AMLODIPINE PREVENTS AND REVERSES THE ELEVATION IN [CA2+]I AND THE IMPAIRED PHAGOCYTOSIS OF PMNL OF DIABETIC RATS

Background. High glucose concentration, through the activation of calc ium channels, augments in vitro calcium entry into cells and leads to elevation in the basal levels of [Ca2+](i), the latter causes cell dys function. Design of study. The present study examined whether streptoz otocin-induced diabetes mellitus in rats causes a rise in [Ca2+](i) of PMNL and impairs their phagocytosis and whether treatment of these ra ts with the calcium channel blocker, amlodipine, prevents and/or rever ses these derangements. Amlodipine was given either from day one of di abetes or after 3 or 12 days of established diabetes. Results. The [Ca 2+](i) of PMNL was elevated and their phagocytosis was reduced after o ne day of diabetes. These derangements were present and became more ma rked with longer duration of diabetes. There was a direct and signific ant correlation (r=0.88) between [Ca2+](i) of PMNL and blood glucose a nd an inverse relationship between phagocytosis and blood glucose (r=0 .83) or [Ca2+](i) (r=0.67). Three days of amlodipine therapy were requ ired to completely prevent or reverse the elevation in [Ca2+](i) of PM NL. This action of the drug occurred despite the hyperglycaemia. Amlod ipine 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 de creases rapidly after the induction of diabetes; (ii) treatment of dia betic rats with amlodipine normalizes [Ca2+](i) of PMNL and markedly i mproves their phagocytosis, despite hyperglycemia; (iii) high [Ca2+](i ) is responsible, in major part, for the impaired phagocytosis but oth er factors are also operative; and (iv) calcium channel blockers could prove useful in the treatment of the metabolic and functional derange ments of PMNL in patients with poorly controlled diabetes.