Amlodipine prevents and reverses the elevation in [Ca2+]i and the impaired phagocytosis of PMNL of diabetic rats

Abstract

BACKGROUND: High glucose concentration, through the activation of calcium channels, augments in vitro calcium entry into cells and leads to elevation in the basal levels of [Ca2+]i, the latter causes cell dysfunction. DESIGN OF STUDY: The present study examined whether streptozotocin-induced diabetes mellitus in rats causes a rise in [Ca2+]i of PMNL and impairs their phagocytosis and whether treatment of these rats with the calcium channel blocker, amlodipine, prevents and/or reverses these derangements. Amlodipine was given either from day one of diabetes or after 3 or 12 days of established diabetes. RESULTS: The [Ca2+]i of PMNL was elevated and their phagocytosis was reduced after one day of diabetes. These derangements were present and became more marked with longer duration of diabetes. There was a direct and significant correlation (r = 0.88) between [Ca2+]i of PMNL and blood glucose and an inverse relationship between phagocytosis and blood glucose (r = 0.83) or [Ca2+]i (r = 0.67). Three days of amlodipine therapy were required to completely prevent or reverse the elevation in [Ca2+]i of PMNL. This action of the drug occurred despite the hyperglycaemia. Amlodipine produced marked and significant improvements in phagocytosis but the values remained modestly below normal. Amlodipine given to normal rats did not affect [Ca2+]i or phagocytosis of PMNL. CONCLUSION: The results show that (i) [Ca2+]i of PMNL increases and phagocytosis decreases rapidly after the induction of diabetes; (ii) treatment of diabetic rats with amlodipine normalizes [Ca2+]i of PMNL and markedly improves their phagocytosis, despite hyperglycemia; (iii) high [Ca2+]i is responsible, in major part, for the impaired phagocytosis but other factors are also operative; and (iv) calcium channel blockers could prove useful in the treatment of the metabolic and functional derangements of PMNL in patients with poorly controlled diabetes.