Ataciguat is a nitric oxide-independent soluble guanylate cyclase (sGC) activator. Ataciguat activates the oxidized heme iron redox form of sGC to stimulate cGMP production. Ataciguat can be used in research related to heart failure and aortic valve stenosis[1-4].
In vitro, Ataciguat (0.1–10μM) was used to treat HUVEC cells for 30 minutes. Ataciguat significantly increased NO production in the cells[5]. Rat aortic smooth muscle cells were pretreated with H₂O₂ (500μM) for 1 hour, followed by treatment with Ataciguat (10μM) for 15 minutes. Ataciguat significantly increased cGMP production in the cells[6].
In vivo, Ataciguat (10mg/kg; twice daily) was administered by gavage to adult male Wistar rats with chronic myocardial infarction induced by coronary ligation for 10 weeks. Ataciguat significantly improved vascular function and reduced platelet activation[7]. Ataciguat (10mg/kg; once daily) was subcutaneously injected into C57Bl/6J mice with pulmonary arterial hypertension induced by chronic hypoxia for 14 days (from day 21 to day 35 of hypoxia). Ataciguat significantly reduced pulmonary arterial hypertension and right ventricular hypertrophy[8].
References:
[1] Schindler U, Strobel H, Schönafinger K, et al. Biochemistry and pharmacology of novel anthranilic acid derivatives activating heme-oxidized soluble guanylyl cyclase. Mol Pharmacol. 2006 Apr;69(4):1260-8.
[2] Çakmak E, Yönem Ö, Saraç B, et al. Comparative Relaxant Effects of Ataciguat and Zaprinast on Sheep Sphincter of Oddi. Balkan Med J. 2016 Jul;33(4):453-7.
[3] Zhang B, Enriquez-Sarano M, Schaff HV, et al. Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy. Circulation. 2025 Apr;151(13):913-930.
[4] Fraccarollo D, Galuppo P, Motschenbacher S, et al. Soluble guanylyl cyclase activation improves progressive cardiac remodeling and failure after myocardial infarction. Cardioprotection over ACE inhibition. Basic Res Cardiol. 2014 Jul;109(4):421.
[5] Martinelli AM, Rodrigues CNDS, Moraes TF, et al. In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation. J Pharm Pharm Sci. 2018;21(1):38-45.
[6] Zhou Z, Pyriochou A, Kotanidou A, et al. Soluble guanylyl cyclase activation by HMR-1766 (ataciguat) in cells exposed to oxidative stress. Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1763-71.
[7] Schäfer A, Fraccarollo D, Werner L, et al. Guanylyl cyclase activator ataciguat improves vascular function and reduces platelet activation in heart failure. Pharmacol Res. 2010 Nov;62(5):432-8.
[8] Weissmann N, Hackemack S, Dahal BK, et al. The soluble guanylate cyclase activator HMR1766 reverses hypoxia-induced experimental pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L658-65.