Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Teresa Sousa (Author) FFUP; Dora Pinho (Author) FCNAUP; Manuela Morato (Author) FFUP; Jose Marques Lopes (Author) Other; Eduarda Fernandes (Author) FFUP; Joana Afonso (Author) Other; Sofia Oliveira (Author) Other; Felix Carvalho (Author) FFUP; Antonio Albino Teixeira (Author) FMUP

Journal

Title: European Journal of Pharmacology

Vol. 588

Pages: 267-276

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 40 Citations

Scopus - 40 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-XT6

DOI: 10.1016/j.ejphar.2008.04.044

Abstract (EN): Treatment of Wistar rats for 7 days with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, induces long-lasting hypertension associated with marked changes in vascular structure and reactivity and renin-angiotensin system activation. This study aimed at evaluating the role of oxidative stress in the development of DPSPX-induced hypertension and also at identifying the relative contribution of superoxide radical (O-2(center dot-)) vs hydrogen peroxide (H2O2). Vascular and systemic prooxidant/antioxidant status was evaluated in sham (saline, i.p., 7 days) and DPSPX (90 mu g/kg/h, i.p., 7 days)-treated rats. Systolic blood pressure was determined by invasive and non-invasive methods. The activity of vascular NADPH oxidase, superoxide dismutase (SOD), catalase and glutathione peroxidase was assayed by fluorometric/spectro-photometric methods. H2O2 levels were measured using an Amplex Red Hydrogen Peroxide kit. Plasma thiobarbituric acid reactive substances and plasma antioxidant capacity were also measured. In addition we tested the effects of antioxidants or inhibitors of reactive oxygen species generation on blood pressure, vascular hyperplasia and oxidative stress parameters. DPSPX-hypertensive rats showed increased activity of vascular NADPH oxidase, SOD, catalase and glutathione peroxidase, as well as increased H2O2 generation. DPSPX-hypertensive rats also had increased plasma lipid peroxidation and decreased plasma antioxidant capacity. Treatment with apocypin (1.5 mmol/l, per os, 14 days), or with polyethylene glycol (PEG)-catalase (10,000 U/kg/day, i.p., 8 days), prevented the DPSPX-induced effects on blood pressure, vascular structure and H2O2 levels. Tempol (3 mmol/l, per os, 14 days) failed to inhibit these changes, unless PEG-catalase was co-administered. It is concluded that O-2(center dot-) generation with subsequent formation of H2O2 plays a major role in the development of DPSPX-induced hypertension.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10