Oxidative stress in a rat model of obesity-induced hypertension

The mechanisms underlying the development of hypertension in obesity are no t yet fully understood. We recently reported the development of hypertensio n in a rat model of diet-induced obesity. When Sprague-Dawley rats (n=60) a re fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approx imately half of them develop obesity (obesity-prone [OP] group) and mild hy pertension (158+/-3.4 mmHg systolic pressure), whereas the other half (obes ity-resistant [OR] group) maintains a body weight equivalent to that of a l ow fat control group and is normotensive (135.8+/-3.8 mm Hg). We examined t he potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid-reactive subst ances 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 thiobarbit uric acid-reactive substances showed a significant (3- and 5-fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by a ortic rings, measured by lucigenin luminescence, showed a 2-fold increase i n the OP group compared with both the OR and control groups. In addition. f ree isoprostane excretion and nitrotyrosine in the kidney showed an increas e 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. Howeve r, endothelial NO synthase expression in the kidney cortex and medulla asse ssed by reverse transcriptase-polymerase chain reaction showed a strong inc rease in the OP rats versus OR and control rats (endothelial NO synthase/be ta -actin ratio 1.3+/-0.04 in OP rats versus 0.44+/-0.02 in OR rats), sugge sting a possible shift toward superoxide production by the enzyme. Collecti vely, the data show a decreased NO bioavailability in OP animals that is du e in part to the increased oxidative stress.