Vericiguat prevents hepatic inflammation and microcirculatory dysfunction in the early phase of sepsis in mice.

Sepsis remains a major cause of morbidity and mortality worldwide, with persistent microcirculatory dysfunction driving progressive organ injury despite optimal macrocirculatory support. Vericiguat, a soluble guanylate cyclase (sGC) stimulator approved for chronic heart failure, enhances nitric oxide signaling, promoting vasodilation and supporting endothelial integrity. Based on this profile of action, we hypothesized that vericiguat improves hepatic microcirculatory perfusion in sepsis and thereby mitigates liver injury. Male C57BL/6J mice underwent sham surgery (n = 8) or cecal ligation and puncture (CLP). CLP-treated mice received either vericiguat (3 mg/kg body weight; n = 8) or dimethyl sulfoxide (DMSO) 50% as vehicle control (n = 8). Six hours later, the livers were examined by means of intravital fluorescence microscopy, followed by immunohistochemical and plasma analyses. Vericiguat significantly reduced leukocyte-endothelial cell interactions and macromolecular leakage in the microcirculation of septic livers. Moreover, it reduced sinusoidal perfusion failure and normalized the expression of the extracellular matrix marker perlecan. Plasma analyses did not reveal marked differences between vericiguat- and vehicle-treated septic mice, most probably due to the early observation time point after CLP. Taken together, these findings suggest that vericiguat may represent a promising drug in sepsis, potentially preventing early hepatic inflammation and microcirculatory dysfunction.