Dombkowski Ryan A, Whitfield Nathan L, Motterlini Roberto, Gao Yan, Olson Kenneth R
Department of Biology, Saint Mary's College, Notre Dame, Indiana, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R141-9. doi: 10.1152/ajpregu.90507.2008. Epub 2008 Nov 12.
Carbon monoxide (CO) is endogenously produced by heme oxygenase (HO) and is involved in vascular, neural, and inflammatory responses in mammals. However, the biological activities of CO in nonmammalian vertebrates is unknown. To this extent, we used smooth muscle myography to investigate the effects of exogenously applied CO (delivered via a water-soluble CO-releasing molecule, CORM-3) on isolated lamprey (Petromyzon marinus) dorsal aortas and examined its mechanisms of action on trout (Oncorhynchus mykiss) efferent branchial (EBA) and celiacomesenteric (CMA) arteries. CORM-3 dose-dependently relaxed all vessels examined. Trout EBA were twofold more sensitive to CORM-3 when precontracted with norepinephrine (NE) than KCl and CORM-3 relaxed five-fold more of the NE- than KCl-induced tension. Glybenclamide (10 microM), an ATP-sensitive potassium channel inhibitor, inhibited NE-induced contraction, but did not affect CORM-3-induced relaxation. NS-2028 (10 microM), a soluble guanylyl cyclase inhibitor, had no effect on a NE-contraction, but inhibited a subsequent CORM-3-induced relaxation. Zinc protopophyrin-IX (ZnPP-IX, 0.3-30 microM), a HO inhibitor, elicited a small, yet dose-dependent and significant, increase in baseline tension but did not have any effect on subsequent NE-induced contractions or a nitric oxide-induced relaxation (via sodium nitroprusside). [ZnPP-IX] greater than 3 microM, however, significantly reduced the predominant vasodilatory response of trout EBA to hydrogen sulfide. These results implicate an active HO/CO pathway in trout vessels having an impact on resting vessel tone and CO-induced vasoactivity that is at least partially mediated by soluble guanylyl cyclase.
一氧化碳（CO）由血红素加氧酶（HO）内源性产生，并参与哺乳动物的血管、神经和炎症反应。然而，CO在非哺乳动物脊椎动物中的生物学活性尚不清楚。在此范围内，我们使用平滑肌肌动描记法研究外源性应用的CO（通过水溶性CO释放分子CORM-3递送）对分离的七鳃鳗（海七鳃鳗）背主动脉的影响，并研究其对虹鳟鱼（虹鳟）传出鳃动脉（EBA）和腹腔肠系膜动脉（CMA）的作用机制。CORM-3剂量依赖性地使所有检测的血管舒张。当用去甲肾上腺素（NE）预收缩时，虹鳟EBA对CORM-3的敏感性是用氯化钾（KCl）预收缩时的两倍，并且CORM-3使NE诱导的张力舒张程度比KCl诱导的张力舒张程度高五倍。格列本脲（10微摩尔），一种ATP敏感性钾通道抑制剂，抑制NE诱导的收缩，但不影响CORM-3诱导的舒张。NS-2028（10微摩尔），一种可溶性鸟苷酸环化酶抑制剂，对NE诱导的收缩无影响，但抑制随后CORM-3诱导的舒张。锌原卟啉-IX（ZnPP-IX，0.3 - 30微摩尔），一种HO抑制剂，引起基线张力小幅但剂量依赖性且显著的增加，但对随后NE诱导的收缩或一氧化氮诱导的舒张（通过硝普钠）没有任何影响。然而，[ZnPP-IX]大于3微摩尔时，显著降低了虹鳟EBA对硫化氢的主要血管舒张反应。这些结果表明虹鳟血管中存在活跃的HO/CO途径，其对静息血管张力和CO诱导的血管活性有影响，且至少部分由可溶性鸟苷酸环化酶介导。
