Nephrol Dial Transplant (2001) 16: 2-5
© 2001 European Renal Association-European Dialysis and Transplant Association
Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction?
Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, Pamplona, Spain
Background. Increases in oxidant stress, i.e. excessive production of superoxide anion (
), have been reported in different models of hypertension. This study was designed to test the hypothesis that increased production, more than diminished nitric oxide (NO) generation, plays a critical role in endothelial dysfunction present in spontaneously hypertensive rats (SHR).
Methods. The study was performed in 30-week-old normotensive Wistar–Kyoto rats (WKY) and SHR. In addition, 16-week-old SHR were treated with oral irbesartan (average dose 20 mg/kg per day) for 14 weeks (SHR-I). Aortic nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity was determined by use of chemiluminescence with lucigenin. Aortic constitutive nitric oxide synthase (cNOS) activity was determined by measuring the conversion of L-arginine to L-citrulline. Vascular responses to acetylcholine were determined by isometric tension studies.
Results. Whereas systolic blood pressure (SBP) was significantly increased in SHR compared with WKY, no differences were observed in SBP between SHR-I and WKY. In SHR compared with WKY, we found significantly greater NADH/NADPH-driven production, similar cNOS-mediated NO production and an impaired vasodilation in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidase activity and significantly lower cNOS activity than the WKY group. Vasodilation in response to acetylcholine was improved in SHR-I.
Conclusions. These findings suggest that a diminished availability of NO secondary to an enhanced NADH/NADPH oxidase-dependent production may play a critical role in endothelial dysfunction of adult SHR.
Keywords: endothelium; hypertension; nitric oxide; superoxide
Correspondence and offprint requests to: Javier Díez, MD, PhD, División de Fisiopatología Cardiovascular, Facultad de Medicina, C/Irunlarrea s/n, 31080 Pamplona, Spain.
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