Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors
Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors
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DOI：
10.1172/jci11218
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发表时间：
2001-05-01
影响因子：
15.9
通讯作者：
Nasjletti, A
中科院分区：
文献类型：
--
作者：
Kaide, J;Zhang, F;Nasjletti, A
大鼠肾叶间动脉表达血红素加氧酶 2 (HO-2) 并产生一氧化碳 (CO)，并释放到顶部空间气体中。在用铬中卟啉 (CrMP) 抑制 HO 活性或用反义寡脱氧核苷酸 (HO-2 AS-ODN) 抑制 HO-2 表达后，CO 释放分别降至对照的 30% 和 54%。膜片钳研究表明，CrMP 降低了叶间动脉平滑肌细胞中四乙铵敏感（TEA 敏感）105 pS K 通道的开放概率，并且 CrMP 的这种作用可被 CO 逆转。对去氧肾上腺素诱导的张力发展的评估显示，用 HO-2 AS-ODN、CrMP 或 TEA 处理的血管中 EC50 降低。外源性 CO 极大地降低了对减少血管 CO 产生的激动剂诱导的收缩的敏化作用，但不会降低 TEA 阻断 K 通道的敏化作用。总的来说，这些数据表明，血管 CO 通过涉及 TEA 敏感 K 通道的机制，充当血管收缩剂血管反应性的抑制调节剂。
Rat renal interlobar arteries express heme oxygenase 2 (HO-2) and manufacture carbon monoxide (CO), which is released into the headspace gas. CO release falls to 30% and 54% of control, respectively after inhibition of HO activity with chromium mesoporphyrin (CrMP) or of HO-2 expression with antisense oligodeoxynucleotides (HO-2 AS-ODN). Patch-clamp studies revealed that CrMP decreases the open probability of a tetraethylammonium-sensitive (TEA-sensitive) 105 pS K channel in interlobar artery smooth muscle cells, and that this effect of CrMP is reversed by CO. Assessment of phenylephrine-induced tension development revealed reduction of the EC50 in vessels treated with HO-2 AS-ODN, CrMP, or TEA. Exogenous CO greatly minimized the sensitizing effect on agonist-induced contractions of agents that decrease vascular CO production, but not the sensitizing effect of K channel blockade with TEA. Collectively, these data suggest that vascular CO serves as an inhibitory modulator of vascular reactivity to vasoconstrictors via a mechanism that involves a TEA-sensitive K channel.