Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium.
Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium.
复制标题
LY83583、去甲二氢愈创木酸和奎纳克林对兔主动脉和左心房环 GMP 升高和毒蕈碱激动剂张力抑制的影响。
DOI：
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发表时间：
1987
影响因子：
2.1
通讯作者：
J. Diamond
中科院分区：
文献类型：
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作者：
J. Diamond
毒蕈碱受体激动剂引起的环GMP升高被认为是这些药物在心肌中的负性肌力作用以及这些药物在血管平滑肌中引起的内皮依赖性松弛的原因。在环GMP降低剂LY83583存在和不存在的情况下，通过监测毒菌碱激动剂对兔左心房带和主动脉环张力和环GMP水平的影响，研究了这些关系。LY83583完全阻断乙酰胆碱在内皮细胞完整的兔主动脉环中引起的环状GMP增加和松弛。乙酰胆碱诱导的环GMP升高和松弛也被奎尼卡因和去甲二氢愈木酸（NDGA）阻断，但这两种反应都没有被5-脂氧合酶抑制剂U-60257阻断。在兔左心房实验中，LY83583阻断了乙酰胆碱诱导的环GMP升高，但没有阻断药物的负性肌力作用。Quinacrine、NDGA和鸟苷酸环化酶抑制剂亚甲基蓝均不能阻断甲乙醇引起的心房条环GMP升高或收缩力降低。这些结果支持了这样的观点，即环GMP的增加可能是毒蕈碱受体激动剂对兔主动脉内皮依赖性松弛的原因，而不是这些药物对兔心房的直接负性肌力作用的原因。毒蕈碱类药物似乎通过不同的机制增加兔心房和主动脉的环GMP水平。虽然两者都被LY83583阻断，但它们不仅对内皮细胞的要求不同，而且对其他阻断剂的易感性也不同。
Elevation of cyclic GMP by muscarinic agonists has been suggested to be responsible for the negative inotropic effects of these agents in cardiac muscle, and for the endothelium-dependent relaxation caused by these agents in vascular smooth muscle. These relationships were studied by monitoring the effects of muscarinic agonists on tension and cyclic GMP levels in rabbit left atrial strips and aortic rings, in the presence and absence of the cyclic GMP lowering agent, LY83583. LY83583 completely blocked both the cyclic GMP increase and the relaxation caused by acetylcholine in rabbit aortic rings with intact endothelial cells. Acetylcholine-induced cyclic GMP elevation and relaxation in these preparations were also blocked by quinacrine and nordihydroguaiaretic acid (NDGA), but neither response was blocked by the 5-lipoxygenase inhibitor U-60257. In the experiments with rabbit left atrium, LY83583 blocked the acetylcholine-induced cyclic GMP elevation but did not block the negative inotropic effects of the drug. Quinacrine, NDGA, and a guanylate cyclase inhibitor, methylene blue, failed to block either the cyclic GMP increase or the decrease in contractile force caused by carbachol in atrial strips. These results support the suggestion that an increase in cyclic GMP may be responsible for the endothelium-dependent relaxation of rabbit aorta by muscarinic agonists, but not for the direct negative inotropic effects of these drugs in rabbit atrium. Muscarinic agents appear to increase cyclic GMP levels in rabbit atrium and aorta by different mechanisms. Although both are blocked by LY83583, they differ not only in their requirements for endothelial cells, but also in their susceptibility to other blocking agents.