title: Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.
abstract: OBJECTIVE
  The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM).
  
  
  BACKGROUND
  Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function.
  
  
  METHODS
  The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography.
  
  
  RESULTS
  Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed.
  
  
  CONCLUSIONS
  Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.
authors.affiliation: Department of Human Movement and Exercise Science, The University of Western Australia, Royal Perth Hospital, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Cheetham
authors.forename: J
authors.initials: J
authors.lastname: Collis
authors.forename: G
authors.initials: G
authors.lastname: O'Driscoll
authors.forename: K
authors.initials: K
authors.lastname: Stanton
authors.forename: R
authors.initials: R
authors.lastname: Taylor
authors.forename: D
authors.initials: D
authors.lastname: Green
mesh_terms: D057911:Angiotensin Receptor Antagonists; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004311:Double-Blind Method; D004727:Endothelium / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D019808:Losartan