Gender is related to alterations of renal endothelial function in type 2 diabetes

Abstract

Gender has been shown to affect endothelial function of the forearm circulation in patients with type 2 diabetes, but data on the renal circulation are lacking. We hypothesized that renal vascular nitric oxide (NO) availability is higher, and oxidative stress lower, in female compared to male patients with type 2 diabetes. In 41 male and 39 female patients with type 2 diabetes, renal plasma flow (RPF) was determined by constant infusion input clearance at baseline and following infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4.25 mg/kg) to assess basal renal vascular NO availability. After a subsequent infusion of L-arginine (100 mg/kg) to restore baseline conditions, vitamin C (45 mg/kg) was co-infused to determine levels of oxidative stress in the renal circulation. Baseline renal haemodynamics were similar between genders. L-NMMA-induced renal vasoconstriction was more pronounced in females compared to males (-89 +/- 69 versus -60 +/- 52 ml/min/1.73 m(2), P = 0.03). After administration of L-arginine to restore baseline perfusion, the co-infusion of vitamin C led to a lesser increase of RPF in females than in males (+37 +/- 86 versus +60 +/- 52 ml/min/1.73 m(2), P = 0.05). Our data demonstrate that NO availability in the renal circulation is greater in female than in male patients with type 2 diabetes that is associated with reduced levels of oxidative stress in females. The role of this gender-related difference in renal endothelial function for the initiation and progression of diabetic nephropathy should be addressed in future studies.