C-type natriuretic peptide modulates permeability of the blood–brain barrier

C型利钠肽(CNP)在脑内含量丰富，但其对血脑屏障(BBB)通透性的影响尚未阐明。在这里，我们研究了这种影响。CNP可剂量依赖性地降低体外BBB模型的跨内皮细胞电阻(TEER)。CNP处理后，ZO-1的信使RNA和蛋白表达均降低。环鸟苷(CGMP)类似物8-bromo-cGMP对ZO-1的TEER、mRNA和蛋白质表达的影响可被蛋白激酶G(PKG)抑制剂RP-8-CPT-cGMPS逆转，从而提示PKG和cGMP信号在血脑屏障功能中的作用。静脉注射荧光素钠对小鼠脑内荧光分析的体内研究也表明，CNP显著增加了血脑屏障的通透性。这些结果表明，CNP通过改变ZO-1来调节血脑屏障通透性。

C-type natriuretic peptide (CNP) is abundant in brain, but its effect on blood-brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, was significantly dose dependently decreased by CNP. CNP treatment reduced both the messenger RNA and protein expressions of zonula occludens-1 (ZO-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS, thus implying the role of PKG and cGMP signaling in BBB function. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein also showed a significant increase in BBB permeability by CNP. These findings suggest that CNP modulates the BBB permeability by altering ZO-1.