High salt intake damages the heart through activation of cardiac (pro) renin receptors even at an early stage of hypertension

• Published in: PloS one Vol. 10; no. 3; p. e0120453
• Main Authors: Hayakawa, Yuka, Aoyama, Takuma, Yokoyama, Chiharu, Okamoto, Chihiro, Komaki, Hisaaki, Minatoguchi, Shingo, Iwasa, Masamitsu, Yamada, Yoshihisa, Kawamura, Itta, Kawasaki, Masanori, Nishigaki, Kazuhiko, Mikami, Atsushi, Suzuki, Fumiaki, Minatoguchi, Shinya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-03-2015; Public Library of Science (PLoS)
• Subjects: Activation; Angiotensin AT1 receptors; Angiotensin II; Angiotensin II - blood; Angiotensinogen; Angiotensinogen - genetics; Angiotensinogen - metabolism; Angiotensins; Animals; Blood; Blood Pressure; Body Weight; Bone morphogenetic proteins; Cardiology; Cardiomyocytes; Damage; Diet; Echocardiography; Fibrosis; Gene Expression; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - metabolism; Heart; Heart diseases; Heart Ventricles - metabolism; Heart Ventricles - pathology; Heat shock proteins; HSP27 Heat-Shock Proteins - genetics; HSP27 Heat-Shock Proteins - metabolism; Hsp27 protein; Hypertension; Hypertension - etiology; Hypertension - metabolism; Hypertension - pathology; Kidneys; Kinases; Laboratory animals; Lung - pathology; Male; Medical research; Medicine; Myocardium; Myocardium - metabolism; Myocardium - pathology; Nutrition research; Organ Size; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Plasma; Prorenin Receptor; Rats; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Renin; Renin - blood; Renin - genetics; Rodents; Salts; Septum; Signal Transduction; Sodium Chloride, Dietary - administration & dosage; Sodium Chloride, Dietary - adverse effects; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factors; University graduates; Ventricle; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120453

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.
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.
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.
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.