Nifedipine affects neutrophil functions by a non-calcium-mediated mechanism.
Cardiac disorders are known to be associated with neutrophil infiltration. The central role of calcium in modulating neutrophil functions prompted us to examine whether Ca2+ channel blockers could affect vital neutrophil functions in mice. In vitro exposure of mice neutrophil to nifedipine resulted in inhibition of superoxide production in a dose-dependent manner. However, the inhibition of calcium uptake elicited by nifedipine did not appear to account for the observed effect since the extracellular Ca2+ enrichment and depletion did not produce a significant reversal of inhibition. In addition, there was significant inhibition (P less than 0.01) of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity. Cytosolic-free Ca2+, as measured by Quin-2AM fluorescence, showed no significant change indicating that the effect was independent of inhibition of Ca2+ influx. The hypothesis was substantiated by loss of neutrophilic functions following long-term administration of nifedipine. Our data indicate that nifedipine impairs neutrophil functions and support the hypothesis that Ca2+ antagonists also affect cellular functions by non Ca2+ mediated processes.
Nalini
K
K
Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Andrabi
K
K
Ganguly
N K
NK
Wahi
P L
PL
D000818:Animals; D002118:Calcium / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D008297:Male; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D009543:Nifedipine; D002118:Calcium