renal medullary α-ENaC and thus elevated blood pressure during Ang II (angiotensin II) infusion. The goal of the present study was to test whether such action of PRR was mediated by sPRR (soluble PRR), generated by S1P (site-1 protease), a newly identified PRR cleavage protease. F1 B6129SF1/J mice were infused for 6 days with control or Ang II at 300 ng/kg per day alone or in combination with S1P inhibitor PF-429242 (PF), and blood pressure was monitored by radiotelemetry. S1P inhibition significantly attenuated Ang II-induced hypertension accompanied with suppressed urinary and renal medullary renin levels and expression of renal medullary but not renal cortical α-ENaC expression. The effects of S1P inhibition were all reversed by supplement with histidine-tagged sPRR termed as sPRR-His. Ussing chamber technique was performed to determine amiloride-sensitive short-circuit current, an index of ENaC activity in confluent mouse cortical collecting duct cell line cells exposed for 24 hours to Ang II, Ang II + PF, or Ang II + PF + sPRR-His. Ang II-induced ENaC activity was blocked by PF, which was reversed by sPRR-His. Together, these results support that S1P-derived sPRR mediates Ang II-induced hypertension through enhancement of intrarenal renin level and activation of ENaC.

• Authors: Ye Feng, Kexin Peng, Renfei Luo, Fei Wang, Tianxin Yang
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 77 Issue 2 Pg. 405-416 (02 2021) ISSN: 1524-4563 [Electronic] United States
• PMID: 33280408 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• PF-429242
• Pyrrolidines
• Receptors, Cell Surface
• Angiotensin II
• Proprotein Convertases
• Serine Endopeptidases
• membrane-bound transcription factor peptidase, site 1
• Renin
• Prorenin Receptor

Topics

• Angiotensin II (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Hypertension (chemically induced, genetics, metabolism)
• Mice
• Proprotein Convertases (antagonists & inhibitors)
• Pyrrolidines (pharmacology)
• Receptors, Cell Surface (genetics, metabolism)
• Renin (metabolism)
• Renin-Angiotensin System (drug effects)
• Serine Endopeptidases
• Prorenin Receptor