Original Report: Laboratory Investigation

Heme-Oxygenase Upregulation Ameliorates Angiotensin II-Induced Tubulointerstitial Injury and Salt-Sensitive Hypertension
Ashok Pradhan, Michio Umezu, Masafumi Fukagawa

Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe, Japan

Address of Corresponding Author

Am J Nephrol 2006;26:552-561 (DOI: 10.1159/000098001)

  Key Words

• Heme oxygenase
• Hemin
• Hypertension
• Oxidative injury
• Salt sensitivity
• Tubulointerstitial injury

  Abstract

Background: Heme oxygenase-1 (HO-1) has been implicated in the modulation of several diseases including hypertension (HTN) and renal injury. The tubulointerstitial (TI) injuries are supposed to be the main determinants for the development of salt-sensitive HTN. Therefore, this study examined the role of HO-1 in angiotensin II (AngII)-induced TI injury and salt-sensitive HTN. Methods: Sprague-Dawley rats on a high salt diet were treated by AngII infusion plus either hemin, an inducer of HO-1, or hemin + zinc protoporphyrin, a HO-1 inhibitor, for 2 weeks, and then followed for 6 weeks. Results: The AngII infusion resulted in acute HTN and proteinuria. Light microscopy revealed focal areas of tubular atrophy with mononuclear cell infiltration and interstitial expansion. The overexpression of osteopontin and TGF-₁ accompanied by diminished expression of rat endothelial cell antigen-1, the hallmarks of TI injury, were observed. At 2 weeks, all interventions were withdrawn and systolic blood pressure returned towards normal. After a brief normal salt diet, rats were again placed on high salt diet, resulting in progressive increase in systolic blood pressure in the HO-1-inhibited group. Conclusion: The induction of HO-1 attenuated the development of HTN, suggesting that HO-1 plays a crucial role in significant attenuation of AngII-mediated TI injury and resultant salt-sensitive HTN.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Masafumi Fukagawa, MD, PhD, FJSIM, FASN
Division of Nephrology and Dialysis Center, Kobe University School of Medicine
7-5-2 Kusunoki-cho
Chuo-ku, Kobe 650-0017 (Japan)
Tel. +81 78 382 6500, Fax +81 78 382 6509, E-Mail fukagawa@med.kobe-u.ac.jp

  Article Information

Received: July 30, 2006
Accepted: November 13, 2006
Published online: December 13, 2006
Number of Print Pages : 10
Number of Figures : 7, Number of Tables : 1, Number of References : 46