Journal Article

Relaxin ameliorates salt-sensitive hypertension and renal fibrosis

Takuya Yoshida, Hiromichi Kumagai, Ayumi Suzuki, Natsuki Kobayashi, Sakae Ohkawa, Mari Odamaki, Tetsuya Kohsaka, Tatsuo Yamamoto and Naoki Ikegaya

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 6, pages 2190-2197
Published in print June 2012 | ISSN: 0931-0509
Published online November 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr618
Relaxin ameliorates salt-sensitive hypertension and renal fibrosis

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Background.

Although relaxin (RLX) has potent vasodilatory and anti-fibrotic properties, there is no information on its effects on salt-sensitive hypertension.

Methods.

We investigated the effects of short-term treatment with RLX on blood pressure (BP) and nitric oxide synthase (NOS) protein in the kidneys of male Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats after 1 week consumption of an 8% NaCl diet. We also evaluated the inhibitory effects of each specific NOS inhibitor on BP during 1-week RLX treatment under high-salt diet. Next, we examined the long-term effects of RLX treatment for 6 weeks on renal histology and transforming growth factor-beta1 (TGF-β1) expression in male DS and DR rats placed on the 8-week high-salt diet.

Results.

The short-term RLX treatment significantly attenuated the high-salt diet-induced rise in BP in DS rats with increasing neuronal NOS and endothelial NOS protein in kidneys. Selective inhibition of each of the three NOS isoforms significantly blocked the anti-hypertensive effects of RLX in DS rats after 1-week high-salt diet. The long-term treatment of DS rats with RLX for 6 weeks significantly reduced systolic BP, lessened glomerular and tubulointerstitial changes and reduced TGF-β signaling compared to saline-treated controls.

Conclusions.

The results suggested that RLX converted salt sensitivity to salt resistance, at least in part, by up-regulating NOS. RLX is a potentially useful therapeutic agent for salt-sensitive hypertension.

Keywords: NOS; TGF-β; SMAD

Journal Article.  4876 words.  Illustrated.

Subjects: Nephrology

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