Fixed combination of perindopril and indapamide at low dose improves endothelial function in essential hypertensive patients after acute administration

Abstract

Background: Fixed combination of angiotensin-converting enzyme inhibitors (ACEIs) with thiazide-type diuretics at low dose has been used as first-line therapy for the treatment of essential hypertension but their effect on conduit artery endothelial dysfunction remains unknown. Methods: Thirteen hypertensive patients were assessed after acute administration of a placebo, fixed combination of perindopril-indapamide at low dose: D1 (2 mg/0.625 mg)and twice this dose: D2 (4 mg/1.25 mg), during a double-blind, randomized, crossover study, and were compared with 13 matched controls. Mean arterial pressure (MAP), radial artery diameter (echotracking) and flow (Doppler) were measured during flow-mediated dilatation (FMD) induced by post-ischemic hyperemia (PIH). PIH was characterized by peak flow and duration of hyperemia (t1/2). Endothelium-independent dilatation was assessed by trinitrine. Results: In hypertensive patients compared with controls, basal radial artery diameter and flow, peak flow, and trinitrine responses were similar while MAP was increased (115 ± 3 vs. 87 ± 2 mm Hg), t1/2 was decreased (11.1 ± 1.9 vs. 17.2 ± 2.2 s), and FMD was altered (radial diameter increase: 203 ± 14 vs. 304 ± 15 μm). Compared with placebo, only D2 decreased MAP (placebo: 115 ± 3; D1: 112 ± 4; D2: 103 ± 4 mm Hg) and increased t1/2 (placebo: 11.1 ± 1.9; D1: 8.7 ± 1.5; D2:13.0 ± 1.9 s). Conversely, D1 and D2 increased FMD (placebo: 203 ± 14; D1: 218 ± 22; D2: 227 ± 23 μm) with no change in basal diameter and flow, peak flow, and trinitrine responses. Conclusion: These results demonstrate that a fixed combination of ACEI/diuretic at low dose significantly improves radial artery FMD in hypertensive patients and suggest a direct effect on conduit artery endothelium that may contribute to vascular protection. © 2008 American Journal of Hypertension, Ltd.