Department of Medicine, UCLA School of Medicine, Los Angeles, CA, USA.
Cardiol Rev. 2011 Jan-Feb;19(1):23-9. doi: 10.1097/CRD.0b013e3181fc1c10.
Heart failure (HF) remains a major cause of morbidity and mortality in the United States despite recent advances in its treatment. The nitric oxide -soluble guanylate cyclase (sGC)-cyclic 3', 5'-guanosine monophosphate pathway is a key signaling cascade involved in many physiologic processes. Derangements of the cascade may play an important role in the pathophysiology of HF and other diseases. Organic nitrates, which derive their action from their metabolic conversion to nitric oxide, exploit this pathway therapeutically. They are a mainstay of treatment for acute HF, but the development of tolerance with chronic administration limits their long-term efficacy. The development of a novel class of sGC activators has shown in both animal and preliminary clinical trials to improve hemodynamics without tolerance, while preserving renal function in patients with HF. A phase II clinical program using the sGC activator cinaciguat (BAY 58-2667) is now in progress in patients with symptomatic HF to further evaluate the efficacy and safety of this treatment approach.
尽管心力衰竭（HF）的治疗最近取得了进展，但在美国，它仍然是发病率和死亡率的主要原因。一氧化氮-可溶性鸟苷酸环化酶（sGC）-环 3'，5'-鸟苷酸单磷酸途径是涉及许多生理过程的关键信号级联。级联的紊乱可能在 HF 和其他疾病的病理生理学中起重要作用。有机硝酸盐通过其代谢转化为一氧化氮来发挥作用，从而从治疗上利用该途径。它们是急性 HF 治疗的主要药物，但由于长期给药导致的耐受性限制了其长期疗效。新型 sGC 激活剂的开发在动物和初步临床试验中均表明，在不产生耐受性的情况下改善血液动力学，同时在 HF 患者中保留肾功能。目前正在进行一项使用 sGC 激活剂 cinaciguat（BAY 58-2667）的 II 期临床研究计划，以进一步评估这种治疗方法的疗效和安全性。
