A PHARMACOLOGICAL STUDY ON THE DEVELOPMENT OF VASCULAR FUNCTIONAL DISORDER DURING VASCULAR REMODELING

本研究探讨了(1)可能作用于受损血管的海龙类化合物的药理血管活性；(2)改变了这些血管的肾上腺素能神经传递；在前一部分的基础上，研究了15-羟基过氧二十碳四烯酸和感觉神经肽的血管活性特性与内皮功能的关系。结果表明，15-羟基过氧二十碳四烯酸既能引起内皮依赖性的血管松弛，又能引起血管收缩，这与所研究的血管的浓度和来源有关。此外，感觉神经肽作为神经效应器-内皮相互作用的其他主要介质，也表现出不同的血管松弛模式，即内皮一氧化氮介导的或直接的血管松弛，这取决于制备方法、动脉或静脉。此外，本研究还探讨了内皮素对血管肾上腺素能收缩的影响。内皮素通过ET_A受体…增强血管肾上腺素能收缩本研究的后半部分研究了受损肌肉动脉中肾上腺素能收缩(AC)的变化调制。以微球损伤的豚鼠股动脉(FA)为材料。一氧化氮合酶抑制剂显著增加正常和损伤FA的AC，损伤FA的增强程度明显低于对照FA，去甲肾上腺素预收缩后乙酰胆碱的松弛作用也明显减弱。在形态学上，损伤动脉内皮细胞进行性增厚。这些结果表明，减弱一氧化氮对AC的抑制，并伴有内皮细胞增厚，可增加损伤肌动脉的血管张力。为了进一步阐明损伤动脉中神经效应-内皮相互作用改变的机制，研究了血小板激活因子对血管AC的影响，结果表明，该因子通过环氧合酶产生的二十糖类化合物(S)以一种内皮依赖的方式调节AC。促炎症细胞因子的作用也在研究中。较少

This study investigate (1) pharmaco-physiological vasoactive properties of the autacoids possibly acting in injured vessels, and (2) altered adrenergic neurotransmission in these vessels.With respect to the former part, vasoactive properties of 15-hydroperoxyeicosatetraenoic acid and sensory neuropeptides were studied in relation to endothelial function. As a result, 15-hydroperoxyeicosatetraenoic acid induced both endothelium-dependent vasorelaxation and vasoconstriction which were dependent upon the concentration and the source of the studied vessels. Additionally, sensory neuropeptides, other principal mediators of neuroeffector-endothelial interaction, also showed different modes of vasorelaxation, endothelial nitric oxide-mediated or direct vasorelaxation, which were dependent upon the preparations, arteries or veins. Moreover, this study investigated the effects of endothelins on vascular adrenergic contraction. Endothelins augmented vascular adrenergic contraction via ET_A recep … More tors.The latter part of the present study investigated altered modulation of adrenergic contraction (AC) in injured muscular artery. Microballoon-injured guinea pig femoral artery (FA) served as material. Nitric oxide synthetase inhibitor significantly augmented AC in both control and injured FA.The degree of the augmentation was significantly attenuated in injured FA,compared with control FA.And so was acetylcholine-induced relaxation after noradrenaline precontraction. Morphologically, progressive endothelial thickening was observed in injured FA.These results indicate that attenuated inhibition of AC with nitric oxide, accompanied by endothelial thickening, could increase vascular tone in injured muscular artery. To further elucidate the mechanism of altered neuroeffector-endothelial interaction in injured artery, effects of platelet-activating factor on vascular AC was studied and this factor was shown to sugment AC via cyclo-oxygenase-generated eicosanoid (s) in an endothelium-dependent manner. Effects of proinflammatory cytokines are also being studied. Less