Verapamil reverses abnormal [Ca2+]i and carbohydrate metabolism of PMNL of dialysis patients.
The basal levels of cytosolic calcium ([Ca2+]i) of polymorphonuclear leukocytes (PMNL) are elevated in hemodialysis (HD) patients, and this abnormality has been implicated in the dysfunction of the PMNL of these patients. The elevated [Ca2+]i appears to be due to PTH-induced entry of calcium into PMNL, an action that may be prevented by calcium channel blockers. We examined [Ca2+]i and carbohydrate metabolism of PMNL of normal subjects and of HD patients before, after eight to nine weeks of verapamil therapy (120 mg/day), and after eight to ten weeks of discontinuation of verapamil treatment. In HD patients, the basal levels of [Ca2+]i of PMNL are elevated and their glucose uptake, the activity of total and active forms of glycogen synthetase, and glycogen content are reduced compared to values in normal subjects (P < 0.01). These derangements were normalized after verapamil therapy and re-emerged after discontinuation of treatment with verapamil despite no change in blood levels of PTH. The results indicate that the elevation in [Ca2+]i of PMNL and the consequent derangements in carbohydrate metabolism of these cells are treatable with a calcium channel blocker. The data assign a valuable role for calcium channel blockers for the amelioration of some aspects of cell dysfunction of uremia.
Hörl
W H
WH
Department of Medicine, University of Vienna, Austria.
Haag-Weber
M
M
Mai
B
B
Massry
S G
SG
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006003:Glycogen / Q000097:blood; D006006:Glycogen Synthase / Q000097:blood; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009994:Osmolar Concentration; D006435:Renal Dialysis; D014700:Verapamil / Q000627:therapeutic use*
D001786:Blood Glucose; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006003:Glycogen; D014700:Verapamil; D006006:Glycogen Synthase; D002118:Calcium