Ahlner J, Axelsson K L
Drugs. 1987;33 Suppl 4:32-8. doi: 10.2165/00003495-198700334-00007.
The nitrates used therapeutically in angina pectoris and congestive heart failure are, from a chemical point of view, organic nitroesters. Their principal pharmacological effect is vascular smooth muscle relaxation, leading to vasodilation, which explains their therapeutic effects. Several mechanisms have been proposed for their mode of action at the cellular level, in order to explain vascular smooth muscle relaxation. Today, there is strong evidence that organic nitroesters stimulate the enzyme guanylate cyclase in the smooth muscle cell. This enzyme produces a cyclic nucleotide, cyclic guanosine-3',5'-monophosphate (cGMP), which in turn eventually lowers the free calcium concentration in the cytosol to induce relaxation. The exact mechanism by which the organic nitroesters stimulate guanylate cyclase is still obscure. Preliminary results from our laboratory indicate that there may be more than one mechanism responsible for the activation of the enzyme. Knowledge of the mode of action at the cellular level is probably important in order to understand the mechanism(s) behind the development of tolerance towards the organic nitroesters.
从化学角度来看，用于治疗心绞痛和充血性心力衰竭的硝酸盐类属于有机硝酸酯。它们的主要药理作用是使血管平滑肌松弛，从而导致血管舒张，这就解释了它们的治疗效果。为了解释血管平滑肌松弛现象，人们在细胞水平上提出了几种作用机制。如今，有充分证据表明有机硝酸酯可刺激平滑肌细胞中的鸟苷酸环化酶。这种酶会产生一种环核苷酸，即环磷酸鸟苷（cGMP），而cGMP最终会降低细胞质中的游离钙浓度以诱导平滑肌松弛。有机硝酸酯刺激鸟苷酸环化酶的确切机制仍不清楚。我们实验室的初步结果表明，可能有不止一种机制负责激活该酶。了解细胞水平的作用方式对于理解对有机硝酸酯产生耐受性背后的机制可能很重要。
