硝普钠与异丙肾上腺素松弛犬气管平滑肌的协同作用

目的：研究硝普钠（ＳＮＰ）与异丙肾上腺素（ＩＳＯ）对犬气管平滑肌松弛作用是否存在协同关系，并分析协同的机制。方法：采用放射免疫分析法测定犬气管平滑肌环核苷酸量，并用磷酸二酯酶（ＰＤＥ）同工酶抑制剂为工具分析ＳＮＰ与ＩＳＯ相互作用的机制。结果：ＳＮＰ（１～１００μｍｏｌ·Ｌ－１）增强ＩＳＯ（３０μｍｏｌ·Ｌ－１）对３μｍｏｌ·Ｌ－１乙酰甲胆碱预收缩的犬气管平滑肌的松弛作用。ＳＮＰ（１００μｍｏｌ·Ｌ－１）与ＩＳＯ（３０μｍｏｌ·Ｌ－１）对犬气管平滑肌松弛的协同作用伴有气管平滑肌中ｃＡＭＰ积聚比ＳＮＰ与ＩＳＯ单独时分别增加１．２倍与０．４倍。ＰＤＥⅤ抑制剂扎普司特（３μｍｏｌ·Ｌ－１）使ＳＮＰ的气管平滑肌ｃＧＭＰ积聚由２．４倍增加到４．６倍，可进一步增加气管松弛作用１．２倍。合并ＰＤＥⅢ抑制剂氰胍哒嗪（３０μｍｏｌ·Ｌ－１）和ＰＤＥⅣ抑制剂咯利普兰（３０μｍｏｌ·Ｌ－１）或合并ＳＮＰ（１００μｍｏｌ·Ｌ－１）和咯利普兰（３０μｍｏｌ·Ｌ－１）均能进一步增强ＩＳＯ的气管ｃＡＭＰ积聚与松弛作用。结论：ＳＮＰ是通过气管平滑肌ｃＧＭＰ含量增加而抑制ＰＤＥⅢ，导致ＳＮＰ与ＩＳＯ对气管松弛的协同作用。

The mechanism of synergistic action of relaxation of canine trachealis induced by sodium nitroprusside and isoproterenol

AIM: To evaluate the synergistic action of sodium nitroprusside (SNP) and isoproterenol (ISO) on canine trachealis, and to explore the mechanism of synergism. METHODS: Radioimmunoassay was used to assess the amount of cyclic nucleotide in trachealis and phosphodiesterase (PDE) isozyme inhibitors were used as tools. RESULTS: SNP(1￣100 μmol·L -1 ) potentiated ISO (30 μmol·L -1 ) induced relaxation in canine trachealis contracted by methacholine (3 μmol·L -1 ). Synergistic actions of SNP (100 μmol·L -1 ) and ISO (30 μmol·L -1 ) on canine tracheal relaxation were accompanied by 1 2 and 0 4 fold increments of cAMP content of tracheal smooth muscle compared with SNP and ISO alone, respectively. M&B 22948 (3 μmol·L -1 ), an inhibitor of PDE Ⅴ, increased cAMP accumulation and tracheal relaxation in response to SNP by 4 6 and 1 2 fold, respectively. The PDE Ⅲ inhibitor SK&F 94836 (30 μmol·L -1 ) combined with the PDE Ⅳ inhibitor rolipram (30 μmol·L -1 ) or SNP (100 μmol·L -1 ) combined with SK&F 94836 (30 μmol·L -1 ) increased more ISO induced cAMP accumulation and tracheal relaation than did SK&F 94836, rolipram of SNP. CONCLUSION: The synergistic action of SNP and ISO on canine trachealis is due to inhibition of PDE Ⅲ by SNP induced cGMP accumulation.