2型糖尿病患者脑循环中对全身一氧化氮合酶抑制的反应减弱。

Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes.

作者信息

Nazir F S, Alem M, Small M, Connell J M C, Lees K R, Walters M R, Cleland S J

机构信息

Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

出版信息

Diabet Med. 2006 Apr;23(4):398-402. doi: 10.1111/j.1464-5491.2006.01815.x.

DOI:10.1111/j.1464-5491.2006.01815.x

PMID:16620268

Abstract

AIMS

Diabetes is a major risk factor for stroke, but the mechanisms that impart the excess risk are unclear. Endothelial dysfunction, which has been demonstrated in the coronary and peripheral vasculature of diabetic patients, is an important early marker of vascular disease. However, the effect of diabetes on cerebrovascular endothelium has not been examined. We sought to investigate the effect of diabetes on basal cerebrovascular endothelial function as assessed by response to the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA).

METHODS

Fourteen men with Type 2 diabetes and 15 age-matched male control subjects were recruited. The participants had no clinically evident vascular disease and were taking no vasoactive or lipid-lowering medication. Each received a single 15-min intravenous infusion of L-NMMA (0.8 mol/kg/min). Cerebral blood flow was assessed by colour Doppler imaging of the internal carotid artery (ICA) at 10-min intervals for 20 min prior to and following the infusion. Middle cerebral artery velocity (MCAv) was assessed by transtemporal Doppler ultrasound at the same time points.

RESULTS

L-NMMA produced a mean reduction in ICA flow area under curve (AUC) in the control group of 12.8 +/- 17.8% compared with a 2.1 +/- 21.7% reduction in the group with diabetes (P < 0.05), indicating blunted basal cerebrovascular response to NOS inhibition in the diabetic group. There was no significant change in MCAv following L-NMMA in either group. Mean +/- sd MAP rose 6.4 +/- 4.2 mmHg in the control group vs. 8.8 +/- 3.5 mmHg in the diabetic group [P = not significant (NS)]. No adverse event or symptom was reported.

CONCLUSIONS

Response to NOS inhibition is impaired in the cerebral circulation of patients with diabetes. This observation is consistent with the elevated cerebrovascular risk reported in this population, and may represent a future therapeutic target in stroke prevention.

摘要

目的

糖尿病是中风的主要危险因素，但导致额外风险的机制尚不清楚。内皮功能障碍已在糖尿病患者的冠状动脉和外周血管中得到证实，是血管疾病的重要早期标志物。然而，糖尿病对脑血管内皮的影响尚未得到研究。我们试图通过对一氧化氮合酶（NOS）抑制剂NG-单甲基-L-精氨酸（L-NMMA）的反应来研究糖尿病对基础脑血管内皮功能的影响。

方法

招募了14名2型糖尿病男性患者和15名年龄匹配的男性对照受试者。参与者无临床明显的血管疾病，且未服用血管活性或降脂药物。每人接受一次15分钟的L-NMMA静脉输注（0.8 μmol/kg/min）。在输注前和输注后20分钟内，每隔10分钟通过彩色多普勒成像评估颈内动脉（ICA）的脑血流量。同时通过颞部多普勒超声评估大脑中动脉速度（MCAv）。

结果

与糖尿病组2.1±21.7%的降低相比，对照组L-NMMA使ICA血流曲线下面积（AUC）平均降低12.8±17.8%（P<0.05），表明糖尿病组基础脑血管对NOS抑制的反应减弱。两组L-NMMA输注后MCAv均无显著变化。对照组平均动脉压（MAP）升高6.4±4.2 mmHg，糖尿病组升高8.8±3.5 mmHg[P=无显著性差异（NS）]。未报告不良事件或症状。