Activated neutrophils which produce certain proteases, such as elastase and reactive oxygen species (ROS) are involved in oxidative stress and inflammation. In the present study, we have shown that nicardipine, a calcium channel blocker, affects the release of elastase and superoxide anion radicals (O(2-)) in vitro during human and rabbit neutrophil respiratory bursts. The drug inhibited the release of elastase and O(2-) by fMLP (N-formyl-methionylleucin-phenylalaninin), calcium ionophore (A23187) and PMA (phorbol-myristate-acetate)-stimulated human and rabbit neutrophils. Besides the release of elastase, strongly inhibited in the fMLP and A23187 stimulated systems, nicardipine affected elastase and O(2-) in a dose-dependent manner. The corresponding 50% inhibitory concentration (IC(50)) of nicardipine for elastase, released in PMA-stimulated human and rabbit neutrophils, was 15.95 +/- 0.17 microM and 18.06 +/- 0.08 microM, respectively, whereas for O(2-), the IC(50) of nicardipine in PMA, fMLP and A23187-stimulated human and rabbit neutrophils was 55.41 +/- 0.09 microM and 58.43 +/- 0.03 microM, 45.21 +/- 0.13 microM and 37.19 +/- 0.53 microM, 33.54 +/- 0.09 microM and 30.54 +/- 0.29, respectively. The mechanisms underlying the inhibition of elastase and superoxide anion radicals by nicardipine appear related to an inhibiting effect on the mobilisation of cytosolic calcium and on activation of protein kinase C (PKC). These antioxidant and anti-elastasic activities contribute to the properties of nicardipine, as positive side effects of its antihypertensive activity and may be useful to prevent inflammatory disorders (tissue damage, oxidative injury) involved in the pathogenesis of hypertension.