异氟醚通过非钙依赖性PKC途径增强肾动脉平滑肌收缩

Isoflurane mediates renal artery smooth muscle contraction through Ca～(2+)-indepentdent PKC signaling pathway

目的探讨异氟醚引发肾动脉血管平滑肌收缩的直接作用机制。方法去内皮肾动脉环,3%皂甙处理使膜通透,咖啡因诱除内质网存贮钙,利用10-6M钙离子浓度EGTA缓冲液使肾动脉环压缩达平衡,加入不同浓度异氟醚EGTA缓冲溶液,观察动脉环张力变化,然后使用含PKC抑制剂BIM或G觟6976的EGTA缓冲液替代原溶液,观察动脉环张力变化。结果 1%、3%和5%不同浓度异氟醚,均能使压缩达平衡的肾动脉环张力进一步增强,且与异氟醚浓度呈剂量依赖性。PKC抑制剂BIM可以抑制异氟醚的作用,钙依赖性PKC抑制剂G觟6976则无此作用。结论异氟醚能通过不升高胞内钙浓度的方式增强肾动脉血管平滑肌的收缩,可能是通过非钙依赖性PKC介导的。

【Objective】To study the direct effect of isoflurane on the contraction of renal artery smooth muscle and its mechanism.【Method】Rabbit renal artery strips were treated with 3%～5% saponin to make the sarcolemma permeable,after equilibrium in 10-6 M Ca2＋-EGTA buffer,the calcium stored in reticulum（SR） was released due to application of caffeine.Stead state tense was obtained when the strips were soaked in submaximal calcium concentration buffer.Then the submaximal calcium concentration buffer with various concentration isoflurane and/or 10μM BIM was used,the tension variety was detected by computer.【Result】1%,3%,5% isoflurane made rabbit renal artery strips further contract after they had reached equilibrium,and the tension altitude was isoflurane concentration dependent.This effect of isoflurane was inhibited by BIM,a kind inhibitor for both Ca dependent and independent PKC kinase subtypes,but not inhibited by G-6976,a kind inhibitor for Ca dependent PKC.【Conclusion】Isoflurane could increase renal artery smooth muscle contraction in a way not rising the sarcoplasm calcium,but Ca-independent PKC signaling pathway may be involved.