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 (t(1/2)). 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), t(1/2) was decreased (11.1 +/- 1.9 vs. 17.2 +/- 2.2 s), and FMD was altered (radial diameter increase 203 +/- 14 vs. 304 +/- 15 microm). Compared with placebo, only D2 decreased MAP (placebo 115 +/- 3; D1 112 +/- 4; D2 103 +/- 4 mm Hg) and increased t(1/2) (placebo 11.1 +/- 1.9; D1 8.7 +/- 1.5; D213.0 +/- 1.9 s). Conversely, D1 and D2 increased FMD (placebo 203 +/- 14; D1 218 +/- 22; D2 227 +/- 23 microm) 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.