Booth B P, Brien J F, Marks G S, Nakatsu K
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, ON, Canada.
Can J Physiol Pharmacol. 1993 Aug;71(8):629-32. doi: 10.1139/y93-091.
It has previously been shown that the vasodilatory response to glyceryl trinitrate (GTN) was decreased during hypothermic cardiopulmonary bypass. The purpose of these experiments was to determine the effect of temperature on GTN-induced relaxation and on GTN biotransformation in rabbit aorta. It was determined that the EC50 of GTN on rabbit aortic rings (RARs) was increased significantly from 1.8 x 10(-8) M at 37 degrees C to 3.4 x 10(-8) M at 27 degrees C (p < 0.05). The production of NO by rabbit aortic strips (RASs) was significantly less at 27 degrees C compared with 37 degrees C after 80 min, being 9.62 x 10(-11) +/- 13.2 x 10(-11) mol NO/g wet wt. RASs compared with 5.71 x 10(-10) +/- 9.43 x 10(-11) mol NO/g wet wt. RASs, respectively (p < 0.05), after 80 min incubation. There was no difference in the amount of glyceryl-1,2-dinitrate (1,2-GDN) produced from GTN at the two temperatures. The ED20 for NO-induced relaxation of RARs increased from 3.46 x 10(-10) +/- 2.24 x 10(-10) mol at 37 degrees C to 1.01 x 10(-9) +/- 4.51 x 10(-10) mol at 27 degrees C (p < 0.05). These data indicate that the biotransformation of GTN and the release of NO were impaired by hypothermia, and that this, as well as a decrease in the tissue response to NO at 27 degrees C, explains the decrease in GTN activity at reduced body temperatures.
先前的研究表明，在低温体外循环期间，对硝酸甘油（GTN）的血管舒张反应会降低。这些实验的目的是确定温度对兔主动脉中GTN诱导的舒张以及GTN生物转化的影响。结果发现，GTN对兔主动脉环（RARs）的半数有效浓度（EC50）从37℃时的1.8×10⁻⁸M显著增加至27℃时的3.4×10⁻⁸M（p<0.05）。80分钟后，与37℃相比，27℃时兔主动脉条（RASs）产生的一氧化氮（NO）显著减少，分别为9.62×10⁻¹¹±13.2×10⁻¹¹mol NO/g湿重的RASs和5.71×10⁻¹⁰±9.43×10⁻¹¹mol NO/g湿重的RASs（p<0.05）。在这两个温度下，由GTN产生的甘油-1,2-二硝酸酯（1,2-GDN）量没有差异。NO诱导RARs舒张的半数有效剂量（ED20）从37℃时的3.46×10⁻¹⁰±2.24×10⁻¹⁰mol增加至27℃时的1.01×10⁻⁹±4.51×10⁻¹⁰mol（p<0.05）。这些数据表明，低温会损害GTN的生物转化和NO的释放，并且这一点，以及27℃时组织对NO反应的降低，解释了体温降低时GTN活性的下降。
