Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme in the cardiovascular system and activated by nitric oxide (NO).Nitroglycerin as a well known drug is used for more than a century to prevent heart attacks and is converted in the human body to form NO.However,a lot of limitations and a loss of activity after repeated dosing have limited general use.In the meantime it became apparent that many cardiovascular diseases are associated with a dysfunction of the NO/sGC system.Compounds that stimulate sGC in an NO-independent manner might therefore provide considerable therapeutic advantages.Importantly,two different forms of sGC exist in human cells,the native sGC and heme-free sGC.Recently,we discovered two novel therapeutic principles addressing both forms of sGC.The sGC activators,such as cinaciguat (BAY 58-2667) are capable of selectively activating the haem-free enzyme via binding to the enzymes haem pocket.