Effect of riociguat pretreatment on renal functions in rat kidney ischemia- reperfusion model

Ischemia-reperfusion (I-R) injury is a pathological condition that can affect many organs in the body. Ischemia-reperfusion damage, especially in the kidney, directly causes intrarenal vascular damage by facilitating the development of acute kidney injury and significantly increasing mortality. The nitric oxide (NO) / soluble guanylate cyclase (sGC) / cyclic guanosine monophosphate (cGMP) pathway has a protective effect on the vascular system. Riociguat, a soluble guanylate cyclase stimulator, is approved for use in the treatment of pulmonary arterial hypertension. Due to its beneficial effects on the vascular system, the effects of this drug on other systems and diseases are widely investigated. Studies have shown that riociguat has an anti-inflammatory effects and has also shown that it has direct protective effects on the lungs, heart and kidneys. In this study, the effect of riociguat pretreatment on physiological and renal functions in acute kidney injury in a rat renal ischemia-reperfusion injury model was examined. Riociguat pretreatment reversed the decreased renal artery blood flow and impaired renal tissue perfusion as a result of renal ischemia-reperfusion in the kidney. Functional responses of the renal vascular bed to vasoconstricting and vasodilating agents were evaluated in the isolated perfused kidney setup. Ischemia-reperfusion injury significantly reduced acetylcholine and sodium nitroprusside induced relaxation responses, whereas riociguat pretreatment increased the impaired relaxation responses. No significant differences were found in the contractile responses produced by angiotensin II and phenylephrine. Deteriorated renal histopathology after renal ischemia reperfusion injury showed a tendency to improve with riociguat pretreatment. In ELISA experiments, no significant differences were found in interleukin-1β levels. Riociguat pretreatment significantly increased levels of IL-10 which is an anti-inflammatory cytokine. These results paved the way for future clinical studies to use riociguat as a preventive treatment in patients at risk of developing AKI due to I-R injury.