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Background-Increased pulse pressure, an indicator of conduit vessel stiffness, is a strong independent predictor of cardiovascular events in hypertensive cohorts, which suggests that reduction of conduit vessel stiffness may be desirable in hypertension. Methods and Results-We assessed changes in pulse pressure and conduit vessel stiffness in a 12-week double-blind, randomized clinical trial that compared monotherapy with the ACE inhibitor enalapril 40 mg daily (nϭ87) versus the vasopeptidase (dual ACE and neutral endopeptidase) inhibitor omapatrilat 80 mg daily (nϭ80) in patients with systolic hypertension. Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be Ն160 mm Hg. With the use of calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed before randomization and at 12 weeks. Characteristic impedance (Z c ), a direct measure of the stiffness of the central aorta, was calculated from the ratio of changes in carotid pressure and aortic flow in early systole. Omapatrilat compared with enalapril produced greater reductions in peripheral (Ϫ8.2Ϯ12.2 versus Ϫ4.0Ϯ12.2 mm Hg, PϽ0.05) and central (Ϫ10.2Ϯ16.2 versus Ϫ3.2Ϯ16.9 mm Hg, PϽ0.01) pulse pressures and Z c (237Ϯ83 to 208Ϯ70 versus 225Ϯ87 to 231Ϯ94 dyne · s/cm 5 , PϽ0.001); the latter remained significant (PϽ0.05) after adjusting for change in mean pressure. Conclusions-Greater reductions in pulse pressure and Z c in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms and underscore a potential role for pharmacological modulation of natriuretic peptides in the treatment of hypertension.

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