Journal article
Chronic aldosterone administration causes Nox2-mediated increases in reactive oxygen species production and endothelial dysfunction in the cerebral circulation
Journal of hypertension, Vol.32(9), pp.1815-1821
09/01/2014
DOI: 10.1097/HJH.0000000000000259
PMCID: PMC4151299
PMID: 24991871
Abstract
Objectives: An elevated plasma aldosterone level is an independent cardiovascular risk factor. Although excess aldosterone promotes cardiovascular disease, no studies have examined the effect of increased plasma aldosterone on the cerebral circulation. A major source of vascular reactive oxygen species (ROS) during cardiovascular disease is the NADPH oxidases. Because Nox2-containing NADPH oxidase (Nox2 oxidase) is highly expressed in the cerebral endothelium, we postulated that it might contribute to ROS generation and vascular dysfunction in response to aldosterone. Here, we examined the effect of aldosterone and Nox2 oxidase on ROS production and endothelial dysfunction in the cerebral circulation, and whether the effects of aldosterone are exacerbated in aged mice.
Methods and results: In adult (average age similar to 24-25 weeks) wild-type and Nox2-deficient (Nox2(-/y)) mice, neither vehicle nor aldosterone (0.28 mg/kg per day for 14 days) affected blood pressure (measured using tail-cuff). By contrast, aldosterone treatment reduced dilation of the basilar artery (measured using myography) to the endothelium-dependent agonist acetylcholine in wild-type mice (P < 0.05), but had no such effect in Nox2(-/y) mice (P > 0.05). Aldosterone increased basal and phorbol dibutyrate-stimulated superoxide production (measured using L-012-enhanced chemiluminesence) in cerebral arteries from wild-type but not from Nox2(-/y) mice. In aged wild-type mice (average age similar to 70 weeks), aldosterone treatment increased blood pressure, but had a similar effect on cerebral artery superoxide levels as in adult wild-type mice.
Conclusion: These data indicate that Nox2 oxidase mediates aldosterone-induced increases in ROS production and endothelial dysfunction in cerebral arteries from adult mice independently of blood pressure changes. Aldosterone-induced hypertension is augmented during aging.
Details
- Title: Subtitle
- Chronic aldosterone administration causes Nox2-mediated increases in reactive oxygen species production and endothelial dysfunction in the cerebral circulation
- Creators
- Sophocles Chrissobolis - Roy J. and Lucille A. Carver College of MedicineGrant R. Drummond - Monash Univ, Dept Pharmacol, Vasc Biol & Immunopharmacol Grp, Clayton, Vic 3800, AustraliaFrank M. Faraci - University of IowaChristopher G. Sobey - Monash Univ, Dept Pharmacol, Vasc Biol & Immunopharmacol Grp, Clayton, Vic 3800, Australia
- Resource Type
- Journal article
- Publication Details
- Journal of hypertension, Vol.32(9), pp.1815-1821
- DOI
- 10.1097/HJH.0000000000000259
- PMID
- 24991871
- PMCID
- PMC4151299
- NLM abbreviation
- J Hypertens
- ISSN
- 0263-6352
- eISSN
- 1473-5598
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Grant note
- High Blood Pressure Research Council of Australia R01HL113863; P01HL062984 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) BX001399 / Department of Veterans Affairs; US Department of Veterans Affairs NS-24621; HL-62984; HL-113863 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA G 10M 5218 / National Heart Foundation of Australia P01NS024621 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 359282 / National Health and Medical Research Council (NHMRC) of Australia I01BX001399 / Veterans Affairs; US Department of Veterans Affairs
- Language
- English
- Date published
- 09/01/2014
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984303854902771
Metrics
3 Record Views