Activation of heme-free soluble guanylate cyclase with cinaciguat has beneficial cardiorenal actions when added to furosemide in experimental heart failure

Background Volume overload and sodium retention in congestive heart failure (HF) are usually treated with loop diuretics. However, worsening renal function is frequently observed and is associated with worse outcomes. Soluble guanylyl cyclase (sGC) plays an important role in renal function. Importantly, sGC activation can be impaired in cardiorenal disease states, which can be due to not only decreased bioavailability of nitric oxide but also to heme oxidation or heme loss of sGC, which renders the enzyme insensitive to NO. Cinaciguat is a novel sGC activator that stimulates the heme-free, NO-insensitive form of sGC.