Crucial Role of Rho-nuclear Factor-kappab Axis in Angiotensin Ii-induced Renal Injury.
From: Dept. of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112-2699, USA.
American journal of physiology. Renal physiology
- Publish Date: Jul 2007
- ISSN: 0363-6127
- Volume: 293
- Issue: 1
- Pages: F100-9
- Medium: Print
- Language: English
- Citation (JAMA): Ozawa Yuri, Kobori Hiroyuki, et al. Crucial Role of Rho-nuclear Factor-kappab Axis in Angiotensin Ii-induced Renal Injury.. Am. J. Physiol. Renal Physiol. Jul 2007;293:F100-9
Abstract
This study was performed to determine the effectiveness of the Rho kinase inhibitor and NF-kappaB inhibitor in renal injury of ANG II-infused hypertensive rats. Male Sprague-Dawley rats, maintained on a normal diet, received either a sham operation (n = 7) or continuous ANG II infusion (120 ng/min) subcutaneously via minipumps. The ANG II-infused rats were further subdivided into three subgroups (n = 7 each) to receive one of the following treatments during the entire period: vehicle, Rho kinase inhibitor (fasudil; 3 mg.kg(-1).day(-1) ip), or NF-kappaB inhibitor (parthenolide; 1 mg.kg(-1).day(-1) ip). After 12 days of ANG II infusion, systolic blood pressure (BP; 208 +/- 7 vs. 136 +/- 3 mmHg), Rho kinase activity, NF-kappaB activity, renal ANG II contents (160 +/- 25 vs. 84 +/- 14 pg/g), monocytic chemotactic protein (MCP) 1 mRNA, interstitial macrophage infiltration, transforming growth factor-beta1 (TGF-beta1) mRNA, interstitial collagen-positive area, urinary protein excretion (43 +/- 6 vs. 11 +/- 2 mg/day), and urinary albumin excretion were significantly enhanced compared with the Sham group. While fasudil or parthenolide did not alter systolic BP (222 +/- and 190 +/- 21, respectively), both treatments completely blocked ANG II-induced enhancement of NF-kappaB activity, renal ANG II contents (103 +/- 11 and 116 +/- 21 pg/g, respectively), MCP1 mRNA, interstitial macrophage infiltration, TGF-beta1 mRNA, interstitial collagen-positive area, urinary protein excretion (28 +/- 6 and 23 +/- 3 mg/day, respectively), and urinary albumin excretion. Importantly, parthenolide did not alter ANG II-induced Rho kinase activation although fasudil abolished ANG II-induced Rho kinase activation. These data indicate that the Rho-NF-kappaB axis plays crucial roles in the development of ANG II-induced renal injury independently from BP regulation.
Mesh Headings (Keywords): Angiotensin II, Animals, Anti-Inflammatory Agents, Non-Steroidal, Blood Pressure, Blotting, Western, Body Weight, Chemokine CCL2, Collagen, Electrophoretic Mobility Shift Assay, Hypertension, Renal, Kidney, Macrophages, Male, Monocytes, NF-kappa B, Proteinuria, RNA, Messenger, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Rho Factor, Sesquiterpenes, Transcription Factor RelA, Transforming Growth Factor beta1, Vasoconstrictor Agents
Check for Full Text / PubMed Unique Identifier (PMID): 17409276
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