BACKGROUND: Sodium nitroprusside (SNP) and molsidomine are used in the treatment of coronary heart disease. Since the neutrophils play a pathological role in ischaemic heart disease, it is important to understand the direct action of nitrovasodilators on their function. AIM: We examined the effects of SNP and 3-morpholinosydnonimine (SIN-1, molsidomine metabolite) on the respiratory burst of human neutrophils and their adhesion in vitro . The influence of nitric oxide (NO)donors on the activity of protein kinases, which are involved in the NADPH oxidase activation, was also investigated. METHODS: The respiratory burst of neutrophils was determined by chemiluminescence and fluorescence methods, while the adhesion was assayed by adherence of neutrophils to the plastic surface. RESULTS: NO donors decreased the oxidative burst of activated neutrophils. However, the effects of SNP and SIN-1 strongly depended on the treatment time of neutrophils and on the stimulus employed to cells activation. Protein kinase C inhibitor did not prevent the inhibitory effect of SIN-1, but diminished the inhibitory effect of SNP on the neutrophils' respiratory burst. Protein tyrosine kinase inhibitor did not affect the action of SNP, but diminished the inhibitory effect of SIN-1 on fMLP-stimulated but not on PMA stimulated oxidative burst of neutrophils. This suggests that SNP action is mainly associated with protein kinase C, while SIN-1 is associated with protein tyrosine kinase activity. We also found that SIN-1 but not SNP diminished the adhesive activity of neutrophils. CONCLUSIONS: Our data show that SIN-1 biological effect on some neutrophils activity is different from both spermine NONOate and SNP, and mainly depends on ONOO(-), while SNP action is mediated by NO.
BACKGROUND:Sodium nitroprusside (SNP) and molsidomine are used in the treatment of coronary heart disease. Since the neutrophils play a pathological role in ischaemic heart disease, it is important to understand the direct action of nitrovasodilators on their function. AIM: We examined the effects of SNP and 3-morpholinosydnonimine (SIN-1, molsidomine metabolite) on the respiratory burst of human neutrophils and their adhesion in vitro . The influence of nitric oxide (NO)donors on the activity of protein kinases, which are involved in the NADPH oxidase activation, was also investigated. METHODS: The respiratory burst of neutrophils was determined by chemiluminescence and fluorescence methods, while the adhesion was assayed by adherence of neutrophils to the plastic surface. RESULTS: NO donors decreased the oxidative burst of activated neutrophils. However, the effects of SNP and SIN-1 strongly depended on the treatment time of neutrophils and on the stimulus employed to cells activation. Protein kinase C inhibitor did not prevent the inhibitory effect of SIN-1, but diminished the inhibitory effect of SNP on the neutrophils' respiratory burst. Protein tyrosine kinase inhibitor did not affect the action of SNP, but diminished the inhibitory effect of SIN-1 on fMLP-stimulated but not on PMA stimulated oxidative burst of neutrophils. This suggests that SNP action is mainly associated with protein kinase C, while SIN-1 is associated with protein tyrosine kinase activity. We also found that SIN-1 but not SNP diminished the adhesive activity of neutrophils. CONCLUSIONS: Our data show that SIN-1 biological effect on some neutrophils activity is different from both spermine NONOate and SNP, and mainly depends on ONOO(-), while SNP action is mediated by NO.