Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model

Abstract

Arteriovenous (AV) fistula is the most common vascular access for hemodialysis in patients with end-stage renal disease. Studies have shown that blood flow in the AV fistula is significantly reduced in patients with diabetes and the period for maturation of an AV fistula is longer in these patients. The underlying mechanisms of AV fistula failure in diabetes are still poorly understood and there are limited therapeutic approaches that can increase the lifespan of these fistulas. The present study demonstrates that oral administration rosuvastatin improves blood flow and endothelial function of AC fistulas in rats with diabetes, which results from attenuating the activity of proinflammatory genes in the remodeled vasculature, thereby reducing the generation of tissue superoxide anions. Our results may thus enhance our ability to prevent and manage vascular access failure in patients with diabetes with chronic renal disease.

Rosuvastatin Suppresses the Oxidative Response in the Venous Limb of an Arteriovenous Fistula and Enhances the Fistula Blood Flow in Diabetic Rats

“…Since there was no previous control study investigating the vascular protective effect of statins on the AV fistulas of subjects with DM, we conducted a series of experimental studies testing the therapeutic potential of the water-soluble HMG-CoA reductase inhibitor rosuvastatin on the function of AV fistulas in diabetic rats. Our recent report demonstrated that rosuvastatin improves the blood flow and endothelial function of the arterial limb of the AV fistula in diabetic rats by attenuating the generation of tissue superoxide anions [11]. The current study extends the investigation of the protective effect of rosuvastatin from the arterial limbs to the venous sites of the AV fistula.…”

“…Animals underwent procedures to create a fistula in the aorta and adjacent inferior vena cava (IVC) to form an AV fistula as previously described in our reports [11,14]. Rats were anesthetized with inhaled isoflurane (2-3% v/v in oxygen).…”

“…The generation of superoxide anions in the blood vessels was measured using chemiluminescence and dihydroethidium assays as previously described [11,16]. In the chemiluminescence assay, venous tissues were immersed in Krebs-HEPES buffer solution for 30 min at 37°C and then transferred into the luminol-enhanced chemiluminescence chamber.…”

“…Administration of statins (HMG-CoA reductase inhibitors) shows beneficial effects on the reduction of vascular oxidative stress and improves endothelial functions in diabetic patients by increasing the bioavailability of endothelium-derived nitric oxide [7,8,9]. Although the protective effect of statins in the arterial tissue of subjects with hyperglycemia is well known [10,11], their vascular protective response in the venous tissue of AV fistulas has not been previously demonstrated. Besides, the molecular regulation of vascular remodeling in venous tissue following the creation of an AV fistula could be distinct from the changes at the arterial site, particularly in response to increased shear force, oxygen tension, and pressure.…”

O desenho da alça vascular arteriovenosa não interfere na sua patência: estudo experimental na pata de coelho

“…Encontram-se iniciativas de manter os vasos com a mesma conformação e avaliar os resultados de outros fatores, como drogas para inibir a proliferação da neo-íntima ( Aschberg et al 1976;Roan et al 2012). …”