Hydralazine, but not Captopril, Decreases Free Radical Production and Apoptosis in Neurons and Thymocytes

The effects of captopril and hydralazine, two commonly used antihypertensive drugs, on free radical generation and the onset of apoptosis in neuron and thymocyte preparations from 10-12 day old rats have been studied. Apoptosis was induced in neurons by kainate or N-methyl-D-aspartate and in thymocytes by heat shock. Intracellular free radical production was measured by 2',7'-dichlorofluorescein fluorescence, and apoptotic cells were detected by cell staining with fluorescein-labelled annexin V. Captopril was found to have no effect on intracellular free radical generation and also had no significant effect on the early stages of apoptosis in neurons and thymocytes. In contrast, hydralazine was found to decrease free radical generation in both neurons and thymocytes, and it also significantly decreased the numbers of apoptotic cells when neurons and thymocytes were stimulated for apoptosis. Hydralazine had a greater effect on decreasing free radical generation in neurons than in thymocytes, but it had a more pronounced effect on decreasing apoptosis in thymocytes compared to neurons, suggesting that apoptosis, under our experimental conditions, may not solely be triggered by free radical generation. These results contrast with earlier reports that captopril is a free radical scavenger and can decrease apoptosis in T-lymphocytes and cardiomyocytes, and the results obtained with hydralazine are in apparent disagreement with earlier reports that this drug is a free radical generator and can cause intracellular damage suggestive of enhanced free radical formation.