Large Blood Pressure Variability Aggravates Arteriolosclerosis and Cortical Sclerotic Changes in the Kidney in Hypertensive Rats

Yuji Aoki; Hisashi Kai; Hidemi Kajimoto; Hiroshi Kudo; Narimasa Takayama; Suguru Yasuoka; Takahiro Anegawa; Yoshiko Iwamoto; Hiroki Uchiwa; Kenji Fukuda; Masayoshi Kage; Seiya Kato; Yoshihiro Fukumoto; Tsutomu Imaizumi

doi:10.1253/circj.CJ-14-0027

Hypertension and Circulatory Control

Large Blood Pressure Variability Aggravates Arteriolosclerosis and Cortical Sclerotic Changes in the Kidney in Hypertensive Rats

Yuji Aoki, Hisashi Kai, Hidemi Kajimoto, Hiroshi Kudo, Narimasa Takayama, Suguru Yasuoka, Takahiro Anegawa, Yoshiko Iwamoto, Hiroki Uchiwa, Kenji Fukuda, Masayoshi Kage, Seiya Kato, Yoshihiro Fukumoto, Tsutomu Imaizumi

Author information

Yuji Aoki
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Hisashi Kai
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Hidemi Kajimoto
Cardiovascular Research Institute, Kurume University
Hiroshi Kudo
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Narimasa Takayama
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Suguru Yasuoka
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Takahiro Anegawa
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Yoshiko Iwamoto
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Hiroki Uchiwa
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Kenji Fukuda
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Masayoshi Kage
Department of Diagnostic Pathology, Kurume University Hospital
Seiya Kato
Division of Pathology, Saiseikai Fukuoka General Hospital
Yoshihiro Fukumoto
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
Tsutomu Imaizumi
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine
International University of Health and Welfare, Fukuoka Sannno Hospital

Keywords: Angiotensin, Blood pressure variability, Hypertension, Kidney, Remodeling

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Supplementary material

2014 Volume 78 Issue 9 Pages 2284-2291

DOI https://doi.org/10.1253/circj.CJ-14-0027

Editorial (78-9 pp.2162-2163)

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Details

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. (Circ J 2014; 78: 2284–2291)

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