An approach to understand the pathogenesis of coronary artery spasm by molecular and cellular biology techniques

在这两年中，我们取得了以下成果。(1)本文研究了动脉粥样硬化（AS）和对照（C）家兔动脉的收缩和磷脂酰肌醇（PI）转换。与C相比，AS中的5-HT刺激表现出增强的收缩和PI标记，尽管NE诱导的收缩和PI标记在两组中是相同的。提示动脉粥样硬化时存在5-HT介导的过度收缩和信号转导异常。(2)本文观察了内皮源性舒张因子（EDRF）对组胺（HA）引起的兔胸主动脉收缩和PI转换的影响。HA表现出收缩和[^<32>P]Pi掺入PI。去除内皮和亚甲蓝可增强HA诱导的收缩和PI标记。这些结果表明，PI周转和收缩响应HA的负反馈EDRF调节。(3)天然低密度脂蛋白（LDL）和修饰LDL的抑制作用， ...更多信息 本文观察了铜氧化和磷脂酶A_2（PLA_2）对兔胸主动脉内皮依赖性舒张（EDR）的影响。天然LDL对ACh诱导的EDR无影响，而PLA_2处理的LDL和氧化LDL则抑制EDR。此外，外源性给予合成LPC对EDR具有有效的抑制作用。这些结果表明LPC是氧化LDL抑制作用的主要物质。(4)测定兔主动脉溶血磷脂酶活性。这种酶的激活不需要Ca^&lt;2+&gt;.胆固醇抑制溶血磷脂酶活性。这些结果可能意味着溶血磷脂酶活性的抑制胆固醇的重要性，作为负责机制的LPC在动脉粥样硬化血管中的积累增加。(5)本文比较了正常和动脉粥样硬化（AS）兔动脉对人心钠素（hANP）的舒张反应。AS时hANP诱导的血管舒张和cGMP生成明显减少。这些结果表明，hANP通过膜结合鸟苷酸环化酶系统诱导的血管舒张反应在AS动脉中受损。少

We obtained the following results in these 2 years.(1) Contraction and Phosphoinositides(PI) turnover were studied in atherosclerotic(AS) and control(C) rabbit aortas. Stimulation with 5-HT in AS exhibited augmented contraction and PI labeling compared with C, although NE-induced contraction and PI labeling were identical in both groups. These results indicate that 5-HT-mediated hypercontraction and signal transduction abnormality were present in atherosclerotic arteries.(2) Effects of endothelium-derived relaxing factor(EDRF) on histamine(HA)-induced vasocsustriction and PI turnover were studied in rabbit thoracic aorta. HA exhibited contraction and [^<32>P]Pi incorporation into PI. Removal of the endothelium and methylene blue potentiate the contraction and PI labeling induced by HA. These results suggest that PI turnover and contraction in response to HA were regulated by the negative feedback EDRF.(3) The inhibitory effects of native low density lipoprotein(LDL) and modified LDL wi … More th copper oxidation and phospholipase A_2(PLA_2) on endothelium-dependent relaxation(EDR) were examined in rabbit thoracic aorta. Native LDL had no effects on ACh-induced EDR, whereas PLA_2 treated LDL and oxidized LDL inhibited EDR. Furthermore, exogeneous administration of synthetic LPC had a potent inhibitory action on EDR. These results indicate that LPC is the principal substance for the inhibitory effect of oxidized LDL.(4) Lysophospholipase activity was measured in rabbit aorta. The enzyme did not require Ca^<2+> for its activation. Cholesterol inhibited the lysophospholipase activity. These results may imply the importance of the lysophospholipase activity inhibition by cholesterol as the responsible mechanisms for the enhanced accumulation of LPC in atherosclerotic vessels.(5) The vasodilatory response to human arterial natriuretic peptide(hANP) were compared between normal and atherosclerotic(AS) rabbit aortas. The hANP-induced relaxation and cyclic GMP formation in AS were markedly reduced. These results suggest that hANP-induced vasodilating response through membrane-bound guanylate cyclase system is impaired in AS arteries. Less