Angiotensin II Type 2 Receptor Expression After Vascular Injury
Open Access
- 1 November 2006
- journal article
- research article
- Published by Wolters Kluwer Health in Hypertension
- Vol. 48 (5), 942-949
- https://doi.org/10.1161/01.hyp.0000241061.51003.b7
Abstract
It has been suggested that the effects of angiotensin II type 1 receptor (AT 1 R) blockers are in part because of angiotensin II type 2 receptor (AT 2 R) signaling. Interactions between the AT 2 R and kinins modulate cardiovascular function. Because AT 2 R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT 1 R blocker valsartan and the ACE inhibitor benazepril require AT 2 R signaling through the bradykinin 1 and 2 receptors (B 1 R and B 2 R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT 2 R inhibitor), valsartan+des-arg 9 -[Leu 8 ]-bradykinin (B 1 R inhibitor), valsartan+HOE140 (B 2 R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT 2 R, B 1 R, or B 2 R in the presence of valsartan prevented the reduction seen with valsartan alone. B 2 R blockade inhibited the effect of benazepril. Injury increased AT 1 R, AT 2 R, B 1 R, and B 2 R expression. Treatment with valsartan but not benazepril significantly increased intima AT 2 R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT 2 R, B 1 R, and B 2 R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT 2 R, B 1 R, and B 2 R. Results suggest that AT 2 R expression and increased cGMP represent a molecular mechanism that differentiates AT 1 R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.Keywords
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