Riosiguat ön tedavisinin sıçan böbrek iskemi-reperfüzyon modelinde renal fonksiyonlara etkisi
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Date
2024Author
ALTINIŞIK, Yaşar Can
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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. Ischemiareperfusion 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.