Candesartan decreases carotid intima-media thickness by enhancing nitric oxide and decreasing oxidative stress in patients with hypertension.
Candesartan has been reported to produce nitric oxide (NO) and to decrease oxidative stress in animal studies. We investigated candesartan's effect on the production of NO and oxidative stress as well as on carotid intima-media thickness (IMT) in hypertensive patients. One-hundred age-matched hypertensive patients were enrolled into an angiotensin II receptor blocker (ARB) group (n=50) or a non-ARB group (n=50). The ARB group was treated with candesartan 8 mg and, when needed, Ca channel blockers, angiotesin-converting enzyme (ACE) inhibitors, and/or beta-blockers. The non-ARB group was treated with drugs other than ARB. Carotid IMT was assessed by echocardiography before and 12 and 24 months after treatment. The urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an indicator of oxidative stress, and the serum levels of NOx, an indicator of NO, were measured. Blood pressure decreased to below 140/90 mmHg to the same extent in both groups. Carotid IMT decreased significantly in the ARB group, but not in the non-ARB group, at 12 and 24 months after treatment. The urine levels of 8-OHdG decreased significantly at 6 and 12 months after treatment in the ARB group but did not decrease in the non-ARB group. The serum levels of NOx increased significantly at 6 and 12 months after treatment in the ARB group but not in the non-ARB group. In conclusion, candesartan decreases carotid IMT by enhancing NO production and decreasing oxidative stress in patients with hypertension.
Ono
Hiroyoshi
H
Ibi Kosei Hospital, Gifu, Japan.
Minatoguchi
Shinya
S
Watanabe
Kazuhiro
K
Yamada
Yoshihisa
Y
Mizukusa
Takahisa
T
Kawasaki
Hironobu
H
Takahashi
Hidemi
H
Uno
Takashi
T
Tsukamoto
Tatsuo
T
Hiei
Kunihiko
K
Fujiwara
Hisayoshi
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects* / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C081643:candesartan