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

Abstract

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 (O2.-) vs hydrogen peroxide (H2O2). Vascular and systemic prooxidant/antioxidant status was evaluated in sham (saline, i.p., 7 days) and DPSPX (90 microg/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/spectrophotometric 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 apocynin (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 O2.- generation with subsequent formation of H2O2 plays a major role in the development of DPSPX-induced hypertension.

• Authors: Teresa Sousa, Dora Pinho, Manuela Morato, José Marques-Lopes, Eduarda Fernandes, Joana Afonso, Sofia Oliveira, Félix Carvalho, António Albino-Teixeira
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 588 Issue 2-3 Pg. 267-76 (Jul 07 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18519134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Purinergic P1 Receptor Antagonists
• Xanthines
• catalase-polyethylene glycol
• Superoxides
• Polyethylene Glycols
• 1,3-dipropyl-8-(4-sulfophenyl)xanthine
• acetovanillone
• Hydrogen Peroxide
• Catalase
• Superoxide Dismutase
• NADPH Oxidases

Topics

• Acetophenones (pharmacology)
• Animals
• Blood Vessels (drug effects, pathology)
• Catalase (pharmacology)
• Hydrogen Peroxide (metabolism)
• Hypertension (chemically induced)
• Lipid Peroxidation (drug effects)
• Male
• NADPH Oxidases (metabolism)
• Polyethylene Glycols (pharmacology)
• Purinergic P1 Receptor Antagonists
• Rats
• Rats, Wistar
• Superoxide Dismutase (metabolism)
• Superoxides (metabolism)
• Systole (drug effects)
• Xanthines (pharmacology)