Résumé
Chronic treatment with dihydropyridines and to a lesser extent other calcium antagonists often cause peripheral edema without fluid retention. To test the possibility that calcium antagonists affect extracellular fluid partition between plasma and interstitium, we compared the effects of a benzothiazepine derivate diltiazem, a dihydropyridine derivate nicardipine and vehicle in binephrectomized anesthetized rats by measuring changes in hematocrit and plasma protein concentration. Forty minutes infusion of low dose of nicardipine and diltiazem (0.1 and 10 micrograms/kg/min respectively) had no significant effect on blood pressure (-2 +/- 2 and -4 +/- 3% respectively); nicardipine increased hematocrit by 5.6 +/- 0.5% (p less than 0.05); while diltiazem had no significant effect as compared to the vehicle (+1.5 +/- 0.3 and +1.5 +/- 0.3% respectively). The calculated loss of plasma volume during nicardipine infusion was 9.2 +/- 0.8% as compared to 2.5 +/- 0.6% and 2.7 +/- 0.6% in rats receiving diltiazem and vehicle respectively. Infusion of higher doses of nicardipine and diltiazem (1 and 100 micrograms/kg/min respectively) decreased blood pressure by 21 +/- 2 and 19 +/- 2% while the changes in hematocrit were not different than those observed with with the lower doses (5.5 +/- 0.6 and 1.4 +/- 0.3% respectively). To document and localize an alteration in vascular leak of proteins induced by the drugs, albumin-bound Evans Blue (EB) extravasation was measured spectrophotometrically in different tissues after extraction by formamide. Nicardipine but not diltiazem increased vascular permeation of EB-albumin in skeletal and cardiac muscle. No change was observed in brain, liver, spleen as compared to rats receiving the vehicle.Chronic treatment with dihydropyridines and to a lesser extent other calcium antagonists often cause peripheral edema without fluid retention. To test the possibility that calcium antagonists affect extracellular fluid partition between plasma and interstitium, we compared the effects of a benzothiazepine derivate diltiazem, a dihydropyridine derivate nicardipine and vehicle in binephrectomized anesthetized rats by measuring changes in hematocrit and plasma protein concentration. Forty minutes infusion of low dose of nicardipine and diltiazem (0.1 and 10 micrograms/kg/min respectively) had no significant effect on blood pressure (-2 +/- 2 and -4 +/- 3% respectively); nicardipine increased hematocrit by 5.6 +/- 0.5% (p less than 0.05); while diltiazem had no significant effect as compared to the vehicle (+1.5 +/- 0.3 and +1.5 +/- 0.3% respectively). The calculated loss of plasma volume during nicardipine infusion was 9.2 +/- 0.8% as compared to 2.5 +/- 0.6% and 2.7 +/- 0.6% in rats receiving diltiazem and vehicle respectively. Infusion of higher doses of nicardipine and diltiazem (1 and 100 micrograms/kg/min respectively) decreased blood pressure by 21 +/- 2 and 19 +/- 2% while the changes in hematocrit were not different than those observed with with the lower doses (5.5 +/- 0.6 and 1.4 +/- 0.3% respectively). To document and localize an alteration in vascular leak of proteins induced by the drugs, albumin-bound Evans Blue (EB) extravasation was measured spectrophotometrically in different tissues after extraction by formamide. Nicardipine but not diltiazem increased vascular permeation of EB-albumin in skeletal and cardiac muscle. No change was observed in brain, liver, spleen as compared to rats receiving the vehicle.