FK 506: effects on glomerular hemodynamics and on mesangial cells in culture.
FK 506 is a new immunosuppressive drug that, like cyclosporine A (CsA), presents nephrotoxicity. Glomerular hemodynamic studies showed that acute FK 506 infusion (N = 9, 3 mg/kg body wt, i.v. in bolus) caused a 57% reduction in glomerular filtration rate (GFR) (0.74 +/- 0.03 to 0.32 +/- 0.02 ml/min, P < 0.05) and a 40% reduction in single nephron glomerular filtration rate (SNGFR; 43.0 +/- 5.2 to 26.0 +/- 2.5 nl/min, P < 0.05) due to a 25% reduction in glomerular plasma flow rate (QA) (133.4 +/- 19.8 to 99.8 +/- 12.0 nl/min) and a 22% reduction in glomerular ultrafiltration coefficient (Kf; 0.1009 +/- 0.0203 to 0.0790 +/- 0.0130 nl/sec. mm Hg). After 10 days of FK treatment (N = 8, 0.6 mg/kg body wt, i.p.), we observed a reduction of 23% in GFR (0.97 +/- 0.02 to 0.75 +/- 0.04 ml/min, P < 0.05) and of 23% in SNGFR (37.9 +/- 3.0 to 29.1 +/- 1.9 nl/min, P < 0.05) due to a 42% reduction in Kf (0.1486 +/- 0.0101 to 0.0870 +/- 0.0110 nl/sec.mm Hg, P < 0.05) and a 38% reduction in QA (117.6 +/- 10.2 to 73.5 +/- 6.1 nl/min, P < 0.05). The latter was consequent to the increment of 72% in total arteriolar resistance (RT) (3.1 +/- 0.2 to 5.2 +/- 0.5 +/- 0.5 10(10).dyn.sec.cm-5, P < 0.05). Thus, the pattern of FK 506 effect on glomerular hemodynamics was similar in both acute and chronic treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
Hadad
S J
SJ
Biophysics Department, Escola Paulista de Medicina, São Paulo, Brasil.
Souza
E R
ER
Ferreira
A T
AT
Oshiro
M E
ME
Boim
M A
MA
Razvickas
C V
CV
Moura
L A
LA
Schor
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017595:Renal Plasma Flow; D016559:Tacrolimus / Q000494:pharmacology*
D002118:Calcium; D016559:Tacrolimus