Vascular NADH/NADPH Oxidase Is Involved in Enhanced Superoxide Production in Spontaneously Hypertensive Rats
- 1 May 2000
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 35 (5), 1055-1061
- https://doi.org/10.1161/01.hyp.35.5.1055
Abstract
Abstract —This study was designed to test the hypothesis that stimulation of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase is involved in increased vascular superoxide anion (·O 2 − ) production in spontaneously hypertensive rats (SHR). The study was performed in 16-week-old and 30-week-old normotensive Wistar-Kyoto rats (WKY 16 and WKY 30 , respectively) and in 16-week-old and 30-week-old SHR (SHR 16 and SHR 30 , respectively). In addition, 16-week-old SHR were treated with oral irbesartan (average dose 20 mg/kg per day) for 14 weeks (SHR 30 -I). Aortic NADH/NADPH oxidase activity was determined by use of chemiluminescence with lucigenin. The expression of p22phox messenger RNA was assessed by competitive reverse transcription–polymerase chain reaction. Vascular responses to acetylcholine were determined by isometric tension studies. Aortic wall structure was studied, determining the media thickness and the cross-sectional area by morphometric analysis. Whereas systolic blood pressure was significantly increased in the 2 groups of hypertensive animals compared with their normotensive controls, no differences were observed in systolic blood pressure between SHR 30 and SHR 16 . No other differences in the parameters measured were found between WKY 16 and SHR 16 . In SHR 30 compared with WKY 30 , we found significantly greater p22phox mRNA level, NADH/NADPH-driven ·O 2 − production, media thickness, and cross-sectional area and an impaired vasodilation in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidase activity and p22phox expression as the WKY 30 group. The vascular functional and morphological parameters were improved in SHR 30 -I. These findings suggest that an association exists between p22phox gene overexpression and NADH/NADPH overactivity in the aortas of adult SHR. Enhanced NADH/NADPH oxidase–dependent ·O 2 − production may contribute to endothelial dysfunction and vascular hypertrophy in this genetic model of hypertension.Keywords
This publication has 19 references indexed in Scilit:
- Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats.JCI Insight, 1998
- p22 Is a Critical Component of the Superoxide-generating NADH/NADPH Oxidase System and Regulates Angiotensin IIinduced Hypertrophy in Vascular Smooth Muscle CellsPublished by Elsevier BV ,1996
- Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.JCI Insight, 1996
- Cytochrome b-558 α-subunit cloning and expression in rat aortic smooth muscle cellsBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1995
- Alterations in nitric oxide synthase activity, superoxide anion generation, and platelet aggregation in systemic hypertension, and effects of celiprololThe American Journal of Cardiology, 1994
- EFFECT OF DELAPRIL ON THE VASCULAR ANGIOTENSIN II RELEASE IN ISOLATED HIND LEGS OF THE SPONTANEOUSLY HYPERTENSIVE RAT: EVIDENCE FOR POTENTIAL RELEVANCE OF VASCULAR ANGIOTENSIN II TO THE MAINTENANCE OF HYPERTENSIONClinical and Experimental Pharmacology and Physiology, 1991
- Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition.Hypertension, 1991
- Age-related variations in tissue angiotensin converting enzyme activities: comparison between spontaneously hypertensive and Wistar-Kyoto ratsJournal Of Hypertension, 1990
- Atrial natriuretic factor prevents NaCl-sensitive hypertension in spontaneously hypertensive rats.Hypertension, 1990
- The glycoprotein encoded by the X-linked chronic granulomatous disease locus is a component of the neutrophil cytochrome b complexNature, 1987