Prusa Alexander M, Plass Christian A
Department of Surgery, Medical University of Vienna, Austria.
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Austria.
Saudi Pharm J. 2017 Nov;25(7):993-998. doi: 10.1016/j.jsps.2017.03.007. Epub 2017 Mar 25.
Cigarette smoking not only has a carcinogenic effect but also leads to an increase in arterial blood pressure. Besides its main components, i.e. nicotine, tar, and carbon monoxide, cigarette smoke also contains thiocyanate. Thiocyanate anions (SCN) arise from the detoxification of hydrogen cyanide and its plasma concentrations were found to correlate significantly with cigarette consumption. There is also evidence that atherosclerotic disease progression is much more rapid when serum SCN levels are increased. Melatonin, a non-toxic indolamine with various physiologic functions, is believed to protect against inflammatory processes and oxidative stress. It has been demonstrated that melatonin serves as free radical scavenger and represents a potent antioxidant. Therefore, it is believed that melatonin with its atheroprotective effects may be useful either as a sole therapy or in conjunction with others. The aim of this study was to quantify the thiocyanate-induced vasomotor response in aortic tissue and further to examine the potential of melatonin in affecting the generated vasoreactivity. Aortic rings of adult male normotensive Wistar rats were cut into 4-mm rings. Following the administration of thiocyanate in various concentrations, vasomotor response of aortic vessel segments was measured. To assess the effect of melatonin on vasomotor activity, organ bath concentrations were modulated from 60 to 360 pM, which corresponds to physiologic plasma up to the levels of patients with regular oral intake of 3 mg of melatonin as a supplement. Thirty-six rat aortic rings were studied. When exposed to thiocyanate, vessel segments revealed vasoconstriction in a concentration-dependent manner. In rings which were preincubated with melatonin at a concentration of 360 pM, a 56.5% reduction of effect size could be achieved (4.09 ± 1.22 mN versus 9.41 ± 1.74 mN, P < 0.0001). Additionally, administration of 360 pM melatonin at a norepinephrine concentration of 80 mM resulted in a relaxation of 10.9 ± 2.2%. The vasodilatatory effect of melatonin was significantly reduced to 1.3 ± 0.5% when concentration of norepinephrine was doubled (P < 0.002). This study indicates that vessel segments that were exposed to thiocyanate responded with a dose-dependent vasoconstriction. The effect could be markedly attenuated in segments preincubated in melatonin.
吸烟不仅具有致癌作用，还会导致动脉血压升高。除了其主要成分，即尼古丁、焦油和一氧化碳外，香烟烟雾中还含有硫氰酸盐。硫氰酸根阴离子（SCN）来自氰化氢的解毒过程，其血浆浓度与吸烟量显著相关。也有证据表明，当血清硫氰酸盐水平升高时，动脉粥样硬化疾病的进展会更快。褪黑素是一种具有多种生理功能的无毒吲哚胺，被认为可以抵御炎症过程和氧化应激。已经证明褪黑素可以作为自由基清除剂，是一种有效的抗氧化剂。因此，人们认为具有抗动脉粥样硬化作用的褪黑素可能单独使用或与其他药物联合使用都有用。本研究的目的是量化硫氰酸盐诱导的主动脉组织血管运动反应，并进一步研究褪黑素影响所产生的血管反应性的潜力。将成年雄性正常血压Wistar大鼠的主动脉环切成4毫米的环。给予不同浓度的硫氰酸盐后，测量主动脉血管段的血管运动反应。为了评估褪黑素对血管运动活性的影响，将器官浴中的浓度从60皮摩尔调制到360皮摩尔，这相当于正常生理血浆浓度，直至定期口服3毫克褪黑素补充剂的患者的血浆浓度水平。共研究了36个大鼠主动脉环。当暴露于硫氰酸盐时，血管段呈现出浓度依赖性的血管收缩。在预先用360皮摩尔浓度的褪黑素孵育的环中，效应大小可降低56.5%（4.09±1.22毫牛顿对9.41±1.74毫牛顿，P<0.0001）。此外，在去甲肾上腺素浓度为80微摩尔时给予360皮摩尔的褪黑素，可导致10.9±2.2%的舒张。当去甲肾上腺素浓度加倍时，褪黑素的血管舒张作用显著降低至1.3±0.5%（P<0.002）。本研究表明，暴露于硫氰酸盐的血管段会出现剂量依赖性血管收缩。在预先用褪黑素孵育的血管段中，这种效应可明显减弱。
