New insights into the role of soluble guanylate cyclase in blood pressure regulation.

PURPOSE OF REVIEW Nitric oxide (NO)-soluble guanylate cyclase (sGC)-dependent signaling mechanisms have a profound effect on the regulation of blood pressure (BP). In this review, we will discuss recent findings in the field that support the importance of sGC in the development of hypertension. RECENT FINDINGS The importance of sGC in BP regulation was highlighted by studies using genetically modified animal models, chemical stimulators/activators and inhibitors of the NO/sGC signaling pathway, and genetic association studies in humans. Many studies further support the role of NO/sGC in vasodilation and vascular dysfunction, which is underscored by the early clinical success of synthetic sGC stimulators for the treatment of pulmonary hypertension. Recent work has uncovered more details about the structural basis of sGC activation, enabling the development of more potent and efficient modulators of sGC activity. Finally, the mechanisms involved in the modulation of sGC by signaling gases other than NO, as well as the influence of redox signaling on sGC, have been the subject of several interesting studies. SUMMARY sGC is fast becoming an interesting therapeutic target for the treatment of vascular dysfunction and hypertension, with novel sGC stimulating/activating compounds as promising clinical treatment options.