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Hypertension. 2005;45:264-269
Published online before print January 3, 2005, doi: 10.1161/01.HYP.0000153305.50128.a1
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(Hypertension. 2005;45:264.)
© 2005 American Heart Association, Inc.

Scientific Contributions

Effects of Angiotensin Type-1 Receptor Antagonism on Small Artery Function in Patients With Type 2 Diabetes Mellitus

Rayaz A. Malik; Ian J. Schofield; Ashley Izzard; Clare Austin; Georgina Bermann; Anthony M. Heagerty

From the Cardiovascular Research Group (R.A.M., I.J.S., A.I., C.A., A.M.H.), Department of Medicine, Manchester Royal Infirmary, United Kingdom; AstraZeneca R&D (G.B.), Mölndal, Sweden.

Correspondence to A.M. Heagerty, Cardiovascular Research Group, Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. E-mail tony.heagerty{at}man.ac.uk

Endothelial dysfunction has been demonstrated to occur in small arteries from patients with type 2 diabetes and hypertension. The effects of angiotensin II receptor blockade on vessel function were examined using pressure myography in a randomized 12-week double-blind placebo-controlled parallel group study using candesartan cilexitil. The maximal vascular response to acetylcholine (Ach) was impaired at baseline and improved with candesartan. This improvement was primarily caused by an effect in the nitric oxide component of Ach-mediated dilatation. The degree of endothelial dysfunction directly correlated with serum low-density lipoprotein cholesterol levels. Sodium nitroprusside-induced endothelium-independent dilatation was reduced in diabetic patients and intervention with candesartan lead to an improvement in EC50 with no change in maximal response. Vasoconstriction to norepinephrine was normal and did not change with intervention, but responses to angiotensin II were reduced after candesartan in diabetic patients. These results demonstrate that even brief treatment with angiotensin II receptor blockade is associated with a significant improvement in resistance vessel endothelial function.


Key Words: angiotensin II • clinical trials • diabetes mellitus • endothelium • nitric oxide • arterioles




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