Address of Corresponding Author

Kidney Blood Press Res 2005;28:134-143 (DOI: 10.1159/000085956)

  Key Words

• Angiotensin II
• Hypertrophy
• Transgenic rats
• Inflammation
• Coronary arteries
• Remodeling

  Abstract

Background:Blood pressure-independent (BP) effects of angiotensin (Ang) II and endothelin (ET) on coronaries (remodeling) in high renin hypertension are incompletely understood. Methods:We studied the effects of subdepressor doses of Ang II receptor (AT₁) blockade with losartan (10 mg/kg/day gavage) and endothelin A receptor (ET_A) blockade with LU135252 (30 mg/kg/day) on the coronaries of rats harboring human renin and angiotensinogen genes (dTGR). Nontransgenic Sprague-Dawley rats were controls. The rats were treated between the ages of 6 and 10 weeks. Coronary cross-sectional area [CSA; 0.79 × (external diameter² - internal diameter²)], cell proliferation, and infiltration of monocytes/macrophages were determined. Results:Monotherapy did not lower BP while combination treatment did (p < 0.05). All treatments reduced mortality (p < 0.01). CSA was decreased by all treatments compared to vehicle, independent of blood pressure (p < 0.05). Extensive proliferation by PCNA staining and infiltration of ED-1-positive cells was diminished by both treatment and the combination. Conclusions:The data show that Ang II promotes coronary inflammation and remodeling, in part independent of blood pressure but dependent upon ET signaling. Combination treatment directed at both pathways may improve outcome, independent of blood pressure reduction.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Dr. Stephan Gerbaulet
St. Martinus Hospital
Gladbacher Strasse 26
DE-40219 Düsseldorf (Germany)
Tel. +49 211 917 1289, Fax +49 211 917 1348, E-Mail s.gerbaulet@martinus-duesseldorf.de

  Article Information

Accepted: February 11, 2005
Published online: May 26, 2005
Number of Print Pages : 10
Number of Figures : 6, Number of Tables : 2, Number of References : 35