Objectives: Hypertension is an important risk factor in cardiovascular disease that is related with several mechanisms including reactive oxygen species (ROS). Previously our studies showed that, telmisartan (TERT) or carvedilol (CVDL) improved cardiovascular oxidation and endothelial progenitor cell (EPC) function in spontaneously hypertensive rats (SHRs). The purpose of this study was to compare the modulating effect of CVDL, an antioxidant beta-blocker (BB) and TERT, an angiotensin receptor blocker (ARB) on cardiovascular oxidation and EPCs functional regulation in SHRs.
Methods and Results: Animals were divided into following five groups, eight-weeks-old WKY rats (n=6), untreated SHR group (n=8), treated with diuretic (tricholorothiazide, 1.6mg/kg/day, n=8), BB (carvediolol, 30mg/kg/day, n=8) and ARB (telmisartan, 5mg/kg/day, n=8) in SHR for fourteen days. After medication, blood pressures, heart rates and aortic wall thickness were measured. Tissue oxidative stress was evaluated by dihydroethidium (DHE) stain and malondialdehyde (MDA) was evaluated by TBARS assay. NADPH oxidase subunit complex (Mox-1, p22phox, p47phox and p67phox) expression and glutathione peroxidase-1 (GPx-1), an antioxidant enzyme expression were determined by western blot. EPC functional assay was done by EPC colony assay and tube network forming assay. ARB decreased aortic wall thickness (p<0.01) and expression of Mox-1 (p<0.05), p22phox (p<0.01) and p67phox (p<0.05). ARB markedly reduced the density of DHE in heart and aortic tissue, and the concentration of MDA in heart was compared with BB or diuretic-treated group (p<0.01). ARB and BB significantly reduced the expression of GPx1 in heart (p<0.05) and aorta (p<0.01) compared with control groups. The relative cardiac MDA suppression ratio/antioxidant GPx1 expression ratio was significantly higher in ARB-treated group. ARB and BB notably increased the number of EPC colonies and total tube length compared with SHR (p<0.01).
Conclusion: These results suggest that TERT, an ARB, may have better modulating effect on cardiovascular oxidation and EPCs function than CVDL in SHRs.

Keywords: TERT, CVDL, ROS, NADPH oxidase, GPx-1, EPC, SHR