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Oxidative Stress in a Rat Model of Obesity-Induced Hypertension
Abstract
The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity. When Sprague-Dawley rats (n=60) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (158±3.4 mm Hg systolic pressure), whereas the other half (obesity-resistant [OR] group) maintains a body weight equivalent to that of a low fat control group and is normotensive (135.8±3.8 mm Hg). We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid–reactive substances showed a significant increase in the LDL fraction of OP rats (2.8±0.32 nmol malondialdehyde/mg protein) compared with OR and control rats (0.9±0.3 nmol malondialdehyde/mg protein). Also, aortic and kidney thiobarbituric acid–reactive substances showed a significant (3- and 5- fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold increase in the OP group compared with both the OR and control groups. In addition, free isoprostane excretion and nitrotyrosine in the kidney showed an increase in OP rats only. The urine and plasma nitrate/nitrite measured by the LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However, endothelial NO synthase expression in the kidney cortex and medulla assessed by reverse transcriptase–polymerase chain reaction showed a strong increase in the OP rats versus OR and control rats (endothelial NO synthase/β-actin ratio 1.3±0.04 in OP rats versus 0.44±0.02 in OR rats), suggesting a possible shift toward superoxide production by the enzyme. Collectively, the data show a decreased NO bioavailability in OP animals that is due in part to the increased oxidative stress.
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Cites
The formation of peroxynitrite in vivo from nitric oxide and superoxide
Squadrito, G. L., & Pryor, W. A. (1995) · Chemico-Biological Interactions · doi:10.1016/0009-2797(94)03591-u · Cited by 200
Cited by
Reactive oxygen species in vascular biology: implications in hypertension
Touyz, R. M., & Schiffrin, E. L. (2004) · Histochemistry and Cell Biology · doi:10.1007/s00418-004-0696-7 · Cited by 646
Platelet Activation in Obese Women: Role of Inflammation and Oxidant Stress
Davì, G., Guagnano, M. T., Ciabattoni, G., Basili, S., Falco, A., Marinopiccoli, M., Nutini, M., Sensi, S., & Patrono, C. (2002) · JAMA · doi:10.1001/jama.288.16.2008 · Cited by 541
Obesity, Sleep Apnea, and Hypertension
Wolk, R., Shamsuzzaman, A. S. M., & Somers, V. K. (2003) · Hypertension · doi:10.1161/01.hyp.0000101686.98973.a3 · Cited by 532
Antioxidant Activities and Oxidative Stress Byproducts in Human Hypertension
Redón, J., Oliva, M. R., Tormos, C., Giner, V., Chaves, J., Iradi, A., & Sáez, G. T. (2003) · Hypertension · doi:10.1161/01.hyp.0000068370.21009.38 · Cited by 420
Boustany, C. M., Bharadwaj, K., Daugherty, A., Brown, D. R., Randall, D. C., & Cassis, L. A. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00265.2004 · Cited by 337
Metadata
- Authors
- Dobrian, A. D., Davies, M. J., Schriver, S. D., Lauterio, T. J., & Prewitt, R. L.
- Venue
- Hypertension
- Published
- 2001-02
- Volume
- 37
- Issue
- 2
- Pages
- 554-560
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2098814645
- Cited by
- 246
- References
- 1
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- closed
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