Antioxidant diet and sex interact to regulate NOS isoform expression and glomerular mesangium proliferation in Zucker diabetic rat kidney.

Oxidative stress contributes substantially to the pathophysiology of diabetic nephropathy (DN). Consumption of an antioxidant-fortified (AO) diet from an early age prevents or delays later development of DN in the Zucker rat female with type 2 diabetes. We hypothesize this is due to effects on mesangial matrix and renal nitric oxide synthase (NOS) distribution and to sex-specific differences in NOS responses in the diabetic kidney.

L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway.

Rat studies demonstrated that type II diabetes mellitus (T2DM) decreases both the production and bioavailability of nitric oxide (NO). L-arginine (LA) provides the precursor for the production of NO. We hypothesized that LA dietary supplementation will preserve NO production via endothelial nitric oxide synthase (eNOS) causing renal microvascular vasodilation and increased glomerular blood flow and thus increasing glomerular filtration rate (GFR).

Antioxidant diet, gender and age affect renal expression of nitric oxide synthases in obese diabetic rats.

Development of diabetic nephropathy (DN) is associated with decreased renal nitric oxide production and increased oxidative stress. We studied nitric oxide synthase (NOS) expression in kidney of obese Zucker fa/fa rats, a model of Type 2 obesity-related DN. Male and female rats received a regular (REG) or antioxidant-fortified (AO) diet starting at age 4 weeks.

Protective effects of antioxidant-fortified diet on renal function and metabolic profile in obese Zucker rat.

Oxidative stress contributes to the pathophysiology of type 2 diabetes mellitus and its complications, including nephropathy. The current study was designed to test the hypothesis that a diet fortified with antioxidants would be beneficial to delay or prevent the progression of this disease. Male and female Zucker fa/fa rats were fed a control or an antioxidant (AO)-fortified diet starting at 4 weeks of age.

Enhanced acetylcholine-induced dilation in afferent arterioles in simvastatin-fed rats.

Objective: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to increase renal blood flow and glomerular filtration rate independent of their lipid lowering effects. The purpose of this study was to determine the effect of simvastatin on acetylcholine-induced vasodilation in the renal microcirculation. The hypothesis of the study was that simvastatin would increase acetylcholine-induced vasodilation in the renal microcirculation.

Simvastatin and L-arginine preserve renal function after ischemia/reperfusion injury.

Background: HMG-CoA reductase inhibitors have been shown to have beneficial renal hemodynamic effects by increasing renal blood flow, independent of their lipid-lowering properties. Currently in organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its use is limited by its nephrotoxic effects, namely its renal vasoconstrictor properties.

Renal tolerance to prolonged warm ischemia time in a laparoscopic versus open surgery porcine model.

Purpose: To our knowledge the effects of renal warm ischemia (WI) during laparoscopic vs open surgery have not been investigated. Decreased renal blood flow during pneumoperitoneum may precondition the kidney to tolerate longer WI time. Traditionally 30 minutes has defined the limit of renal WI time in open surgery.

Rapamycin preserves renal function compared with cyclosporine A after ischemia/reperfusion injury.

Objectives: To determine the effect of cyclosporine and rapamycin administration on renal function after ischemia/reperfusion injury (I/R). Cyclosporine A has known nephrotoxic effects. Thus, cyclosporine therapy subsequent to I/R injury may further exacerbate graft dysfunction.

Simvastatin attenuates renal ischemia/reperfusion injury in rats administered cyclosporine A.

Background: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors increase renal blood flow independent of their lipid-lowering properties. In organ transplantation, the calcineurin inhibitor cyclosporine A (CyA) is the immunosuppressant of choice. However, its renal vasoconstrictor properties limit its use.

Endothelin-receptor blockade mitigates the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats.

Background: Ischemia-reperfusion injury has been established as a nonimmunologic risk factor for the development of chronic graft nephropathy after renal transplantation. This objective of this study was to determine if oral administration of an endothelin-1 receptor (ET-R) antagonist over a 2-month period after renal transplantation would mitigate long-term dysfunction associated with 30 min of preretrieval warm ischemia (pre-WI).

Methods: The left kidney was retrieved from 250-g Lewis rats.

Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate.

Background: Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after transplantation (Tx).