title: Renal arteriolar injury by salt intake contributes to salt memory for the development of hypertension.
abstract: The role of salt intake in the development of hypertension is prominent, but its mechanism has not been fully elucidated. Our aim was to examine the effect of transient salt intake during the prehypertensive period in hypertensive model animals. Dahl salt-sensitive rats and spontaneously hypertensive rats were fed from 6 to 14 weeks with low-salt (0.12% NaCl), normal-salt (0.8% NaCl), high-salt (7% NaCl), or high-sodium/normal-chloride diet and returned to normal-salt diet for 3 months. Rats in the high-salt group saw elevations in blood pressure (BP) not only during the treatment period but also for the 3 months after returning to normal-salt diet. We named this phenomenon salt memory. Renal arteriolar injury was found in the high-salt group at the end of experiment. Dahl salt-sensitive rats were fed from 6 to 14 weeks with high-salt diet with angiotensin receptor blocker, vasodilator, calcium channel blocker, and calcium channel blocker+angiotensin receptor blocker and returned to normal-salt diet. Although BP was suppressed to control levels by vasodilator or calcium channel blocker, elevated renal angiotensin II and renal arteriolar injury were observed, and salt memory did not disappear because of sustained renal arteriolar injury. Calcium channel blocker+angiotensin receptor blocker suppressed renal arteriolar injury, resulting in the disappearance of salt memory. Cross-transplantation of kidneys from Dahl salt-sensitive rats on high salt to control rats caused increase of BP, whereas control kidneys caused reduction in BP of hypertensive rats, inducing the central role of the kidney. These results suggest that renal arteriolar injury through BP and renal angiotensin II elevation plays important roles in the development of salt memory for hypertension.
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Hideyo
authors: H
authors: Oguchi
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan. sasamura@a8.keio.jp.
authors: Hiroyuki
authors: H
authors: Sasamura
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Kazunobu
authors: K
authors: Shinoda
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Shinya
authors: S
authors: Morita
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Hidaka
authors: H
authors: Kono
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Ken
authors: K
authors: Nakagawa
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Kimiko
authors: K
authors: Ishiguro
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Kaori
authors: K
authors: Hayashi
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Mari
authors: M
authors: Nakamura
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Tatsuhiko
authors: T
authors: Azegami
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Mototsugu
authors: M
authors: Oya
authors: From the Departments of Internal Medicine and Urology, School of Medicine, Keio University, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Itoh
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000633:toxicity; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D012083:Renin
keywords: hypertension; kidney transplantation; renin-angiotensin system; vascular system injuries