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Molecular and Cellular Biochemistry

, Volume 311, Issue 1–2, pp 1–7 | Cite as

Role of ACE/AT2R complex in the control of mesenteric resistance artery contraction induced by ACE/AT1R complex activation in response to Ang I

  • Jun Su
  • Desiree I. Palen
  • Hamid Boulares
  • Khalid Matrougui
Article

Abstract

Objectives In this study, we will determine the function of the interaction between AT2R and ACE, and AT1R and ACE in the control of mesenteric resistance artery (MRA) tone from normotensive (NT) and Angiotensin II (AII)-dependent hypertensive (HT) mice. Methods–results Hypertension was induced by infusion of Ang-II (200 ng/kg/day) for 3 weeks. Freshly MRA (100-120 μm) were isolated from HT and NT mice and mounted in an arteriograph. Dose–response of Ang-I induced a similar contraction of MRA from NT and HT mice, which was increased after endothelium removal. AT2R antagonist (PD123319, 1 μM) significantly increased Ang-I-induced contraction of MRA from NT but not from HT mice. In addition, PD123319 significantly increased in vivo blood pressure in response to Ang-I. Luminal incubation with ACE-antibody (50 ng/ml) to block only endothelial ACE function significantly enhanced Ang-I-induced contraction of MRA from NT mice. ACE inhibitor (captopril, 10 μM) completely blocked Ang-I-induced contraction of MRA from both animals and prevented the increased blood pressure. Freshly isolated MRA subjected to immunoprecipitation, Western blot analysis and RT-PCR revealed AT1R/ACE and AT2R/ACE complexes formation, and similar AT1R, AT2R, and ACE expression level in both groups. Conclusion The present findings show the existence of ACE/AT2R and ACE/AT1R complexes on endothelial cells and VSMC, respectively. ACE/AT2R complex plays a modulator effect on ACE/AT1R-SMC-induced contraction of MRA, which is altered in hypertension.

Keywords

Angiotensin II Angiotensin I AT1AT2ACE Resistance artery Contraction Hypertension 

Notes

Acknowledgments

This work was supported by American Heart Association SDG grant (0430278N, PI: Khalid Matrougui) and NIH-HL072889 (PI, Hamid Boulares).

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Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Jun Su
    • 1
  • Desiree I. Palen
    • 1
  • Hamid Boulares
    • 1
  • Khalid Matrougui
    • 1
  1. 1.Department of Pharmacology, LSU Health Sciences CenterTulane UniversityNew OrleansUSA

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