Suppression of advanced glycation and lipoxidation end products by angiotensin II type-1 receptor blocker candesartan in type 2 diabetic patients with essential hypertension.
OBJECTIVE
This study investigated whether the angiotensin II type-1 receptor blocker (ARB) candesartan affects markers of oxidative stress in type 2 diabetes mellitus (DM) patients with essential hypertension (EH).


METHODS
Urinary excretion of pyrraline (PR), pentosidine (PT), acrolein (AC), and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and microalbuminuria were assessed in patients with DM complicated by EH who were treated with candesartan 4 mg/day for 3 months.


RESULTS
In a total of 25 patients urinary excretion of PR (nmol/g · cr), PT (pmol/g · cr), and 8-OH-dG (ng/mg · cr) was significantly (all P < 0.05) decreased from (mean ± SEM) 11.9 ± 1.9, 30.6 ± 2.4, and 7.9 ± 0.6, respectively, at baseline to 8.4 ± 1.4, 27.1 ± 2.0, and 6.9 ± 0.6, respectively, at 3 months. Meanwhile, excretion of AC was unaltered from 209.6 ± 40.0 to 189 ± 24.8 nmol/mgcr (P = NS). Urinary albumin excretion was significantly (P < 0.05) reduced from 27.7 ± 4.6 to 14.1 ± 1.1 mg/g · cr. There were weak but statistically significant positive correlations between the change of urinary 8-OH-dG excretion and that of albumin (r = 0.414; P < 0.05) and change of hemoglobin (Hb) A1c (r = 0.45; P < 0.05).


CONCLUSIONS
Candesartan exerts protective effect(s) on the cardiovascular system by suppression of oxidative stress--mainly through inhibiting production of advanced glycation end products (AGEs) rather than of advanced lipoxidation end products (ALEs)--in type 2 DM patients with EH.
Department of Internal Medicine, Ono Yoshiaki Medical Clinic.
Yoshiaki
Y
Ono
Kenji
K
Mizuno
Michihiko
M
Takahashi
Yukio
Y
Miura
Tsuyoshi
T
Watanabe
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D000075222:Essential Hypertension; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017127:Glycation End Products, Advanced; D013777:Tetrazoles; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C081643:candesartan