A PHARMACOLOGICAL STUDY ON THE INTERACTIONS BETWEEN VASOACTIVE AUTACOIDS INVOLVING ENDOTHELIAN CELLS

本研究试图利用血管周围神经刺激(PNS)分离血管组织，探讨基于神经效应器-内皮相互作用的血管平滑肌张力的调节机制。结果提示，三叉神经节上可能存在一氧化氮(NO)释放，参与调节豚鼠动脉(肺动脉和髂动脉)的自主肾上腺素能神经传递。在豚鼠肺动脉，PNS上释放的感觉神经肽(降钙素基因相关肽和P物质)也参与了自主肾上腺素能神经传递的调节。进一步研究了PNS诱导NO释放的机制，表明PNS上释放的去甲肾上腺素可作用于内皮细胞，导致NO的释放。此外，在豚鼠的肺动脉中还发现了一条扩张神经，可释放NO。关于内皮素(ET)-1的作用方式，进行了体内研究。因此，环氧合酶产生的二十烷类化合物(S)的二次释放，主要是血栓素A_2，被认为是ET-1的升压反应的主要原因。用培养的内皮细胞观察ET-1与其他血管活性物质的相互作用，并观察到给予ET-1后培养上清液中前列环素(6-酮-前列腺素F_1α)水平的增加。其他海龙类之间的相互作用正在调查中。

The present study attempted to examine the regulatory mechanism of vascular smooth muscular tone based on neuroeffector-endothelial interaction, employing isolated vascular tissue with the use of perivascular nerve stimulation (PNS). As a result, it is indicated that nitric oxide (NO)might be released on PNS and modulate autonomic adrenergic neurotransmision in guinea pig arteries (pulmonary and iliac artery). In guinea pig pulmonary artery, sensory neuropeptides (calcitonin gene-related peptide and substance P) are also indicated to be released on PNS and participate in modulation of autonomic adrenergic neurotransmission.The mechanism of PNS-induced release of NO was further investigated and it was indicated that noradrenaline released on PNS could act onendothelium resulting in release of NO.Sensory neuropeptides released on PNS could also participate in endothelial NO release. Additionally, a dilator nerve relasing NO was indicated in guinea pig pulmonary artery. With respect to the mode of endothelin (ET)-1 action, the invivo investigation was done. As a result, secondary release of cyclo-oxygenase-generated eicosanoid(s), mainly thromboxane A_2 was suggested to be responsible for the pressor response of ET-1. The interactions between ET-1 and other vasoactive autacoids were examined employing cultured endothelial cells and increase in the level of prostacyclin (6-keto-prostaglandin F_<1alpha>) was observed in the culture media after administration of endothelin-1. The interactions between other autacoids are being investigated.