title: Divergent effects of angiotensin-converting enzyme inhibition on blood pressure and endothelial function in obese humans.
abstract: Endothelial dysfunction is a pivotal early event in the development of atherosclerosis and a characteristic feature of obesity. This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on endothelial function in people who were obese but otherwise healthy. We performed a double-blind, randomised, placebo-controlled study examining the effect of the ACE inhibitor perindopril (4 mg per day) on flow-mediated vasodilatation (FMD) of the brachial artery, arterial blood pressure, glucose homeostasis and inflammatory cytokines. Eighteen obese subjects (all body mass index > 30 kg/m2) were randomised to receive perindopril or placebo for four weeks. Perindopril led to a fall in systolic blood pressure from 131 (standard error of mean [SEM] 3) to 117(5) mmHg and diastolic blood pressure from 74(4) mmHg to 68(4) mmHg, both p<0.001. Despite this fall in blood pressure, ACE inhibition had no effect on FMD, 8.2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD.
authors.affiliation: GKT School of Medicine, King's College, London, SE5 9PJ, UK.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Williams
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Chowienczyk
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wheatcroft
authors.forename: Ameet G
authors.initials: AG
authors.lastname: Patel
authors.forename: Roy A
authors.initials: RA
authors.lastname: Sherwood
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kearney
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001916:Brachial Artery / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D020913:Perindopril / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril