Angiotensin converting enzyme inhibition and arterial endothelial function in adults with Type 1 diabetes mellitus.
OBJECTIVE
Arterial endothelial dysfunction is a key early event in atherogenesis, and occurs in asymptomatic adults with Type 1 diabetes mellitus (DM). As angiotensin converting enzyme (ACE) inhibitors have been reported to reverse microvascular endothelial dysfunction acutely, we assessed the longer term effect of ACE inhibition on large vessel endothelial physiology in a randomized, crossover double-blind controlled clinical trial.


METHODS
Flow-mediated arterial dilatation (FMD), which is largely due to endothelial release of nitric oxide, was assessed by vascular ultrasound in 20 Type 1 DM subjects with known endothelial dysfunction. These subjects, aged 28+/-5 years, were studied before and after 12 weeks oral therapy with either the ACE inhibitor perindopril 4 mg daily or the diuretic hydrene (triamterene 50 mg with hydrochlorothiazide 25 mg) daily.


RESULTS
Although perindopril lowered both systolic and diastolic blood pressure by 2.7/3.2 mmHg, respectively (F3,78 = 4.7, P= 0.006; F3,78 = 3.2, P = 0.03), there was no significant effect of either perindopril or hydrene on FMD (baseline FMD before perindopril 4.6+/-2.5%, after 4.1+/-3.4%, baseline FMD before hydrene 5.4+/-3.6%, after 6.0+/-3.3%; F3,78= 1.9, P=0.1). Glycaemic control deteriorated slightly on hydrene whilst lipid levels, heart rate, resting blood flow and the arterial responses to nitroglycerine, a smooth muscle dilator, were unaffected by the treatment given.


CONCLUSIONS
ACE inhibitor therapy for 3 months did not improve arterial endothelial function in Type 1 DM subjects.
McFarlane
R
R
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
McCredie
R J
RJ
Bonney
M A
MA
Molyneaux
L
L
Zilkens
R
R
Celermajer
D S
DS
Yue
D K
DK
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D020913:Perindopril; D014223:Triamterene / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D007211:Indoles; C119097:hydrene; D006852:Hydrochlorothiazide; D014223:Triamterene; D020913:Perindopril