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Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors.
Eur J Pharmacol 2008; 588(2-3):267-76EJ

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+Show Affiliations

Institute of Pharmacology and Therapeutics, Faculty of Medicine of Porto and IBMC, University of Porto, Porto, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18519134

Citation

Sousa, Teresa, et al. "Role of Superoxide and Hydrogen Peroxide in Hypertension Induced By an Antagonist of Adenosine Receptors." European Journal of Pharmacology, vol. 588, no. 2-3, 2008, pp. 267-76.
Sousa T, Pinho D, Morato M, et al. Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors. Eur J Pharmacol. 2008;588(2-3):267-76.
Sousa, T., Pinho, D., Morato, M., Marques-Lopes, J., Fernandes, E., Afonso, J., ... Albino-Teixeira, A. (2008). Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors. European Journal of Pharmacology, 588(2-3), pp. 267-76. doi:10.1016/j.ejphar.2008.04.044.
Sousa T, et al. Role of Superoxide and Hydrogen Peroxide in Hypertension Induced By an Antagonist of Adenosine Receptors. Eur J Pharmacol. 2008 Jul 7;588(2-3):267-76. PubMed PMID: 18519134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors. AU - Sousa,Teresa, AU - Pinho,Dora, AU - Morato,Manuela, AU - Marques-Lopes,José, AU - Fernandes,Eduarda, AU - Afonso,Joana, AU - Oliveira,Sofia, AU - Carvalho,Félix, AU - Albino-Teixeira,António, Y1 - 2008/04/24/ PY - 2007/11/05/received PY - 2008/04/02/revised PY - 2008/04/09/accepted PY - 2008/6/4/pubmed PY - 2008/9/3/medline PY - 2008/6/4/entrez SP - 267 EP - 76 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 588 IS - 2-3 N2 - 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18519134/Role_of_superoxide_and_hydrogen_peroxide_in_hypertension_induced_by_an_antagonist_of_adenosine_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00454-8 DB - PRIME DP - Unbound Medicine ER -