Soluble guanylate cyclase (sGC) is the primary cellular receptor for nitric oxide (NO). NO binds and activates a heme group in sGC, initiating the conversion of GTP to the second messenger cyclic GMP (cGMP). BAY-41-8543 is a heme-dependent stimulator of sGC, increasing the activity of recombinant sGC dose-dependently, from 0.1 nM to 100 μM, up to 92-fold.¹ Surprisingly, NO donors synergize with BAY-41-8543 in stimulating recombinant sGC.¹ BAY-41-8543 relaxes vessels and inhibits platelet aggregation in vitro at nM concentrations.¹ In vivo, BAY-41-8543 decreases blood pressure dose-dependently, prolongs bleeding time, and reduces thrombosis.² Inhalation of microparticles containing BAY-41-8543 increases pulmonary vasodilation without changing mean arterial pressure,³ suggesting that agonists of sGC may be efficacious in treating pulmonary hypertension.

1 Stasch, J., Alonso-Alija, C., Apeler, H., et al. Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vitro studies. Br J Pharmacol 135 333-343 (2002).

2 Stasch, J., Dembowsky, K., Perzborn, E., et al. Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies. Br J Pharmacol 135 344-355 (2002).

3 Evgenov, O.V., Kohane, D.S., Bloch, K.D., et al. Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation. Am J Respir Crit Care Med 176 1138-1145 (2007).

Stasch, J., Alonso-Alija, C., Apeler, H., et al. Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vitro studies. Br J Pharmacol 135 333-343 (2002).

Stasch, J., Dembowsky, K., Perzborn, E., et al. Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies. Br J Pharmacol 135 344-355 (2002).

Evgenov, O.V., Kohane, D.S., Bloch, K.D., et al. Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation. Am J Respir Crit Care Med 176 1138-1145 (2007).