LOW-LEVEL HYPERLIPIDEMIA IMPAIRS ENDOTHELIUM-DEPENDENT RELAXATION OF PORCINE CORONARY-ARTERIES BY 2 MECHANISMS - FUNCTIONAL CHANGE IN ENDOTHELIUM AND IMPAIRMENT OF ENDOTHELIUM-DEPENDENT RELAXATION BY 2 MEDIATORS
LOW-LEVEL HYPERLIPIDEMIA IMPAIRS ENDOTHELIUM-DEPENDENT RELAXATION OF PORCINE CORONARY-ARTERIES BY 2 MECHANISMS - FUNCTIONAL CHANGE IN ENDOTHELIUM AND IMPAIRMENT OF ENDOTHELIUM-DEPENDENT RELAXATION BY 2 MEDIATORS
复制标题
DOI：
10.1016/0021-9150(91)90229-v
复制
发表时间：
1991-03-01
期刊：
影响因子：
5.3
通讯作者：
KUZUYA, F
中科院分区：
文献类型：
--
作者：
HAYASHI, T;ISHIKAWA, T;KUZUYA, F
我们评估了低水平高脂血症和体外暴露于致动脉粥样硬化脂蛋白（LDL， VLDL）对离体猪冠状动脉血管反应性的影响。首先，我们研究了饲喂4周和9周高胆固醇饲粮对猪血管反应性的影响（C4和C9猪）。饲喂高胆固醇饲料的猪血清胆固醇水平达到218.5 +/- 32.9 mg/dl，而对照组为85.5 +/- 8.4 mg/dl。检查左冠状动脉降支段。高胆固醇血症没有显著改变KCl或前列腺素f2 - α诱导的收缩，Ca2+离子离子、A23187或硝酸甘油诱导的松弛也没有显著改变。与正常动物相比，C4猪体内高而非低浓度缓激肽诱发的内皮依赖性松弛（EDR）减少。缓激肽、P物质和血清素诱发的edr在C9猪中显著降低。组织学上，通过光镜和电镜观察，C4猪冠状动脉未见脂肪改变或内膜增厚。仅在C9猪的部分动脉中观察到微小的变化（内膜增厚和内部弹性板碎裂）。其次，研究了LDL和VLDL对血管反应性的直接影响。低密度脂蛋白预孵育可以抑制正常猪和高胆固醇猪冠状动脉中由缓激肽和A23187引起的EDR，但在C4和C9猪中，LDL预孵育可以抑制由P物质或血清素引起的动脉舒张，而在对照动物中则没有。抑制程度在C9猪中尤为明显。VLDL对EDR的抑制作用弱于LDL。吲哚美辛（5-mu-M）没有改变脂蛋白的抑制作用。LDL和VLDL对硝酸甘油诱导的血管舒张均无影响。这些结果与内皮依赖性动脉舒张甚至在胆固醇诱导的动脉粥样硬化的早期阶段减弱的观点一致。致动脉粥样硬化脂蛋白可能通过两种因素进一步损害高脂血症猪动脉中已降低的EDR，一种是缓激肽和钙离子载体A23187刺激释放的，另一种是P物质和血清素刺激释放的。
We evaluated the effect of a low level of hyperlipidemia and the effects of in vitro exposure to atherogenic lipoproteins (LDL, VLDL) on the vascular responsiveness of isolated porcine coronary arteries. Firstly we studied the change in vascular responsiveness induced by feeding a cholesterol-rich diet to pigs for 4 and 9 weeks (C4 and C9 pigs). The serum cholesterol level in pigs fed a cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in the controls. Segments of the left descending coronary artery were examined. The contraction induced by KCl or prostaglandin F2-alpha was not altered significantly by hypercholesterolemia nor was the relaxation induced by the Ca2+ ionophore, A23187, or by nitroglycerin. Endothelium-dependent relaxation (EDR) evoked by high, but not low, concentrations of bradykinin was reduced in the C4 pigs as compared with those in normal animals. EDRs evoked by bradykinin, substance P, and serotonin were significantly reduced in C9 pigs. Histologically, as observed by light and electron microscopy, fatty changes or intimal thickenings were not seen in the coronary arteries of the C4 pigs. Minimal changes (intimal thickenings and fragmentation of internal elastic lamina) were observed only in parts of arteries of the C9 pigs. Secondly, the direct effects of LDL and VLDL on vascular responsiveness were studied. Although preincubation with LDL inhibited the EDR caused by exposure to bradykinin and A23187 in the coronary arteries of normal and cholesterol-fed pigs, preincubation with LDL inhibited the arterial relaxation induced by exposure to substance P or serotonin in both the C4 and the C9 pigs, but not in the control animals. The degree of inhibition was especially marked in the C9 pigs. The inhibitory effect of VLDL on EDR was weaker than that of LDL. Indomethacin (5-mu-M) did not alter this inhibitory effect of lipoproteins. Neither LDL nor VLDL had any effect on the vascular relaxation induced by nitroglycerin. These results are consistent with the idea that endothelium-dependent arterial relaxation is attenuated even at the very early stage of cholesterol-induced atherosclerosis. Atherogenic lipoproteins may further impair the decreased EDR in the arteries of hyperlipidemic pigs by two factors: one released on stimulation with bradykinin and the calcium ionophore A23187, the other released on stimulation with substance P and serotonin.