Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats

• Published in: Journal of the renin-angiotensin-aldosterone system Vol. 15; no. 4; pp. 440 - 449
• Main Authors: Nagai, Yohko, Nakanishi, Kazushige, Akimoto, Tatsuo, Yamanaka, Nobuaki
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-12-2014
• Subjects: Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Arterioles - cytology; Arterioles - drug effects; Arterioles - ultrastructure; Cell Proliferation - drug effects; Immunohistochemistry; Kidney - blood supply; Kidney - drug effects; Male; Myocytes, Smooth Muscle - drug effects; Rats, Inbred SHR; Renin - metabolism; afferent arteriole; juvenile; angiotensin II receptor blocker; Renal pathology; smooth muscle cell hyperplasia
• ISSN: 1470-3203; 1752-8976
• DOI: 10.1177/1470320313502105

Introduction:
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.
Materials and 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 12th week. Increased renin expression and arteriolar changes were found from the 4th week in the juvenile SHR+ARB group.
Conclusion:
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.