Ono Hiroyoshi, Minatoguchi Shinya, Watanabe Kazuhiro, Yamada Yoshihisa, Mizukusa Takahisa, Kawasaki Hironobu, Takahashi Hidemi, Uno Takashi, Tsukamoto Tatsuo, Hiei Kunihiko, Fujiwara Hisayoshi
Ibi Kosei Hospital, Gifu, Japan.
Hypertens Res. 2008 Feb;31(2):271-9. doi: 10.1291/hypres.31.271.
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.
在动物研究中,已报道坎地沙坦可产生一氧化氮(NO)并降低氧化应激。我们研究了坎地沙坦对高血压患者NO生成、氧化应激以及颈动脉内膜中层厚度(IMT)的影响。100名年龄匹配的高血压患者被纳入血管紧张素II受体阻滞剂(ARB)组(n = 50)或非ARB组(n = 50)。ARB组接受8 mg坎地沙坦治疗,必要时联合使用钙通道阻滞剂、血管紧张素转换酶(ACE)抑制剂和/或β受体阻滞剂。非ARB组接受ARB以外的药物治疗。治疗前以及治疗后12个月和24个月通过超声心动图评估颈动脉IMT。测量氧化应激指标8-羟基-2'-脱氧鸟苷(8-OHdG)的尿水平以及NO指标NOx的血清水平。两组血压均降至140/90 mmHg以下,降幅相同。治疗后12个月和24个月,ARB组颈动脉IMT显著降低,而非ARB组未降低。ARB组治疗后6个月和12个月8-OHdG尿水平显著降低,而非ARB组未降低。ARB组治疗后6个月和12个月NOx血清水平显著升高,而非ARB组未升高。总之,坎地沙坦通过增强高血压患者的NO生成和降低氧化应激来降低颈动脉IMT。