Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide
Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide
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DOI：
10.1152/ajpheart.00690.2003
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发表时间：
2004-02-01
影响因子：
4.8
通讯作者：
Boor, PJ
中科院分区：
文献类型：
--
作者：
Conklin, DJ;Cowley, HR;Boor, PJ
有研究认为，甲胺（MA）和氨基脲敏感胺氧化酶（SSAO）的活性与糖尿病患者的心血管并发症有关。为了验证这一点，我们1）确定了MA的急性血管活性作用（1- 1，000 mumol/l）在未收缩和去甲肾上腺素中（NE; 1 mumol/l）-用于冠状动脉旁路移植术的预收缩人血管[左乳内动脉（LIMA）、桡动脉（RA）和右隐静脉（RSV）]; 2）使用SSAO抑制剂氨基脲测试LIMA和RSV中的MA效应是否依赖于SSAO活性（1 mmol/l，15 min）测定MA代谢产物甲醛和过氧化氢对LIMA和RSV的影响; 4）测试MA反应是否是一氧化氮、前列腺素或超极化依赖性的; 5）测量MA暴露后的LIMA和RSV cGMP水平;和6）定量LIMA、RA和RSV中的SSAO活性。在NE预收缩的血管中，MA刺激RA和RSV的双相反应（快速收缩，随后延长舒张）和LIMA的主导舒张（平均值+/- SE，%舒张：55.4 +/- 3.9，n = 30）。MA诱导的LIMA舒张是可重复的，无毒的，与年龄无关。在LIMA中，Semanobazide显著阻断MA诱导的舒张（%抑制：82.5 +/- 4.8，n = 7）和SSAO活性（%抑制：98.1 +/- 1.3，n = 26）。甲醛（%松弛：37.3 +/- 18.6，n = 3）和H2 O2（%松弛：55.6 +/- 9.0，n = 9）在1 mmol/l下使NE预收缩的LIMA松弛，与MA相当。MA诱导的LIMA舒张是一氧化氮、前列腺素和可能的cGMP独立的，并被超极化阻断。我们的结论是，血管SSAO活动可能会转换内源性胺，如MA，血管活性代谢产物。
It is hypothesized that methylamine (MA) and semicarbazide-sensitive amine oxidase (SSAO) activity are involved in the cardiovascular complications in human diabetics. To test this, we 1) determined the acute vasoactive effects of MA (1-1,000 mumol/l) in uncontracted and norepinephrine (NE; 1 mumol/l)-precontracted human blood vessels used for coronary artery bypass grafts [ left internal mammary artery (LIMA), radial artery (RA), and right saphenous vein (RSV)]; 2) tested whether MA effects in LIMA and RSV were dependent on SSAO activity using the SSAO inhibitor semicarbazide (1 mmol/l, 15 min); 3) determined the effects of MA metabolites formaldehyde and hydrogen peroxide in LIMA and RSV; 4) tested whether the MA response was nitric oxide, prostaglandin, or hyperpolarization dependent; 5) measured the LIMA and RSV cGMP levels after MA exposure; and 6) quantified SSAO activity in LIMA, RA, and RSV. In NE-precontracted vessels, MA stimulated a biphasic response in RA and RSV (rapid contraction followed by prolonged relaxation) and dominant relaxation in LIMA (mean +/- SE, %relaxation: 55.4 +/- 3.9, n = 30). The MA-induced relaxation in LIMA was repeatable, nontoxic, and age independent. Semicarbazide significantly blocked MA-induced relaxation (%inhibition: 82.5 +/- 4.8, n = 7) and SSAO activity (%inhibition: 98.1 +/- 1.3, n = 26) in LIMA. Formaldehyde (%relaxation: 37.3 +/- 18.6, n = 3) and H2O2 (%relaxation: 55.6 +/- 9.0, n = 9) at 1 mmol/l relaxed NE-precontracted LIMA comparable with MA. MA-induced relaxation in LIMA was nitric oxide, prostaglandin, and possibly cGMP independent and blocked by hyperpolarization. We conclude that vascular SSAO activity may convert endogenous amines, like MA, to vasoactive metabolites.