CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels
CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels
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DOI：
10.3317/jraas.2006.014
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发表时间：
2006-06
影响因子：
2.9
通讯作者：
Robinder S. Garcha;A. Hughes
中科院分区：
文献类型：
--
作者：
Robinder S. Garcha;A. Hughes
利钠肽在钠调节和血压控制中起重要作用。本实验观察了心钠素（ANP）、脑钠素（BNP）和C型钠素（CNP）对人离体阻力动脉的作用，并探讨了其舒张血管的机制。将人皮下阻力动脉固定在等长肌描记器中，并用苯肾上腺素收缩。CNP，而不是ANP或BNP，以浓度依赖性方式舒张动脉。CNP的作用不受内皮去除、NG-单甲基精氨酸抑制一氧化氮合酶或1H-[1，2，4]恶二唑并[4，3-α]喹喔啉-1-酮抑制可溶性鸟苷酸环化酶的影响。通过8-溴鸟苷-3 '，5'-环状硫代磷酸酯，Rp-异构体（Rp-8-Br-cGMPS）阻断环状GMP依赖性激酶可抑制CNP松弛。高钾或伊比利亚毒素也抑制CNP舒张，表明这是由于BKCa通道开放。奥马曲拉是一种血管肽酶抑制剂，能增强CNP的作用，并抑制对Ang I的反应。总之，CNP（而非ANP或BNP）通过激活环GMP依赖性激酶和BKCa来舒张人阻力动脉。CNP的作用通过血管肽酶抑制作用增强，这可能有助于这些药物在体内的血管扩张作用。由于CNP广泛存在于内皮细胞中，因此其在生理和病理情况下可能在调节人外周阻力中起作用。
Natriuretic peptides play an important role in sodium regulation and blood pressure (BP) control. We examined the effects of atrial natriuetic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) on human isolated resistance arteries and the mechanisms involved in vasorelaxation. Human subcutaneous resistance arteries were mounted in an isometric myograph and contracted with phenylephrine. CNP, but not ANP or BNP, relaxed arteries in a concentration dependent manner. The action of CNP was unaffected by removal of the endothelium, inhibition of nitric oxide synthase by NG-monomethyl-Larginine or inhibition of soluble guanylate cyclase by 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Blockade of cyclic GMP-dependent kinase by 8- bromoguanosine-3', 5'- cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cGMPS) inhibited CNP relaxation. CNP relaxation was also inhibited by high potassium or iberiotoxin, indicating that it was due to opening of BKCa channels. Omapatrilat, a vasopeptidase inhibitor of neutral endopeptidase and angiotensin-converting enzyme, enhanced the effect of CNP and inhibited responses to Ang I. In summary, CNP, but not ANP or BNP, relaxes human resistance arteries by activating cyclic GMP-dependent kinase and BKCa. The effects of CNP are enhanced by vasopeptidase inhibition and this may contribute to the vasodilator effects of these agents in vivo. Since CNP is widely present in endothelium it may play a role in the regulation of peripheral resistance in man in physiological and pathological circumstances.