Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus.
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.
Malik
Rayaz A
RA
Cardiovascular Research Group, Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
Schofield
Ian J
IJ
Izzard
Ashley
A
Austin
Clare
C
Bermann
Georgina
G
Heagerty
Anthony M
AM
D000109:Acetylcholine; D000328:Adult; D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside; D013777:Tetrazoles / Q000627:therapeutic use*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D000109:Acetylcholine; C077793:candesartan cilexetil