Author + information
- Received October 21, 1999
- Revision received April 11, 2000
- Accepted June 15, 2000
- Published online November 1, 2000.
- Craig Cheetham, BSca,
- Julie Collis, BSca,
- Gerard O’Driscoll, MB, BCh, BAO, FRACPb,§,
- Kim Stanton, MB, BS, FRACP∥,
- Roger Taylor, MB, BS, FRACPb,e,* ( and )
- Daniel Green, PhDa,b,§
- ↵*Reprint requests and correspondence: Professor R.R. Taylor, Department of Cardiology, Royal Perth Hospital, Box X2213, GPO, Perth 6847, Western Australia
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).
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.
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.
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.
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.
☆ This study was supported by the Arnold Yeldham and Mary Raine Medical Research Foundation.
- Received October 21, 1999.
- Revision received April 11, 2000.
- Accepted June 15, 2000.
- American College of Cardiology