Effects of nitric oxide synthase inhibition and L-arginine on renal haemodynamics in young patients at high cardiovascular risk.

Background: Aging and a variety of cardiovascular risk factors are associated with oxidative stress and impaired endothelial function. Whether such an association is already evident in the renal vascular bed in young patients at high cardiovascular risk has not yet been determined.

Methods: We compared renal haemodynamics in 23 young (age 30+/-5 years) male patients at high cardiovascular risk with impaired lipid metabolism and elevated blood pressure with 23 matched, healthy control subjects (age 28+/-3 years) without cardiovascular risk factors at baseline and following infusions of the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA: 4.25mg/kg), the substrate of NO synthase L-arginine (100mg/kg) and the antioxidant Vitamin C (3g, co-infused with L-arginine 100mg/kg).

Results: Baseline renal haemodynamics did not differ between the two groups. Infusion of L-NMMA decreased renal plasma flow (RPF) in both groups to a similar extent (-113+/-95 ml/min versus -128+/-133 ml/min, p=NS). The response of RPF to infusion of L-arginine was more pronounced in high risk patients than in control subjects (+123+/-64.4 ml/min versus +75.6+/-60.2 ml/min, p=0.012) and further exaggerated during co-infusion of L-arginine and Vitamin C (+299+/-164 ml/min versus +175+/-148 ml/min, p=0.003).

Conclusions: Basal NO activity of the renal vasculature appears to be unaltered in young patients at high cardiovascular risk. However, the greater response of RPF to L-arginine and to Vitamin C co-infused with L-arginine in these young patients suggests that decreased substrate availability for NO synthase and oxidative stress are key factors for alterations in endothelium-dependent vasodilation of the renal vasculature in this young high risk group of patients.