Intrarenal artery superoxide is mainly NADPH oxidase-derived and modulates endothelium-dependent dilation in elderly patients

Aims The present study was performed to investigate the contribution of NADPH oxidases (Nox) to superoxide formation in human renal proximal resistance arteries and to test whether superoxide formation contributes to acute vasoconstrictor responses and endothelium-dependent vasodilation in these vessels. Methods and results Arcuate and proximal interlobular artery segments were from patients who underwent nephrectomy because of a renal tumour. Vessels were dissected from tumour-free parts of the kidneys. Additional intrarenal arteries were obtained from rats. Superoxide formation was measured by lucigenin-enhanced chemiluminescence, expression of Nox isoforms was analysed by RT–PCR, and functional studies were performed by small vessel wire myography. Sixty per cent of superoxide formation in human arcuate and proximal interlobular arteries was due to Nox activity. mRNA expression analyses revealed the presence of Nox2 and Nox4 but not Nox1. Phenylephrine and endothelin-1 induced powerful concentration-dependent vasoconstrictions that were unaffected by superoxide scavengers. Vasopressin elicited small and variable vasoconstrictions with signs of tachyphylaxis. Endothelium-dependent vasodilation was blunted by tiron and N ω-nitro-l-arginine methyl ester but not by superoxide dismutase or catalase. Exogenous hydrogen peroxide elicited vasoconstriction. Conclusion Nox activity is the major source of superoxide formation in renal proximal resistance arteries from elderly patients. Acute vasoconstrictor responses to α1-adrenoreceptor activation and to endothelin-1 do not depend on superoxide formation, while endothelium-dependent vasodilation in intrarenal arteries is reactive oxygen species-dependent.