NAD(P)H oxidase inhibition improves endothelial function in rat and human blood vessels

Hamilton, C., Brosnan, M., Al Benna, S., Berg, G. and Dominiczak, A. (2002) NAD(P)H oxidase inhibition improves endothelial function in rat and human blood vessels. Hypertension, 40(5), pp. 755-762. (doi: 10.1161/01.HYP.0000037063.90643.0B)

Abstract

The NO/superoxide (O2−) balance is a key regulator of endothelial function. O2− levels are elevated in many forms of cardiovascular disease; therefore, decreasing O2− should improve endothelial function. To explore this hypothesis, internal mammary arteries and saphenous veins, obtained from patients undergoing coronary artery revascularization, and aortic and carotid arteries from Wistar-Kyoto and spontaneously hypertensive stroke-prone rats were incubated with O2− dismutase or NAD(P)H oxidase inhibitors. O2− levels were measured using lucigenin chemiluminescence; NO bioavailability was assessed in organ chambers; and mRNA expression of NAD(P)H oxidase components was quantified by use of a Light Cycler. In rat arteries, phenylarsine oxide, 4-(2-aminoethyl)-benzenesulfanyl fluoride, and apocynin all decreased NADH-stimulated O2− production, but only apocynin increased NO bioavailability. In human internal mammary arteries and saphenous veins, apocynin decreased NAD(P)H-stimulated O2− generation and caused vasorelaxation that was endothelium dependent and reversed on addition of the NO synthase inhibitor NG-nitro-l-arginine methyl ester. In addition, it increased NO production from cultured human endothelial saphenous vein cells. Polyethylene-glycolated O2− dismutase also increased NO bioavailability in rat carotid arteries and human blood vessels, but the effects were smaller than those observed with apocynin. NADH-generated O2− and mRNA expression of p22phox, gp91phox, and nox-1 were comparable between the 2 strains of rat. This is the first study to demonstrate pharmacological effects of apocynin in human blood vessels. The increases in NO bioavailability shown here suggest that the NAD(P)H oxidase pathway may be a novel target for drug intervention in cardiovascular disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hamilton, Dr Carlene and Dominiczak, Professor Anna
• Authors: Hamilton, C., Brosnan, M., Al Benna, S., Berg, G., and Dominiczak, A.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X