Abstract
Objectives In this study, we will determine the function of the interaction between AT(2)R and ACE, and AT(1)R 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 mu m) 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. AT(2)R antagonist (PD123319, 1 mu M) 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 mu M) 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 AT(1)R/ACE and AT(2)R/ACE complexes formation, and similar AT(1)R, AT(2)R, and ACE expression level in both groups. Conclusion The present findings show the existence of ACE/AT(2)R and ACE/AT(1)R complexes on endothelial cells and VSMC, respectively. ACE/AT(2)R complex plays a modulator effect on ACE/AT(1)R-SMC-induced contraction of MRA, which is altered in hypertension.