Effect of cyclosporine on endothelial albumin leakage in rats.
Short-term treatment of rats with cyclosporine (cyclosporine A [CsA]; Sandimmune) results in a marked reduction in intravascular plasma volume, a factor that might contribute to the renal dysfunction associated with this potent immunosuppressant. To examine the role of plasma extravasation in CsA-induced hypovolemia, intravascular plasma volumes (PV), blood volumes, [125I]albumin disappearance, and changes in hematocrit (Hct) were measured in Inactin-anesthetized rats subjected to minimal surgery. The rats were treated for 3 wk with either 25 mg/kg/day of CsA s.c. or vehicle. Plasma creatinine and urea were significantly elevated, and magnesium was reduced in the CsA group (N = 6) as compared with controls (CON) (N = 6). CsA treatment had no effect on urinary protein and albumin excretion. Blood volume was significantly lower in CsA than in CON (8.4 +/- 0.5 versus 10.6 +/- 0.3 mL/100 g body wt) as was PV (4.3 +/- 0.2 versus 5.5 +/- 0.2 mL/100 g body wt). Two hours after injection, plasma [125I]albumin concentration had fallen by 41 +/- 4% in CsA versus 23 +/- 5% in CON. Because Hct, and, hence PV, was unchanged in both groups during these 2 h, these data indicate enhanced endothelial albumin leakage in the CsA group. In two additional groups of six rats each, acute volume expansion with fresh whole blood (2 mL/100 g body wt) resulted in extravasation of plasma. Hct rose by 8.0 +/- 0.2% in CsA versus 3.8 +/- 0.2% in CON after 150 min, corresponding to 27 +/- 3 and 15 +/- 2% decreases in total PV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Moore
L C
LC
Department of Physiology and Biophysics, SUNY, Stony Brook 11794.
Mason
J
J
Feld
L
L
Van Liew
J B
JB
Kaskel
F J
FJ
D000818:Animals; D001803:Blood Transfusion; D001810:Blood Volume / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006400:Hematocrit; D008297:Male; D010949:Plasma / Q000737:chemistry; D010952:Plasma Substitutes / Q000494:pharmacology; D010953:Plasma Volume / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*
D010952:Plasma Substitutes; D012709:Serum Albumin; D016572:Cyclosporine