NDT Advance Access published online on November 9, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl632
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1 The Lipid Research Laboratory, The Bruce Rappaport Faculty of Medicine, Technion, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel
* To whom correspondence should be addressed. Background. Hypertension is a major risk factor for cardiovascular disease and the renin-angiotensin-aldosterone system (RAAS) plays a central pathophysiological role in its formation. Angiotensin-converting enzyme (ACE) and its homologue ACE2 control the formation of counteracting effectors, angiotensin II (AngII), a potent vasopressor and Ang-(1-7) which has vasodilatory action. It is therefore hypothesized that the balance of the activities of these two enzymes, ACE and ACE2, could be important for the control of blood pressure (BP). Methods. Monocyte-derived macrophages were isolated from blood samples of normotensives (NT), prehypertensives (preHTN) and untreated hypertensive (HTN) male patients (n = 28, 18 and 11, respectively). The activities of ACE2 were determined by measuring leucine or phenylalanine released following hydrolysis of Ang I and Ang II, respectively. The activity of ACE was measured using a synthetic substrate. Results. The levels of BP were 112.6 ± 1.4/74.8 ± 1.2, 128.3 ± 0.8/78.1 ± 1.2 and 151.4 ± 2.7/99.3 ± 2.4 mmHg in the NT, preHTN and HTN, respectively (P < 0.001). The ACE2-mediated Ang II degrading activity (ACE2-II) was 1201 ± 241 fmol/min/mg cell protein in NT subjects and was significantly (P < 0.01) increased by 2.4-fold in preHTN. ACE2-II activity in HTN and NT was not significantly different. ACE2-mediated Ang I hydrolysis (ACE2-I) was 85-fold lower than the ACE2-II activity. ACE activity in the human monocyte-derived macrophages (HMDM) averaged 21.6 ± 3.0 mU/mg cell protein and did not differ among the three groups. Conclusions. PreHTN subjects have higher ACE2-II activity compared with HTN subjects, suggesting a protective role for ACE2 in the early stage of HTN development, probably by accelerated degradation of the vasopressor AngII.
Received May 4, 2006
Accepted October 4, 2006
Brief Report
ACE2 activity is increased in monocyte-derived macrophages from prehypertensive subjects
Shlomo Keidar 1 *, Alexander Strizevsky 1, Ayelet Raz 1, and Aviva Gamliel-Lazarovich 1
Shlomo Keidar, E-mail: skeidar{at}rambam.health.gov.il
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