The effects of acute lead exposure on renal function, lipid peroxidation and the expression of haeme oxygenase (HO) in rat kidney were determined. A single injection of lead acetate (50 mg Pb/kg) was given to rats. Changes in renal function, characterized by a significant reduction in the Na excretion was observed six hours after Pb exposure; this effect persisted for 24 hours. TBARS levels increased in kidney cortex 24 hours after Pb administration. In kidney cortex, Pb exposure affected the expression of HO-1, a renal protein associated with oxidative stress. HO-1 mRNA increased 2.3-fold, three hours after Pb administration and remained increased for six, 12 and 24 hours. HO enzymatic activity and HO-1 protein increased six and three hours after Pb administration, respectively, and remained increased at 24 hours. HO inhibition by tin-protoporphyrin, potentiated Pb-induced increase in TBARS and prevented the Pb-induced reduction in Na excretion. Our data suggest that Pb may be acting through the generation of oxidant products and induction of HO.
1 Differences in vascular responses to phenylephrine, acetylcholine (ACh) and potassium chloride (KCl) were studied in rabbit aorta from female and male rabbits, in the absence and presence of an inhibitor of nitric oxide (NO) production, N0-nitro-L-arginine methyl ester (L-NAME, 100 yM).2 Phenylephrine and KCl-induced contractions, were significantly reduced in amplitude (P<0.01) in the rings from female rabbits compared to those from male rabbits. 3 ACh-induced relaxation was greater (P<0.01) in aortic rings from females than from males. 4 Incubation of the rings with L-NAME abolished the phenylephrine-induced contraction differences between rings from male and female rabbits. 5 Ovariectomy eliminated the differences in vascular responses to phenylephrine, KCl and ACh of aortic rings from the female rabbits. 6 Both basal and ACh-stimulated release of nitrites from aortic rings was greater (P<0.01) in vascular tissue from female than male rabbits. 7 These results indicate that differences in vascular reactivity in aortic rings from male and female rabbits may be associated with a higher release of NO, resulting in an increased vasodilator response in the female rabbits.
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