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Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension.
Kidney Int. 2003 Jan; 63(1):186-94.KI

Abstract

BACKGROUND

Earlier studies from this laboratory have revealed the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension (HTN). We have further shown evidence of increased hydroxyl radical (.OH) and superoxide production in lead-treated rats and cultured endothelial cells. This study was designed to determine whether oxidative stress in animals with lead-induced HTN is associated with dysregulation of the main antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) or increased superoxide producing enzyme nicotinamide adenine dinucleotide (phosphate) oxidase [NAD(P)H].

METHODS

Male Sprague-Dawley rats were randomly assigned to lead-exposed and control groups. Animals in the lead-exposed group were provided with drinking water containing 100 ppm lead acetate for 12 weeks. The control group was provided with regular drinking water. At the conclusion of the experiment, immunodetectable Cu Zn SOD, Mn SOD, CAT, GPX and gp91 phox subunit of NAD(P)H oxidase were determined by Western analysis in the kidney, brain and left ventricle of control and lead-exposed rats. Subgroups of the study animals were treated with IV infusion (180 micromol/kg/h) of the superoxide trapping agent, tempol, and arterial pressure and urinary nitric oxide (NO) metabolite (NOx) excretion were determined.

RESULTS

Lead exposure for 12 weeks resulted in a marked rise in systolic blood pressure, a significant reduction in urinary NOx excretion, a significant increase in kidney and brain Cu, Zn SOD, a significant increase in brain and insignificant increase in kidney and heart gp91 phox. In contrast, Mn SOD, CAT and GPX in the kidney, brain and left ventricle were unchanged. Incubation with lead acetate did not alter SOD activity in vitro. Infusion of tempol significantly lowered arterial pressure and raised urinary NOx excretion in the lead-exposed group (but had no effect in the control group) pointing to increased superoxide production in the lead-exposed animals.

CONCLUSION

Animals with lead-induced hypertension exhibited oxidative stress which was associated with mild up-regulation of superoxide-generating enzyme, NAD(P)H oxidase, with no evidence of quantitative SOD, CAT or GPX deficiencies.

Authors+Show Affiliations

Departments of Medicine, Physiology and Biophysics University of California, Irvine, Irvine, California, USA. ndvaziri@uci.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12472782

Citation

Vaziri, Nosratola D., et al. "Superoxide Dismutase, Catalase, Glutathione Peroxidase and NADPH Oxidase in Lead-induced Hypertension." Kidney International, vol. 63, no. 1, 2003, pp. 186-94.
Vaziri ND, Lin CY, Farmand F, et al. Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension. Kidney Int. 2003;63(1):186-94.
Vaziri, N. D., Lin, C. Y., Farmand, F., & Sindhu, R. K. (2003). Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension. Kidney International, 63(1), 186-94.
Vaziri ND, et al. Superoxide Dismutase, Catalase, Glutathione Peroxidase and NADPH Oxidase in Lead-induced Hypertension. Kidney Int. 2003;63(1):186-94. PubMed PMID: 12472782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension. AU - Vaziri,Nosratola D, AU - Lin,Ching-Yi, AU - Farmand,Farbod, AU - Sindhu,Ram K, PY - 2002/12/11/pubmed PY - 2004/3/3/medline PY - 2002/12/11/entrez SP - 186 EP - 94 JF - Kidney international JO - Kidney Int VL - 63 IS - 1 N2 - BACKGROUND: Earlier studies from this laboratory have revealed the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension (HTN). We have further shown evidence of increased hydroxyl radical (.OH) and superoxide production in lead-treated rats and cultured endothelial cells. This study was designed to determine whether oxidative stress in animals with lead-induced HTN is associated with dysregulation of the main antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) or increased superoxide producing enzyme nicotinamide adenine dinucleotide (phosphate) oxidase [NAD(P)H]. METHODS: Male Sprague-Dawley rats were randomly assigned to lead-exposed and control groups. Animals in the lead-exposed group were provided with drinking water containing 100 ppm lead acetate for 12 weeks. The control group was provided with regular drinking water. At the conclusion of the experiment, immunodetectable Cu Zn SOD, Mn SOD, CAT, GPX and gp91 phox subunit of NAD(P)H oxidase were determined by Western analysis in the kidney, brain and left ventricle of control and lead-exposed rats. Subgroups of the study animals were treated with IV infusion (180 micromol/kg/h) of the superoxide trapping agent, tempol, and arterial pressure and urinary nitric oxide (NO) metabolite (NOx) excretion were determined. RESULTS: Lead exposure for 12 weeks resulted in a marked rise in systolic blood pressure, a significant reduction in urinary NOx excretion, a significant increase in kidney and brain Cu, Zn SOD, a significant increase in brain and insignificant increase in kidney and heart gp91 phox. In contrast, Mn SOD, CAT and GPX in the kidney, brain and left ventricle were unchanged. Incubation with lead acetate did not alter SOD activity in vitro. Infusion of tempol significantly lowered arterial pressure and raised urinary NOx excretion in the lead-exposed group (but had no effect in the control group) pointing to increased superoxide production in the lead-exposed animals. CONCLUSION: Animals with lead-induced hypertension exhibited oxidative stress which was associated with mild up-regulation of superoxide-generating enzyme, NAD(P)H oxidase, with no evidence of quantitative SOD, CAT or GPX deficiencies. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/12472782/Superoxide_dismutase_catalase_glutathione_peroxidase_and_NADPH_oxidase_in_lead_induced_hypertension_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)48858-1 DB - PRIME DP - Unbound Medicine ER -