Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria.
BACKGROUND
Microalbuminuria is associated with dysfunction of the vascular endothelium in patients with diabetes mellitus. The objective of the present study was to determine whether treatment with losartan at a dose sufficient to lower urinary albumin excretion was accompanied by an improvement in endothelial function in type 2 diabetic patients with microalbuminuria.


METHODS
Endothelial function was measured in 80 type 2 diabetic patients with microalbuminuria and 68 non-diabetic controls using high-resolution vascular ultrasound. The diabetic patients were randomised to receive either losartan 50 mg daily or placebo in a 6-month double-blind study. Urinary albumin excretion and endothelial function were assessed at baseline, 3 and 6 months.


RESULTS
Both endothelium-dependent (p<0.01) and -independent vasodilation (p<0.01) were significantly impaired in diabetic patients with or without history of hypertension compared to the non-diabetic controls. At baseline, the losartan- and placebo-treated groups were comparable in their clinical characteristics. Blood pressure did not change significantly in either group throughout the study. Urinary mean albumin excretion rate (MAER) decreased in the losartan-treated group (p<0.01) whereas an increase was observed in the placebo group (p<0.05). At 6 months, the losartan-treated group had significantly lower MAER than the placebo-treated group [54.5 (58.3) vs 78.5 (100.5) microg/min, p<0.05; median (interquartile range)]. No significant differences were found in endothelium-dependent or -independent vasodilation.


CONCLUSIONS
Type 2 diabetic patients with microalbuminuria have impaired endothelium-dependent and -independent vasodilation. Treatment with low-dose losartan is sufficient to reduce microalbuminuria in these patients without alteration in endothelial function and systemic blood pressure.
Tan
Kathryn C B
KC
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. kcbtan@hkucc.hku.hk
Chow
Wing-Sun
WS
Ai
Victor H G
VH
Lam
Karen S L
KS
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy*; D057911:Angiotensin Receptor Antagonists; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D010919:Placebos; D019808:Losartan