Background and Purpose; Recent reports suggested that beta blockers and angiotensin receptor blocker (ARB) affect against cardiovascular oxidation and endothelial progenitor cell (EPC) senescence in hypertensive rats. The purpose of this study was to directly compare the antioxidant effect and EPC functional regulation of beta-blocker: atenolol (ATEL), nebivolol (NEBL), carvedilol (CVDL) and ARB: telmisartan (TERT).
Materials & Methods; There were eight experimental groups: WKY rat (normal control, n=6), untreated SHR (control group, n=9), TEMP-treated (5mg/kg/day, antioxidant: tempol, n=9), TCTZ-treated (1.6mg/kg/day, diuretic: tricholorothiazide, n=9), ATEL-treated (25mg/kg/day, n=9), NEBL-treated (5mg/kg/day, n=9), CVDL-treated (30mg/kg/day, n=9) and TERT-treated (5mg/kg/day, n=9). All groups were treated with their respective drugs for 14 days. We analyzed the hemodynamics (blood pressure, heart rates), tissue anatomy (aortic wall thickness), tissue oxidative stress (DHE stain, TBARS assay), NADPH oxidase expression (p22phox, p47phox), and EPC function (EPC-CFU hill assay).
Results; Blood pressure and aortic wall thickness were similarly reduced after being treated with antihypertensive drugs (p<0.01). DHE fluorescence density was markedly increased in untreated SHR (average +Δ 4.8 folds, vs. WKY). The increased DHE fluorescence density was significantly reduced after drug administration (average TEMP; -Δ2.3 fold, TCTZ; -Δ1.5, ATEL; -Δ1.9, NEBL; -Δ2.2, CVDL; -Δ2.7, TERT; -Δ3.54, vs. SHR). MDA concentration was reduced after treatment (TEMP; -Δ18%, TCTZ; -Δ4.4%, ATEL; -Δ5.8%, NEBL; -Δ20%, CVDL; -Δ22.7%, TERT; -Δ27.2% vs. SHR). NADPH oxidase subunits (p22phox and p47phox) were markedly reduced after CVDL and TERT treatment (p<0.005). These protein expressions in the heart, aorta and kidney were reduced in different degrees after the administrations with study drugs. The functionally reduced EPC of SHR was dramatically increased to form EPC hills after being administered with study drugs.
Conclusion; Telmisartan followed by carvedilol among beta blockers showed the higher improvement of EPC function through beyond blood pressure lowering properties in hypertension model.
Keywords; Hypertension, EPC, ROS, telmisartan, carvedilol.
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