Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.
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.
Cheetham
C
C
Department of Human Movement and Exercise Science, The University of Western Australia, Royal Perth Hospital, Australia.
Collis
J
J
O'Driscoll
G
G
Stanton
K
K
Taylor
R
R
Green
D
D
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
D057911:Angiotensin Receptor Antagonists; D019808:Losartan