Soluble guanylate cyclase activation with cinaciguat: a new approach to the treatment of decompensated heart failure.
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.
Department of Medicine, UCLA School of Medicine, Los Angeles, CA, USA.
Shipra
S
Hingorany
William H
WH
Frishman
D000818:Animals; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D020536:Enzyme Activators / Q000627:therapeutic use*; D006162:Guanylate Cyclase / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress
D001565:Benzoates; D020536:Enzyme Activators; D009569:Nitric Oxide; C480588:BAY 58-2667; D006162:Guanylate Cyclase; D006152:Cyclic GMP