Effects of the selective chymase inhibitor TEI-F00806 on the intrarenal renin-angiotensin system in salt-treated angiotensin I-infused hypertensive mice.

Abstract

NEW FINDINGS:

What is the central question of this study? Can chymase inhibition prevent angiotensin I-induced hypertension through inhibiting the conversion of angiotensin I to angiotensin II in the kidney? What is the main finding and its importance? Treatment with TEI-F00806 decreased angiotensin II content of the kidney, renal cortical angiotensinogen protein levels and chymase mRNA expression, and attenuated the development of hypertension.

ABSTRACT:

The effects of the selective chymase inhibitor TEI-F00806 were examined on angiotensin I (Ang I)-induced hypertension and intrarenal angiotensin II (Ang II) production in salt-treated mice. Twelve-week-old C57BL male mice were given a high-salt diet (4% NaCl + saline (0.9% NaCl)), and divided into three groups: (1) sham + vehicle (5% acetic acid in saline), (2) Ang I (1 μg kg-1  min-1 , s.c.) + vehicle, and (3) Ang I + TEI-F00806 (100 mg kg-1  day-1 , p.o.) (n = 8-10 per group). Systolic blood pressure was measured weekly using a tail-cuff method. Kidney Ang II content was measured by radioimmunoassay. Chronic infusion of Ang I resulted in the development of hypertension (P < 0.001), and augmented intrarenal chymase gene expression (P < 0.05), angiotensinogen protein level (P < 0.001) and Ang II content (P < 0.01) in salt-treated mice. Treatment with TEI-F00806 attenuated the development of hypertension (P < 0.001) and decreased Ang II content of the kidney (P < 0.05), which was associated with reductions in renal cortical angiotensinogen protein levels (P < 0.001) and chymase mRNA expression (P < 0.05). These data suggest that a chymase inhibitor decreases intrarenal renin-angiotensin activity, thereby reducing salt-dependent hypertension.

• Authors: Tuba M Ansary, Maki Urushihara, Yoshihide Fujisawa, Sayaka Nagata, Hidenori Urata, Daisuke Nakano, Hitomi Hirofumi, Kazuo Kitamura, Shoji Kagami, Akira Nishiyama
• Journal: Experimental physiology (Exp Physiol) Vol. 103 Issue 11 Pg. 1524-1531 (11 2018) ISSN: 1469-445X [Electronic] England
• PMID: 30137655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Chemical References

• Angiotensin II
• Angiotensin I
• Peptidyl-Dipeptidase A
• Chymases

Topics

• Angiotensin I
• Angiotensin II (metabolism)
• Animals
• Blood Pressure (drug effects)
• Chymases (antagonists & inhibitors, metabolism)
• Hypertension (chemically induced, drug therapy, metabolism)
• Kidney (drug effects, metabolism)
• Male
• Mice
• Peptidyl-Dipeptidase A (metabolism)
• Renin-Angiotensin System (drug effects)