Effect of different calcium antagonists on transcapillary fluid shift.
Chronic treatment with dihydropyridines, and to a lesser extent other calcium antagonists, often results in peripheral edema without fluid retention. The possibility that calcium antagonists affect extracellular fluid volume partition was tested by comparing the effects of nicardipine (Nic), diltiazem (Dil) and Vehicle (Veh) on hematocrit and plasma protein concentration in anephric anesthetized rats. In response to a 45 min infusion of Nic (0.1 or 1 micrograms/kg/min) and Dil (10 or 100 micrograms/kg/min), blood pressure decreased by 4 or 21%, and 4 or 19%, respectively, whereas hematocrit increased only with both doses of Nic (5.3 +/- 0.2 and 5.5 +/- 0.2%). Plasma protein concentration also increased significantly, although slightly, in the Nic group. The possibility of protein extravasation was then assessed using Evans blue dye as a marker. The drug-induced extravasation of dyed albumin in skeletal and cardiac muscles, but not other organs, was significantly increased following Nic, as compared to Dil or Veh. These observations suggest that two structurally different calcium antagonists used at equihypotensive doses may exert different effects on extracellular fluid partition.
Valentin
J P
JP
Department of Medicine, Centre Hospitalier Universitaire, Montpellier, France.
Ribstein
J
J
Halimi
J M
JM
Mimran
A
A
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D005070:Evans Blue; D006400:Hematocrit; D008297:Male; D009392:Nephrectomy; D009529:Nicardipine / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism
D001798:Blood Proteins; D002121:Calcium Channel Blockers; D012709:Serum Albumin; D005070:Evans Blue; D009529:Nicardipine; D004110:Diltiazem