Abstract: SA-PO328
Urinary Plasmin Plays Pathogenic Roles for the Development of Hypertension in Dahl Salt-Sensitive Rats
Session Information
- Hypertension and CVD: Mechanisms
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Iwata, Yasunobu, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Kakizoe, Yutaka, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Deng, Qinyuan, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Nakagawa, Terumasa, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Adachi, Masataka, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Izumi, Yuichiro, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Kuwabara, Takashige, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
- Kitamura, Kenichiro, University of Yamanashi Faculty of Medicine, Yamanashi, Japan
- Mukoyama, Masashi, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
Background
The epithelial sodium channel (ENaC) in the renal collecting duct plays pivotal roles in the regulation of sodium homeostasis and blood pressure. The proteolytic cleavage of γENaC by extracellular serine proteases is an important process for the full activation of this channel and is physiologically regulated by aldosterone. In the setting of proteinuria, proteases filtered through damaged glomeruli could activate ENaC leading to hypertension, independently of aldosterone. We reported that Dahl salt-sensitive (DS) rats with high-salt (HS) diet developed severe hypertension together with aberrant activation of γENaC by serine proteases. However, the role of plasmin in the hypertension of DS rats remain to be elucidated. In this study, we evaluated the relationship of proteinuria, urinary plasmin activity and hypertension, and the antihypertensive effect of a serine protease inhibitor camostat mesilate (CM) in DS rats.
Methods
Four-week-old DS rats were divided into normal-salt (NS) diet, HS and HS+CM (0.1% diet) groups. After systolic BP measurement and 24h urine collection were performed for 5 weeks, rats were sacrificed for biochemical examination. Urinary plasmin activities were evaluated by zymography and Western blotting.
Results
HS diet induced severe hypertension [SBP (mmHg): NS, 141.1±5.8; HS, 222.3±15.4; HS+CM, 199.5±5.0], marked proteinuria [U-TP (mg/day): NS, 23.8±12.1; HS 272.3±79.9; HS±CM, 135.1±27.4] and urinary plasmin activation, as well as the cleavage of urinary exosomal γENaC. The treatment with CM suppressed these changes, together with significantly reduced BP and proteinuria.
Conclusion
In conclusion, plasmin is associated with the pathogenesis of hypertension in DS rats, and serine protease inhibition could be a potential therapeutic strategy against salt-sensitive hypertension with proteinuria.