Article

Molecular and Cellular Biochemistry

, Volume 311, Issue 1, pp 1-7

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 SuAffiliated withDepartment of Pharmacology, LSU Health Sciences Center, Tulane University
  • , Desiree I. PalenAffiliated withDepartment of Pharmacology, LSU Health Sciences Center, Tulane University
  • , Hamid BoularesAffiliated withDepartment of Pharmacology, LSU Health Sciences Center, Tulane University
  • , Khalid MatrouguiAffiliated withDepartment of Pharmacology, LSU Health Sciences Center, Tulane University Email author 

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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 AT1R AT2R ACE Resistance artery Contraction Hypertension