Fixed combination of perindopril and indapamide at low dose improves endothelial function in essential hypertensive patients after acute administration.
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; D2:13.0 +/- 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.


CONCLUSIONS
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.
Joannides
Robinson
R
Department of Pharmacology, Rouen University Hospital & INSERM U644 (IFRMP 23), Institute for Biomedical Research, University of Rouen, Rouen Cedex, France. robinson.joannides@chu-rouen.fr
Bellien
Jeremy
J
Thurlure
Celine
C
Iacob
Michele
M
Abeel
Murielle
M
Thuillez
Christian
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001775:Blood Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007190:Indapamide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D020913:Perindopril / Q000008:administration & dosage*; D017534:Radial Artery / Q000033:anatomy & histology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D007190:Indapamide; D005996:Nitroglycerin; D020913:Perindopril