Alnaeb M E, Thompson C S, Seifalian A M, Hamilton G, Mikhailidis D P
Vascular Unit, Royal Free Hampstead NHS Trust Hospital, London, UK.
In Vivo. 2007 Nov-Dec;21(6):1069-74.
Atherosclerosis can influence the expression of endothelial nitric oxide synthase (eNOS) as well as endothelin-1 (ET-1) and 5-hydroxytryptamine (5HT; serotonin) receptors. Diabetes has an effect on the onset, severity and pattern of atherosclerosis with a predilection for more distal arteries. We aimed to identify regional differences in the distribution of eNOS activity, ET-1 and 5HT receptors in vascular tissues obtained from control and diabetic rabbits.
The mid abdominal aorta, right renal and right femoral arteries were harvested from 12 adult rabbits (6 months old, 3-3.9 kg); 8 controls and 4 diabetic (induced using alloxan 7 months previously). Samples were stored in liquid nitrogen for Western immunoblotting for eNOS as well as ET-1 and 5HT receptors.
Significant differences were found in the distribution of eNOS, ET-1 and 5HT between the aorta, renal and femoral arteries in the controls. The number of ET-1 receptors was significantly higher (aorta; p=0.016, renal; p=0.004, femoral; p=0.05,) whereas, the expression of eNOS was significantly lower (aorta; p =0.004, renal; p =0.004, femoral; p =0.008) when comparing arteries from normal rabbits with these from diabetics ones. The number of 5HT receptors was higher in arteries from diabetic rabbits but this was not statistically significantly.
The "regional" distribution of eNOS activity as well as ET-1 and 5HT receptors in control rabbits varies significantly according to the vessel assessed. Further studies are needed to evaluate the effect of blocking these receptors (e.g. on the risk of re-stenosis). Regional receptor differences may explain why diabetes is linked with a predilection for atherosclerosis (and possibly calcification) in distal arteries.
动脉粥样硬化会影响内皮型一氧化氮合酶(eNOS)以及内皮素 -1(ET-1)和5-羟色胺(5HT;血清素)受体的表达。糖尿病会对动脉粥样硬化的发病、严重程度和模式产生影响,且更易累及远端动脉。我们旨在确定从对照兔和糖尿病兔获取的血管组织中eNOS活性、ET-1和5HT受体分布的区域差异。
从12只成年兔(6月龄,3 - 3.9千克)获取腹主动脉中段、右肾动脉和右股动脉;8只为对照兔,4只为糖尿病兔(7个月前用四氧嘧啶诱导产生糖尿病)。样本储存于液氮中,用于对eNOS以及ET-1和5HT受体进行蛋白质免疫印迹分析。
在对照兔中,主动脉、肾动脉和股动脉之间的eNOS、ET-1和5HT分布存在显著差异。与正常兔的动脉相比,糖尿病兔动脉中ET-1受体数量显著更高(主动脉;p = 0.016,肾动脉;p = 0.004,股动脉;p = 0.05),而eNOS的表达显著更低(主动脉;p = 0.004,肾动脉;p = 0.004,股动脉;p = 0.008)。糖尿病兔动脉中5HT受体数量更高,但无统计学意义。
对照兔中eNOS活性以及ET-1和5HT受体的“区域”分布根据所评估的血管不同而有显著差异。需要进一步研究来评估阻断这些受体的作用(例如对再狭窄风险的影响)。区域受体差异可能解释了为什么糖尿病与远端动脉更易发生动脉粥样硬化(以及可能的钙化)有关。