Effect of cyclosporine a on glucose interstitial concentration in renal cortex and medulla from rats.
OBJECTIVE
To standardize microdialysis in rat kidneys and address cyclosporine A (CsA) effects on renal cortex and medulla interstitial glucose.


METHODS
Munich-Wistar rats were treated with vehicle or CsA (15 mg/kg/day) for 3 weeks. Glucose was assessed by spectrophotometry in dialysate samples from cortex, medulla and arterial plasma. Plasma insulin was measured by radioimmunoassay. Renal blood flow (RBF) was measured by Doppler ultrasound. Creatinine and urea were measured by spectrophotometry.


RESULTS
CsA significantly increased the plasma levels of urea and creatinine (1.5 +/- 0.20 vs. 0.73 +/- 0.03 mg/dl in controls, p < 0.05). Medullary glucose in control was 44% lower than arterial glucose (56 +/- 6 vs. 101 +/- 8 mg/dl, p < 0.05). At the same time, CsA increased arterial (163 +/- 35 vs. 101 +/- 8 mg/dl in controls, p < 0.05) and medullary interstitial glucose (100 +/- 18 vs. 56 +/- 6 mg/dl in controls, p < 0.05), but did not affect cortical glucose (114 +/- 21 vs. 90 +/- 11 mg/dl in controls). These changes occurred in the presence of a decreased plasma insulin level (2.7 +/- 0.2 vs. 9.3 +/- 0.4 microU/ml in controls, p < 0.05). The increment in medullary glucose in CsA group occurred despite a reduction in RBF (4.6 +/- 0.8 vs. 6.5 +/- 1.0 ml/min/kidney in controls, p < 0.05).


CONCLUSIONS
Microdialysis was an adequate tool to investigate in vivo regulation of renal glucose metabolism. Renal glucose uptake was dependent on medullary cells and CsA treatment induced diabetogenic effects on renal medulla in situ.
Navegantes
Luiz Carlos Carvalho
LC
Laboratory of Endocrinology and Metabolism, Department of Molecular Biology, São José do Rio Preto Medical School, São Paulo, Brazil.
Mendes
Glória Elisa Florido
GE
Lira
Eduardo Carvalho
EC
Kettelhut
Isis do Carmo
Ido C
Baptista
Maria Alice Sperto Ferreira
MA
Burdmann
Emmanuel A
EA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002404:Catheterization; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects*; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D017551:Microdialysis / Q000379:methods / Q000592:standards; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D016572:Cyclosporine