European Heart Journal (1991) 12 (Supplement D), 105-107

Nifedipine affects neutrophil functions by a non-calcium-mediated mechanism K. NALINI,* K. ANDRABI, N.K.

GANGULY AND P.L.

WAHI*

Departments of Cardiology* and Experimental Medicine, Postgraduate Institue of Medical Education and Research, Chandigarh 160012, India KEY WORDS: Neutrophil, calcium, nifedipine, superoxide.

Introduction It is increasingly implied that the interaction of calcium antagonistic drugs with non-cardiac cells, for example, blood cells, intestinal cells, nerve cells, etc has tended to generalize their specificity1'"'1. Similarly, the therapeutic administration of this class of drugs in cardiac dysfunction could be associated with many as yet unnoticed effects. The in vitro effects of calcium channel blockers on neutrophil functions have been reported'4', but with limited implications about their therapeutic use. The present study was undertaken to investigate the influence of nifedipine (calcium channel blocker) on neutrophil functions. Nifedipine was chosen because of its widespread use and greater potency compared to other calcium channel blockers in cardiovascular therapy.

photometrically at 340 nm, as already described'71; calcium uptake was measured by the rapid sampling silicone oil method'81, cytosolic free calcium by spectrofluorimetry[9] and other neutrophilic functions by standard procedures described elsewhere'10"131. Results and discussion

Figure 1 shows that superoxide production by neutrophils stimulated with PMA (phorbol myristic acetate) was inhibited by nifedipine over a wide range of concentrations. This observation was rather unexpected E IT)

Materials and methods

Male albino white mice (30-35 g) were used for the study. Nifedipine (Boehringer-Knoll, India) was dissolved in a minimum quantity of ethanol with the volume made up in normal saline. For in vivo studies animals received the drug orally corresponding to a plasma concentration of 70-90 ngml" 1 . 45Ca was purchased from BARC, India; phorbol myristic acetate (PMA), NADPH, Quin-2AM, and ferricytochrome C were obtained from Sigma, USA. Polymorphonuclear leucocyte (PMN) isolation was carried out by density gradient centrifugation of the venous blood as described previously'51; assessment of OJ radical generation was carried out by measuring the conversion of ferricytochrome to ferro-cytochrome[61. NADPH oxidase activity was measured spectro-

100

500

OOO

Nifedipine (ng.ml'1)

Figure 1 Nifedipine-induced inhibition of superoxide production. Influence of extracellular Ca 2+ enrichment and dictation: neutrophils (1 x 10*) were stimulated with PMA (lOOngmr 1 ) in the presence of different concentrations of nifedipine. The stimulation was carried out in the absence (O—O) or in the presence ( • — • ) of Ca 2+ (10 HIM) or in presence of EGTA (4 mM) (A—A). Superoxide production was measured by a standard cytochrome 2+ Corrtipondence: Dr P.L Wahi, Department of Cardiology, Postgraduate C reduction procedure. The values for Ca and2+EGTA are not significantly different from the values without Ca . Institute of Medical Education and Research, Chandigarh 160012, India. 0195-668X/91/OD0104 + 03 $03.00/0

© 1991 The European Society of Cardiology

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 5, 2016

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

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 ...
184KB Sizes 0 Downloads 0 Views