Influence of Soluble Guanylate Cyclase on Cardiac, Vascular, and Renal Structure and Function: A Physiopathological Insight

The role of nitric oxide (NO), soluble guanylate cyclase (sGC), and the cyclic guanosine monophosphate (cGMP) pathway in cardiovascular and renal health and disease is a complex issue. The impact of these biochemical pathways on the vascular tree is well established: the activation of sGC by NO promotes vasodilation and modulates vascular tone. Indeed, additional characteristics exist that lead physicians to believe there is a pleiotropic influence of this pathway on the functional activities and structural characteristics of human tissues and cells. Recently, sGC stimulators have demonstrated clinical efficacy in patients with worsening heart failure with reduced ejection fraction, improving cardiovascular death risk, re–hospitalization for HF, and all–cause mortality. These new outcome data have increased interest in understanding the potential pathophysiological mechanisms. The NO–sGC–cGMP axis may influence endothelial function, kidney performance, and cardiac muscle cell activity. The synergy of these actions could explain the positive effects of vericiguat on worsening HF. The aim of this narrative review was to provide a comprehensive insight into the pathophysiological mechanisms of action of NO–sGC–cGMP axis stimulators on cardiac muscle, endothelial cells, and kidneys.