Reduced NO production rapidly aggravates renal function through the NF-κB/ET-1/ETA receptor pathway in DOCA-salt-induced hypertensive rats

Life Sciences
Kimihiro KimuraYasuo Matsumura

Abstract

It has been reported that endothelin-1 (ET-1) overproduction and reduced nitric oxide (NO) production are closely related to the progression of renal diseases. In the present study, we examined the interrelation between ET-1 and NO system using rats treated with the combination of deoxycorticosterone acetate (DOCA)-salt and a non selective NO synthase inhibitor N(ω)-nitro-L-arginine (NOARG). Rats were treated with DOCA-salt (15 mg/kg, plus drinking water containing 1% NaCl) for two weeks, and then additional treatment of NOARG (0.6 mg/ml in the drinking water) was performed for three days. Combined treatment of DOCA-salt and NOARG drastically developed the severe renal dysfunction and tissue injury. This treatment additionally enhanced renal ET-1 production compared to the rats treated with DOCA-salt alone, whereas a selective ET(A) receptor antagonist ABT-627 completely prevented renal dysfunction and tissue injury. On the other hand, combined treatment of DOCA-salt and NOARG induced the phosphorylation of inhibitory protein kappa B (IκB), followed by the activation of nuclear factor-kappa B (NF-κB) in the kidney. In addition, pyrrolidine-dithiocarbamate completely suppressed not only NF-κB activation but also renal dysfunctio...Continue Reading

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Citations

Jun 19, 2013·Nature Reviews. Nephrology·Nancy J Brown
May 19, 2020·Matrix Biology : Journal of the International Society for Matrix Biology·Mohammad AlQudahMichael P Czubryt
Feb 6, 2020·Kidney Diseases·Rupesh RainaKirsten Kusumi

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