title: Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus.
abstract: The renin-angiotensin system plays an important role in the elevation of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in hypertensive patients, so the present study was designed to examine whether angiotensin-converting enzyme (ACE) activity is also involved in the mechanism of ADMA elevation in type 2 diabetes mellitus (NIDDM). A crossover study was performed to determine if ACE inhibition with perindopril (4 mg/day) for 4 weeks decreases serum ADMA concentration and plasma von Willebrand factor (vWF) level (a marker of endothelial injury) in 11 patients with NIDDM. None of the patients was treated with insulin or oral hypoglycemic drugs, and none had major diabetic complications. Before the protocol began, serum ADMA and plasma vWF were significantly higher in the 11 NIDDM patients, when compared with 8 control subjects without diabetes. Perindopril did not affect blood pressure or glucose metabolism, but did significantly decrease serum ADMA and plasma vWF. These results suggest that endothelial injury associated with ADMA elevation may be present even in patients with non-complicated NIDDM, and that increased activity of ACE may be involved in such endothelial dysfunction.
authors.affiliation: Department of Cardiovascular Medicine, Yamaguchi Red Cross Hospital, Japan. iakira@mbc.sphere.ne.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Takahiro
authors.initials: T
authors.lastname: Narishige
authors.forename: Kouhei
authors.initials: K
authors.lastname: Muramatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D007118:Immunoassay; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D020913:Perindopril / Q000494:pharmacology* / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000502:physiology; D014841:von Willebrand Factor / Q000032:analysis* / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014841:von Willebrand Factor; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril