Fung H L, Poliszczuk R
Z Kardiol. 1986;75 Suppl 3:25-7.
Our studies on Sprague-Dawley rats showed that, in aortic tissues, nitrate tolerance is accompanied by reduced production of the 1,2-glyceryl dinitrate metabolite. This reduced vascular metabolism is consistent with the view that intracellular metabolic processes occur prior to vasodilation. The individual roles of the denitrated metabolites in nitrate tolerance are still unclear. S-nitroso N-acetyl penicillamine retains its vasodilating properties toward blood vessels which have been made tolerant toward nitroglycerin. This finding is consistent with the Ignarro Nitrosothiol Hypothesis for nitrate action. Further studies are being conducted in our laboratory to determine whether nitrosothiols are indeed non-tolerance producing "nitrates" and whether they possess suitable pharmaceutical and toxicological properties for them to become therapeutic agents themselves.
我们对斯普拉格-道利大鼠的研究表明，在主动脉组织中，硝酸酯耐受性伴随着1,2-二硝酸甘油酯代谢物生成的减少。这种血管代谢的降低与细胞内代谢过程先于血管舒张发生的观点一致。脱硝代谢物在硝酸酯耐受性中的个体作用仍不清楚。S-亚硝基-N-乙酰青霉胺对已对硝酸甘油产生耐受性的血管仍保留其血管舒张特性。这一发现与伊格纳罗的亚硝基硫醇硝酸酯作用假说相符。我们实验室正在进行进一步研究，以确定亚硝基硫醇是否确实是不产生耐受性的“硝酸盐”，以及它们是否具有合适的药学和毒理学特性使其自身成为治疗剂。
