title: Relaxin ameliorates salt-sensitive hypertension and renal fibrosis.
abstract: 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.
authors.affiliation: Department of Clinical Nutrition, School of Food and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kumagai
authors.forename: Ayumi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Sakae
authors.initials: S
authors.lastname: Ohkawa
authors.forename: Mari
authors.initials: M
authors.lastname: Odamaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kohsaka
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Ikegaya
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D005355:Fibrosis / Q000139:chemically induced / Q000517:prevention & control*; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012065:Relaxin / Q000627:therapeutic use*; D051785:Smad Proteins / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051785:Smad Proteins; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D012065:Relaxin; D019001:Nitric Oxide Synthase