Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats.
BACKGROUND
Our previous study of angiotensin II receptor blocker (ARB) administration in rats induced unusual proliferative changes of smooth muscle cells in renal arteriolar walls. The present study examined if the incidence of the changes depended on the rats' age, and how long it would take to find changes.


METHODS
Six-week-old (juvenile spontaneous hypertensive rats (SHRs)+ARB group, n=15) and 20-week-old (adult SHRs+ARB group, n=10) male SHRs were fed a standard diet (0.4% NaCl) containing valsartan (10 mg/kg/day; Novartis Co.). Fifteen age-matched SHRs were studied as controls. After 4, 8, and 12 weeks, the rat kidneys were examined under light and electron microscopes and through immunohistochemical studies.


RESULTS
Extremely concentric proliferative changes in afferent arteriolar walls were frequently observed in the juvenile SHR+ARB group compared to the adult SHR+ARB group (48.7±6.8% vs 19.3±6.9%; p=0.0307) at the 12(th) week. Increased renin expression and arteriolar changes were found from the 4(th) week in the juvenile SHR+ARB group.


CONCLUSIONS
This study indicates that ARB administration induces unusual proliferative changes and a marked renin-producing cell increase in afferent arterioles more frequently in juveniles than adult rats. It is suggested that the treatment of ARB in juveniles might have a higher risk of changes in renal afferent arterioles.
Tokyo Kidney Research Institute, Tokyo, Japan Department of General Medicine and Emergency Care, Faculty of Medicine, Toho University, Tokyo, Japan nagai.y@tkri.jp.
Yohko
Y
Nagai
Department of General Medicine and Emergency Care, Faculty of Medicine, Toho University, Tokyo, Japan.
Kazushige
K
Nakanishi
Department of General Medicine and Emergency Care, Faculty of Medicine, Toho University, Tokyo, Japan.
Tatsuo
T
Akimoto
Tokyo Kidney Research Institute, Tokyo, Japan.
Nobuaki
N
Yamanaka
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011918:Rats, Inbred SHR; D012083:Renin / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D012083:Renin
Renal pathology; afferent arteriole; angiotensin II receptor blocker; juvenile; smooth muscle cell hyperplasia