title: Large blood pressure variability aggravates arteriolosclerosis and cortical sclerotic changes in the kidney in hypertensive rats.
abstract: BACKGROUND
  It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV. METHODS AND RESULTS: Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV.
  
  
  CONCLUSIONS
  Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV.
authors: Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine.
authors: Yuji
authors: Y
authors: Aoki
authors: Hisashi
authors: H
authors: Kai
authors: Hidemi
authors: H
authors: Kajimoto
authors: Hiroshi
authors: H
authors: Kudo
authors: Narimasa
authors: N
authors: Takayama
authors: Suguru
authors: S
authors: Yasuoka
authors: Takahiro
authors: T
authors: Anegawa
authors: Yoshiko
authors: Y
authors: Iwamoto
authors: Hiroki
authors: H
authors: Uchiwa
authors: Kenji
authors: K
authors: Fukuda
authors: Masayoshi
authors: M
authors: Kage
authors: Seiya
authors: S
authors: Kato
authors: Yoshihiro
authors: Y
authors: Fukumoto
authors: Tsutomu
authors: T
authors: Imaizumi
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D011918:Rats, Inbred SHR