Possible prooxidant effect of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1) antagonists in neural tissue
Abstract
Angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT1) antagonists (ARBs, sartans) are widely used for treatment of cardiovascular diseases. Many findings suggest they also have a potent ability to protect tissues against the damage associated with oxidative stress.
Contrary to these results, our experiments show ACE inhibitors and sartans may have some prooxidant activity, mainly in neural tissue. Male Wistar rats were treated orally once daily for 3 days with captoril (50 mg/kg), losartan (20 mg/kg), or telmisartan (10 mg/kg).
All substances were given by gastric gavages, dispersed in methylcellulose. Animals in the control group received methylcellulose only.
On the fourth day, parameters of oxidative state: lipid peroxidation (thiobarbituric acid reactive substances), reduced glutathione (GSH) and activity of antioxidant enzymes glutathione peroxidase and glutathione reductase were estimated in liver and brain homogenates. Administration of captopril as well as losartan and telmisartan significantly increased lipid peroxidation in brain tissue (P < 0.01).
There were no significant changes of brain GSH content or glutathione peroxidase and glutathione reductase activities. Losartan decreased the activity of glutathione peroxidase (P < 0.01) and both losartan and telmisartan decreased glutathione reductase activity (P < 0.001; P < 0.05) in liver tissue.
There were no significant changes in liver lipid peroxidation after administration of captopril or any of the AT1 receptor blockers. Telmisartan slightly increased the content of liver glutathione (P < 0.05) and the activity of glutathione peroxidase in the brain (P < 0.05), however neither captopril nor losartan had such effect.
The ability of ACE inhibitors or AT1 receptor blockers to increase lipid peroxidation in brain after short term oral administration has not been described in the literature yet and further studies could be useful.