This Article Full Text Full Text (PDF) All Versions of this Article: 45/2/264    most recent 01.HYP.0000153305.50128.a1v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Malik, R. A. Articles by Heagerty, A. M. Search for Related Content PubMed PubMed Citation Articles by Malik, R. A. Articles by Heagerty, A. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Diabetes Related Collections Remodeling Type 2 diabetes Clinical Studies Endothelium/vascular type/nitric oxide

(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

This article has been cited by other articles:

				M. Satoh, S. Fujimoto, S. Arakawa, T. Yada, T. Namikoshi, Y. Haruna, H. Horike, T. Sasaki, and N. Kashihara Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3806 - 3813. [Abstract] [Full Text] [PDF]

				J. Su, P. A. Lucchesi, R. A. Gonzalez-Villalobos, D. I. Palen, B. M. Rezk, Y. Suzuki, H. A. Boulares, and K. Matrougui Role of Advanced Glycation End Products With Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic Mice Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1432 - 1438. [Abstract] [Full Text] [PDF]

				S. Belmadani, D. I. Palen, R. A. Gonzalez-Villalobos, H. A. Boulares, and K. Matrougui Elevated Epidermal Growth Factor Receptor Phosphorylation Induces Resistance Artery Dysfunction in Diabetic db/db Mice Diabetes, June 1, 2008; 57(6): 1629 - 1637. [Abstract] [Full Text] [PDF]

				C. Savoia, R. M. Touyz, F. Amiri, and E. L. Schiffrin Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Resistance Artery Stiffness in Hypertensive Patients Hypertension, February 1, 2008; 51(2): 432 - 439. [Abstract] [Full Text] [PDF]

				C. Savoia, R. M. Touyz, and E. L. Schiffrin Response to Are the Eutrophic Effects of Angiotensin Receptor Blockers Real? Hypertension, October 1, 2006; 48(4): E19 - E19. [Full Text] [PDF]

				C. Savoia, R. M. Touyz, D. H. Endemann, Q. Pu, E. A. Ko, C. De Ciuceis, and E. L. Schiffrin Angiotensin Receptor Blocker Added to Previous Antihypertensive Agents on Arteries of Diabetic Hypertensive Patients Hypertension, August 1, 2006; 48(2): 271 - 277. [Abstract] [Full Text] [PDF]

				L. J. Coppey, E. P. Davidson, T. W. Rinehart, J. S. Gellett, C. L. Oltman, D. D. Lund, and M. A. Yorek ACE Inhibitor or Angiotensin II Receptor Antagonist Attenuates Diabetic Neuropathy in Streptozotocin-Induced Diabetic Rats Diabetes, February 1, 2006; 55(2): 341 - 348. [Abstract] [Full Text] [PDF]