Effect of long-term angiotensin-converting enzyme inhibition on endothelial function in patients with the insulin-resistance syndrome.
Cardiovascular risk factors such as hypertension, diabetes, and dyslipemia are associated with an impaired endothelium-dependent vasodilation. In patients with type 2 diabetes mellitus, these risk factors are frequently clustered. We investigated whether long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril can improve endothelium-dependent vasodilation in this particular group of patients. We selected 10 patients with type 2 diabetes and hypertension (age 59.4 +/- 3.2 years, body mass-index 29.7 +/- 1.5 kg.m-2, blood pressure 169 +/- 6/92 +/- 1 mm Hg, total cholesterol 6.6 +/- 0.3 mM). Using venous occlusion plethysmography, we recorded the increases in forearm blood flow (FBF) in response to three vasodilator stimuli: (a) 5 min of forearm ischemia, (b) infusion of the endothelium-dependent vasodilator methacholine (Mch) into the brachial artery (0.03, 0.3, and 1.0 micrograms/min/100 ml), and (c) intraarterial infusion of the endothelium-independent vasodilator sodium nitroprusside (SNP 0.06, 0.2, 0.6 microgram/min/100 ml). This procedure was repeated after 6 months of treatment with perindopril 4-8 mg/day. Forearm vascular resistance (FVR) was calculated by the quotient of the mean arterial pressure (MAP) and the FBF. Perindopril reduced blood pressure (BP) by 19/10 mm Hg (p < 0.05) and increased baseline FVR, but improved neither the maximal percentage decrease in vascular resistance induced by Mch (from -80 +/- 2 to -82 +/- 2%) nor that induced by SNP (from -73 +/- 3 to -72 +/- 3%). Perindopril decreased the FVR reached after the ischemic stimulus from 6.5 +/- 1.2 to 4.8 +/- 0.6 U (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Bijlstra
P J
PJ
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Smits
P
P
Lutterman
J A
JA
Thien
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005542:Forearm / Q000033:anatomy & histology / Q000098:blood supply; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D020913:Perindopril; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D016210:Methacholine Chloride; D009599:Nitroprusside; D020913:Perindopril