Effect of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension.

摘要

OBJECTIVE: It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mechanisms such as a reduction in oxidative stress is not clear. We investigated the influence of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension. METHODS: Thirteen patients were included in this randomized, double-blind, crossover study; they received losartan 50 mg twice daily for 4 weeks followed by atenolol 50 mg twice daily or vice versa. Concomitant medication with renin-angiotensin blocking agents or beta-blockers was withdrawn, whereas other medication remained unchanged. At baseline and after each treatment period, flow-mediated dilation of the brachial artery and oxidative stress were measured in serum samples. RESULTS: Flow-mediated dilation was increased significantly after 4 weeks' treatment with losartan (3.4 +/- 0.44%) compared with atenolol (2.58 +/- 0.42%; P = 0.01). 8-Isoprostanes, a marker of oxidative stress, were significantly reduced in the losartan group compared with baseline (0.039 +/- 0.007 versus 0.067 +/- 0.006 ng/ml; P = 0.01), but did not differ from baseline with atenolol. Glucose, hemoglobin A1c, highly sensitive C-reactive protein, lipids and systolic blood pressure remained unaltered, whereas diastolic blood pressure tended to be lower in the atenolol group. CONCLUSIONS: This study demonstrates that losartan significantly improved endothelial function in type 2 diabetes patients with hypertension compared with atenolol. This must be independent of the blood pressure-lowering effect of losartan and is probably caused by an antioxidative effect of the angiotensin receptor blocker.