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Time Course of the Effect of Nifedipine Therapy and Its Discontinuation on [Ca2+]i and Phagocytosis of Polymorphonuclear Leukocytes from Hemodialysis Patients

Time Course of the Effect of Nifedipine Therapy and Its Discontinuation on [Ca2+]i and... The abnormalities in [Ca<sup>2+</sup>]<sub>i</sub> and phagocytosis of polymorphonuclear leukocytes (PMNLs) from hemodialysis (HD) patients are significantly improved by their treatment with nifedipine. However, the rapidity with which this agent induces its benefical effect and whether these derangements re-emerge after cessation of therapy are not known. We studied 5 HD patients before, during and after treatment with nifedipine. Before treatment with this agent, the basal levels of [Ca<sup>2+</sup>]<sub>i</sub> of PMNLs were markedly elevated 73 ± 3.6 nM (normal: 42 ± 0.09 nM) and their phagocytic ability markedly reduced (73 ± 7.4 µgoil/l0<sup>7</sup>PMNLs/min (normal: 153 ± 3.8 µg oil/l0<sup>7</sup>PMNLs/min). After 1 month of therapy, [Ca<sup>2+</sup>]<sub>i</sub> fell significantly (p < 0.01) to 53 ± 1.0 nM with further decrement of a value of 40 ± 0.9 nM by the end of 3 months of treatment. The levels of [Ca<sup>2+</sup>]<sub>i</sub> rose significantly (p < 0.01) to 61 ± 2.1 nM after 1 month of cessation of therapy and were 69 ± 2.5 nM by the end of 5 months; these values are not different from those observed before therapy. Phagocytosis improved significantly (p < 0.01) after 1 month of nifedipine therapy (107 ± 3.9 µg oil/l0<sup>7</sup> PMNLs/min) with no further improvement during the other 2 months of therapy. Only modest decrement in phagocytosis occurred during the first 3 months after cessation of nifedipine administration; marked and significant impairment (p < 0.01) in phagocytosis (80 ± 2.6 µg oil/l0<sup>7</sup> PMNLs/min) became evident at the end of the fifth month. The results show that (1) nifedipine treatment of HD patients rapidly reversed the elevation in [Ca<sup>2+</sup>]<sub>i</sub> of their PMNLs but discontinuation of the therapy is followed by rapid re-emergence of the elevation in the [Ca<sup>2+</sup>]<sub>i</sub> of the PMNLs; (2) nifedipine therapy causes rapid and significant, but only partial, improvement of phagocytosis, by PMNL of HD patients; almost 5 months is needed before a significant deterioration in phagocytosis becomes evident after stopping nifedipine treatment; (3) the elevation in [Ca<sup>2+</sup>]<sub>i</sub> of PMNLs of HD patients plays an important role in the pathogenesis of impaired phagocytosis but is only partially responsible for their derangement, and (4) the beneficial effect of nifedipine therapy on phagocytosis makes this drug a useful therapeutic tool to aid HD patients in their fight against infection. Polymorphonuclear leukocytes (PMNL) from uremic patients have elevated basal levels of cytosolic calcium ([Ca2+]) [1], reduced ATP content [1], and impaired phagocytosis [1-3]. We have previously shown that PMNLs from dialysis patients treated with nifedipine have almost normal [Ca2+]<sub>i</sub>, ATP content and phagocytosis [4]. These observations indicate that this calcium channel blocker can reverse the derangements in the metabolism and function of the PMNL of dialysis patients. However, the rapidity with which the treatment with nifedipine induces this beneficial effect, and whether the derangements in [Ca2+]<sub>i</sub> and phagocytosis of PMNL re-emerge after discontinuation of nifedipine therapy are not known. The present study examined these issues to further characterize the effect of nifedipine on PMNL function in dialysis patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Nephrology Karger

Time Course of the Effect of Nifedipine Therapy and Its Discontinuation on [Ca2+]i and Phagocytosis of Polymorphonuclear Leukocytes from Hemodialysis Patients

