The influence of perindopril and the diuretic combination amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients.
OBJECTIVE
To compare the cardiovascular effects of 6 months of treatment with the angiotensin converting enzyme inhibitor perindopril and with the diuretic combination amiloride+hydrochlorothiazide, and to study possible persistence of observed treatment effects after discontinuation of antihypertensive therapy.


METHODS
A placebo run-in period preceded a 6-month active-treatment phase in 41 patients with essential hypertension, according to a double-blind, randomized, parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3-month single-blind placebo run-out period.


RESULTS
After 6 months of treatment, systolic blood pressure was reduced significantly by perindopril (supine by 11%, sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by 12%). Diastolic blood pressure was also decreased significantly by perindopril (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by 4%, sitting by 9%). Mean arterial pressure decreased significantly during treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by 6%). Cardiac index increased with perindopril (by 6%), because of an increased stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac function. Systemic vascular resistance index decreased significantly more with perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The distensibility of the common carotid artery was significantly enhanced by perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1% difference). The difference between perindopril and amiloride+hydrochlorothiazide for carotid distensibility was statistically significant. The compliance of the common carotid artery tended to be increased more by perindopril (by 7%) than by amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance. After withdrawal of therapy, for both drugs, all treatment-induced changes were reversed to pretreatment values within 7 weeks.


CONCLUSIONS
The distensibility of the elastic common carotid artery was increased by perindopril, but not by amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries and systemic vascular resistance improved with both drugs, but in general the changes were more pronounced with perindopril than with amiloride+hydrochlorothiazide. The present results indicate a more pronounced effect of perindopril at both macro- and microcirculatory levels, which will consequently lead to a larger decrease in cardiac afterload. After discontinuation of therapy all parameters returned to baseline values within 7 weeks.
Kool
M J
MJ
Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
Lustermans
F A
FA
Breed
J G
JG
Struyker Boudier
H A
HA
Hoeks
A P
AP
Reneman
R S
RS
Van Bortel
L M
LM
D000328:Adult; D000584:Amiloride / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects*; D001794:Blood Pressure; D003187:Compliance; D004232:Diuretics; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006321:Heart / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020913:Perindopril; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004338:Drug Combinations; D007211:Indoles; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D000584:Amiloride; D020913:Perindopril