Enhanced platelet release of superoxide anion in systemic hypertension:: role of AT1 receptors

Background: enhanced oxidative stress has been observed in hypertension, but the underlying mechanism has not been fully clarified. Objective to study the relationship between oxygen free radicals and hypertension, using platelets as a tool to measure the cellular production of superoxide anion (O-2(-)). Design forty patients with hypertension were allocated randomly to groups to receive either irbesartan, an inhibitor of angiotensin II type 1 (AT(1)) receptors (n = 20), or a diuretic (hydrochlorothiazide) (n = 20). In each patient, collagen-induced production of O-2(-) by platelets was studied before and after 4 weeks of treatment. Forty sex- and age-matched healthy individuals were studied as controls. Methods: platelet-produced O-2(-) was measured using lucigenin chemiluminescence and hydroethidine cytofluorimetric analysis. Results: compared with healthy individuals, patients with hypertension showed a greater production of O-2(-) by platelets (P < 0.001); there was no correlation between blood pressure and platelet O-2(-) production. After treatment, no changes in platelet O-2(-) formation were observed in patients receiving hydrochlorothiazide; conversely, those treated with irbesartan showed a significant (P < 0.001) decrease in platelet O-2(-) production. At the end of the treatment, no differences in blood pressures were observed between the two groups. In-vitro incubation of platelets with angiotensin II elicited a significant increase in O-2(-) (P < 0.001) that was dose-dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of NADPH oxidase. Conclusion: patients with hypertension showed an enhanced formation Of O-2(-) in platelets that was not dependent on blood pressure but could be mediated by AT(1) receptors via NADPH oxidase activation. (C) 2004 Lippincott Williams Wilkins.