Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Lipids Health Dis. 2010 May 19;9:51. doi: 10.1186/1476-511X-9-51.
The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57) and hypercholesterolemic (ApoE) female mice in both normal and ovariectomized conditions.
Twenty week-old C57 and ApoE mice underwent ovariectomy or sham surgery and were studied 30 days later. The vascular reactivities to norepinephrine (NE, 10(-9) to 2 x 10(-3) mol/L), acetylcholine (ACh) and sodium nitroprusside (SNP) (10(-10) to 10(-3) mol/L) were evaluated in the isolated mesenteric arteriolar bed through dose-response curves.
ACh-induced relaxation was significantly reduced (P < 0.05) in ApoE compared with C57 animals, as indicated by both the maximal response (37 +/- 4% vs. 72 +/- 1%) and the LogEC50 (-5.67 +/- 0.18 vs. -6.23 +/- 0.09 mol/L). Ovariectomy caused a significant impairment in ACh-induced relaxation in the C57 group (maximal response: 61 +/- 4%) but did not worsen the deficient state of relaxation in ApoE animals (maximal response: 39 +/- 5%). SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice.
These data show an impairment of endothelial function in the resistance vessels of spontaneously atherosclerotic (ApoE-deficient) female mice compared with normal (C57) female mice. The endothelial dysfunction in hypercholesterolemic animals was so marked that ovariectomy, which impaired endothelial function in C57 mice, did not cause additional vascular damage in ApoE-deficient mice.
载脂蛋白 E 缺陷（ApoE）小鼠是自发性动脉粥样硬化的一种鼠模型，其高胆固醇血症对血管舒缩功能的影响仍不清楚。这些研究主要是在喂饲高脂肪饮食的雄性小鼠的导性血管中进行的。在本研究中，我们评估了正常 C57BL/6（C57）和高胆固醇血症（ApoE）雌性小鼠的阻力血管的内皮功能，包括在正常和去卵巢条件下。
20 周龄的 C57 和 ApoE 小鼠接受去卵巢或假手术，并在 30 天后进行研究。通过剂量反应曲线，在分离的肠系膜小动脉床中评估去甲肾上腺素（NE，10(-9) 至 2 x 10(-3) mol/L）、乙酰胆碱（ACh）和硝普钠（SNP）（10(-10) 至 10(-3) mol/L）对血管的反应性。
与 C57 动物相比，ApoE 动物的 ACh 诱导的舒张明显减少（P < 0.05），表现在最大反应（37 +/- 4% vs. 72 +/- 1%）和 LogEC50（-5.67 +/- 0.18 vs. -6.23 +/- 0.09 mol/L）。去卵巢导致 C57 组 ACh 诱导的舒张明显受损（最大反应：61 +/- 4%），但并未使 ApoE 动物的舒张缺陷状态恶化（最大反应：39 +/- 5%）。SNP 诱导的血管舒张和 NE 诱导的血管收缩在 ApoE 和 C57 雌性小鼠中相似。
这些数据表明，与正常（C57）雌性小鼠相比，自发性动脉粥样硬化（ApoE 缺陷）雌性小鼠的阻力血管内皮功能受损。高胆固醇血症动物的内皮功能障碍如此显著，以至于去卵巢导致 C57 小鼠的内皮功能受损，但并未在 ApoE 缺陷小鼠中引起额外的血管损伤。
