title: High salt intake damages the heart through activation of cardiac (pro) renin receptors even at an early stage of hypertension.
abstract: OBJECTIVE
  It has not yet been fully elucidated whether cardiac tissue levels of prorenin, renin and (P)RR are activated in hypertension with a high salt intake. We hypothesized that a high salt intake activates the cardiac tissue renin angiotensin system and prorenin-(pro)renin receptor system, and damages the heart at an early stage of hypertension.
  
  
  METHODS
  Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) received regular (normal-salt diet, 0.9%) and high-salt (8.9%) chow for 6 weeks from 6 to 12 weeks of age. The systolic blood pressure, plasma renin activity (PRA) and plasma angiotensin II concentration were measured, and the protein expressions of prorenin, (pro)renin receptor, angiotensinogen, angiotensin II AT1 receptor, ERK1/2, TGF-β, p38MAPK and HSP27 in the myocardium were investigated. The cardiac function was assessed by echocardiography, and histological analysis of the myocardium was performed.
  
  
  RESULTS
  The high-salt diet significantly increased the systolic blood pressure, and significantly reduced the PRA and plasma angiotensin II concentration both in the WKYs and SHRs. Cardiac expressions of prorenin, renin, (P)RR, angiotensinogen, angiotensin II AT1 receptor, phosphorylated (p)-ERK1/2, p-p38MAPK, TGF-β and p-HSP27 were significantly increased by the high salt diet both in the WKYs and SHRs. The high-salt diet significantly increased the interventricular septum thickness and cardiomyocyte size, and accelerated cardiac interstitial and perivascular fibrosis both in the WKYs and SHRs. On the other hand, dilatation of left ventricular end-diastolic dimension and impairment of left ventricular fractional shortening was shown only in salt loaded SHRs.
  
  
  CONCLUSIONS
  The high-salt diet markedly accelerated cardiac damage through the stimulation of cardiac (P)RR and angiotensin II AT1 receptor by increasing tissue prorenin, renin and angiotensinogen and the activation of ERK1/2, TGF-β, p38MAPK and HSP27 under higher blood pressure.
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Yuka
authors: Y
authors: Hayakawa
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Takuma
authors: T
authors: Aoyama
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Chiharu
authors: C
authors: Yokoyama
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Chihiro
authors: C
authors: Okamoto
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Hisaaki
authors: H
authors: Komaki
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Shingo
authors: S
authors: Minatoguchi
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Masamitsu
authors: M
authors: Iwasa
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Yoshihisa
authors: Y
authors: Yamada
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Itta
authors: I
authors: Kawamura
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Masanori
authors: M
authors: Kawasaki
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Kazuhiko
authors: K
authors: Nishigaki
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Atsushi
authors: A
authors: Mikami
authors: Department of Life Science, Gifu University, Yanagido, Gifu, Japan.
authors: Fumiaki
authors: F
authors: Suzuki
authors: Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors: Shinya
authors: S
authors: Minatoguchi
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004452:Echocardiography; D015870:Gene Expression; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000097:blood / Q000235:genetics; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D055551:HSP27 Heat-Shock Proteins; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D017673:Sodium Chloride, Dietary; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen; D000804:Angiotensin II; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D048051:p38 Mitogen-Activated Protein Kinases; D012083:Renin; D000093342:Prorenin Receptor