de la Lande Ivan S, Siebert Tracey E, Bennett Catherine L, Stafford Irene, Horowitz John D
Cardiology Unit, The Queen Elizabeth Hospital Campus, North Western Adelaide Health Service, The University of Adelaide, 28 Woodville Road, Woodville South, South Australia, 5011, Australia.
Eur J Pharmacol. 2004 Feb 20;486(2):201-7. doi: 10.1016/j.ejphar.2003.12.027.
The influence of the endothelium on glyceryl trinitrate metabolism and relaxation and the relationship to tolerance induced by transdermal glyceryl trinitrate was explored in rat aorta. Metabolism was assessed in artery segments incubated with glyceryl trinitrate (1.0 microM) for 2 min and the contents of 1,2- and 1,3-glyceryl dinitrate measured by gas chromatography. In non-tolerant arteries mean contents of glyceryl trinitrate, 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate were 3.2, 0.23 and 0.10 nmol/g, respectively; in tolerant arteries the content of 1,2-glyceryl dinitrate was reduced by approximately 60%. Endothelium removal or nitric oxide synthase (NOS) inhibition did not affect metabolite contents but increased the relaxant response to glyceryl trinitrate in the tolerant artery to an extent that tolerance was significantly attenuated. It is concluded that (i) tolerance is associated with depression of glyceryl trinitrate metabolism by an endothelium-independent mechanism and (ii) the endothelium contributes to tolerance by a mechanism which is independent of metabolism and may be linked with endothelial NOS.
在大鼠主动脉中研究了内皮对硝酸甘油代谢、舒张作用的影响以及与经皮硝酸甘油诱导的耐受性的关系。在与硝酸甘油（1.0微摩尔）孵育2分钟的动脉段中评估代谢情况，并通过气相色谱法测量1,2-二硝酸甘油酯和1,3-二硝酸甘油酯的含量。在非耐受性动脉中，硝酸甘油、1,2-二硝酸甘油酯和1,3-二硝酸甘油酯的平均含量分别为3.2、0.23和0.10纳摩尔/克；在耐受性动脉中，1,2-二硝酸甘油酯的含量降低了约60%。去除内皮或抑制一氧化氮合酶（NOS）并不影响代谢产物含量，但增加了耐受性动脉对硝酸甘油的舒张反应，以至于耐受性显著减弱。得出的结论是：（i）耐受性与硝酸甘油代谢受内皮非依赖性机制抑制有关；（ii）内皮通过一种独立于代谢且可能与内皮NOS相关的机制促成耐受性。
