ИСТИНА

Introduction and Aims: Renal blood flow abnormalities play an important role in the pathogenesis of ischemic acute kidney injury (AKI). During ischemia the oxidative stress and mitochondrial dysfunction are the major steps of kidney damage, and mitochondria-targeted antioxidants are considered to be a perspective approach of AKI treatment. In this work we investigated the renal and central hemodynamics by high-frequency ultrasound Doppler technique. Methods: We used high-frequency ultrasound Doppler technology (27 MHz). Measurement of blood flow was carried out by bandage type sensors with an internal diameter of 1.5-2 mm. Experiments were performed on 350-450 g male rats. Doppler sensors were applied on the renal artery and the abdominal part of the aorta, proximal to the renal arteries. After stabilization of blood flow left kidney renal artery was clamped for 40 min. During the experiment we carried out registration of linear and volumetric blood flow velocity. Results: We found that after 40-min ischemia the renal blood flow during reperfusion period was restored to no more than 40% of the normal values and renal vascular resistance increased by more than 20%. Monitoring of linear and average velocity of blood flow in the abdominal aorta, and heart rate measurement showed that I/R of kidneys do not lead to significant changes in central hemodynamics. Injection of mitochondria-targeted antioxidant SkQR1 3 hours before ischemia resulted in an increased renal blood flow (about 67% of the pre-ischemic values) and normalized vascular renal resistance in early reperfusion period. Administration of NO-synthase inhibitor Nω-L-nitroarginine along with SkQR1 abolished the positive effect of the antioxidant. Conclusions: The mechanism of positive effect of mitochondria-targeted antioxidant SkQR1 on renal hemodynamics may be associated with reduction of ROS production in the vessel wall and, consequently, increased bioavailability of NO, which readily reacts with the superoxide radical. Thus, the protective effect of SkQR1 may be concerned with lower severity of secondary hypoxia caused by impaired renal bloodflow after I/R.