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CLINICAL STUDY

Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes

Craig Cheetham, BSc^a, Julie Collis, BSc^a, Gerard O’Driscoll, MB, BCh, BAO, FRACP^b, Kim Stanton, MB, BS, FRACP^||, Roger Taylor, MB, BS, FRACP^b,e and Daniel Green, PhD^a,b

^a Department of Human Movement and Exercise Science,The University of Western Australia, Perth, Australia
^e Department of Medicine, The University of Western Australia, Perth, Australia
^b Department of Cardiology, Royal Perth Hospital and West Australian Heart Research Institute, Perth, Australia; Department of Cardiology
Cardiac Transplant Unit, Royal Perth Hospital and West Australian Heart Research Institute, Perth, Australia
^|| Endocrinology and Diabetic Unit, Royal Perth Hospital and West Australian Heart Research Institute, Perth, Australia

Manuscript received October 21, 1999; revised manuscript received April 11, 2000, accepted June 15, 2000.

Reprint requests and correspondence: Professor R.R. Taylor, Department of Cardiology, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia
heletoey{at}rph.health.wa.gov.au

OBJECTIVES

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.

Abbreviations and Acronyms   ACE = angiotensin converting enzyme   ACh = acetylcholine   FBF = forearm blood flow   FMD = flow mediated dilation   FVR = forearm vascular resistance   LDL = low density lipoprotein   LNMMA = NG-monomethyl-L-arginine   NIDDM = noninsulin-dependent diabetes mellitus   NO = nitric oxide   SNP = sodium nitroprusside

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