Abebe Worku, Mozaffari Mahmood S
Department of Oral Biology and Maxillofacial Pathology School of Dentistry, Medical College of Georgia, Augusta, GA 30912-1128, USA.
J Cardiovasc Pharmacol. 2007 Nov;50(5):590-7. doi: 10.1097/FJC.0b013e318150d104.
The vascular effects of glucose-intolerance were investigated using the neonatal streptozotocin-treated (nSTZ) rat model. Glucose-intolerance was initiated by administration of STZ (90 mg/kg, IP) into 2-day-old male rats. Aortic reactivity was assessed in vitro at 3 and 6 months of age. Both the 3- and 6-month-old nSTZ rats displayed higher blood glucose levels in response to a glucose challenge. At 3 months of age, aortic responsiveness to both norepinephrine and acetylcholine was not altered. However, at 6 months of age, the responses of endothelium-denuded aortas from nSTZ rats to norepinephrine and serotonin were enhanced compared to controls. Endothelium-mediated relaxation of aortas from these animals to acetylcholine was also augmented, and this effect was linked to NO release. Although norepinephrine did not elicit enhancement of aortic contraction in calcium-free medium in 6-month-old nSTZ rats, the responses to both maximum and submaximum concentrations of the agonist after readdition of calcium were greater in these tissues than in control preparations. Pretreatment of aortas with calphostin C eliminated the difference in NE-induced contraction between the control and experimental groups. Although the concentration-response curves for phorbol 12,13-dibutyrate were not different between the 2 groups, the responses of the aortas from 6-month-old nSTZ rats to a submaximum concentration of the phorbol ester were enhanced relative to controls, and this enhancement was normalized with calphostin C. Overall, the data suggest that glucose-intolerance of sufficient duration causes increases in vascular reactivity to agonists. While these findings warrant further investigations, such vascular alterations during the prediabetes stage of glucose intolerance can be a predisposing factor for the eventual development of cardiovascular complications.
使用新生链脲佐菌素处理（nSTZ）大鼠模型研究了葡萄糖不耐受的血管效应。通过向2日龄雄性大鼠腹腔注射链脲佐菌素（90 mg/kg，IP）引发葡萄糖不耐受。在3个月和6个月大时体外评估主动脉反应性。3个月和6个月大的nSTZ大鼠在葡萄糖刺激下均表现出较高的血糖水平。3个月大时，主动脉对去甲肾上腺素和乙酰胆碱的反应性未改变。然而，在6个月大时，与对照组相比，nSTZ大鼠去内皮主动脉对去甲肾上腺素和5-羟色胺的反应增强。这些动物主动脉对乙酰胆碱的内皮介导舒张也增强，且这种效应与一氧化氮释放有关。尽管在6个月大的nSTZ大鼠中，去甲肾上腺素在无钙培养基中未引起主动脉收缩增强，但在重新添加钙后，这些组织对激动剂最大和次最大浓度的反应均大于对照制剂。用钙磷蛋白C预处理主动脉消除了对照组和实验组之间去甲肾上腺素诱导收缩的差异。尽管两组之间佛波醇12,13-二丁酸酯的浓度-反应曲线无差异，但6个月大的nSTZ大鼠主动脉对次最大浓度佛波醇酯的反应相对于对照组增强，且这种增强用钙磷蛋白C可恢复正常。总体而言，数据表明足够长时间的葡萄糖不耐受会导致血管对激动剂的反应性增加。虽然这些发现值得进一步研究，但在葡萄糖不耐受的糖尿病前期阶段的这种血管改变可能是心血管并发症最终发展的一个易感因素。