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Publisher
Karger
Copyright
© 1997 S. Karger AG, Basel
ISSN
0250-8095
eISSN
1421-9670
DOI
10.1159/000169065
Publisher site
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Abstract

The abnormalities in [Ca<sup>2+</sup>]<sub>i</sub> and phagocytosis of polymorphonuclear leukocytes (PMNLs) from hemodialysis (HD) patients are significantly improved by their treatment with nifedipine. However, the rapidity with which this agent induces its benefical effect and whether these derangements re-emerge after cessation of therapy are not known. We studied 5 HD patients before, during and after treatment with nifedipine. Before treatment with this agent, the basal levels of [Ca<sup>2+</sup>]<sub>i</sub> of PMNLs were markedly elevated 73 ± 3.6 nM (normal: 42 ± 0.09 nM) and their phagocytic ability markedly reduced (73 ± 7.4 µgoil/l0<sup>7</sup>PMNLs/min (normal: 153 ± 3.8 µg oil/l0<sup>7</sup>PMNLs/min). After 1 month of therapy, [Ca<sup>2+</sup>]<sub>i</sub> fell significantly (p < 0.01) to 53 ± 1.0 nM with further decrement of a value of 40 ± 0.9 nM by the end of 3 months of treatment. The levels of [Ca<sup>2+</sup>]<sub>i</sub> rose significantly (p < 0.01) to 61 ± 2.1 nM after 1 month of cessation of therapy and were 69 ± 2.5 nM by the end of 5 months; these values are not different from those observed before therapy. Phagocytosis improved significantly (p < 0.01) after 1 month of nifedipine therapy (107 ± 3.9 µg oil/l0<sup>7</sup> PMNLs/min) with no further improvement during the other 2 months of therapy. Only modest decrement in phagocytosis occurred during the first 3 months after cessation of nifedipine administration; marked and significant impairment (p < 0.01) in phagocytosis (80 ± 2.6 µg oil/l0<sup>7</sup> PMNLs/min) became evident at the end of the fifth month. The results show that (1) nifedipine treatment of HD patients rapidly reversed the elevation in [Ca<sup>2+</sup>]<sub>i</sub> of their PMNLs but discontinuation of the therapy is followed by rapid re-emergence of the elevation in the [Ca<sup>2+</sup>]<sub>i</sub> of the PMNLs; (2) nifedipine therapy causes rapid and significant, but only partial, improvement of phagocytosis, by PMNL of HD patients; almost 5 months is needed before a significant deterioration in phagocytosis becomes evident after stopping nifedipine treatment; (3) the elevation in [Ca<sup>2+</sup>]<sub>i</sub> of PMNLs of HD patients plays an important role in the pathogenesis of impaired phagocytosis but is only partially responsible for their derangement, and (4) the beneficial effect of nifedipine therapy on phagocytosis makes this drug a useful therapeutic tool to aid HD patients in their fight against infection. Polymorphonuclear leukocytes (PMNL) from uremic patients have elevated basal levels of cytosolic calcium ([Ca2+]) [1], reduced ATP content [1], and impaired phagocytosis [1-3]. We have previously shown that PMNLs from dialysis patients treated with nifedipine have almost normal [Ca2+]<sub>i</sub>, ATP content and phagocytosis [4]. These observations indicate that this calcium channel blocker can reverse the derangements in the metabolism and function of the PMNL of dialysis patients. However, the rapidity with which the treatment with nifedipine induces this beneficial effect, and whether the derangements in [Ca2+]<sub>i</sub> and phagocytosis of PMNL re-emerge after discontinuation of nifedipine therapy are not known. The present study examined these issues to further characterize the effect of nifedipine on PMNL function in dialysis patients.

Journal

American Journal of Nephrology – Karger

Published: Jan 1, 1997

Keywords: Uremia; Calcium channel blockers; Parathyroid hormone

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