Effects of cyclosporin on renal microcirculation.
To evaluate renal microcirculation during acute cyclosporin (CsA) administration (50 mg/kg, i.v.), seven euvolaemic Munich-Wistar rats were studied. CsA infusion caused a significant decrease in total glomerular filtration rate (GFR) (0.96 +/- 0.04 vs 0.47 +/- 0.07 ml/min) and in single-nephron GFR (SNGFR) (27.90 +/- 3.4 vs 14.02 +/- 3.5 nl/min). The efferent arteriolar resistance increased substantially (P less than 0.05) while the afferent resistance rose moderately. Consequently, there was an increase (P less than 0.05) in mean glomerular capillary hydraulic pressure (PGC), from 45 +/- 1 to 55 +/- 4 mmHg, together with an important decrease in mean glomerular plasma flow rate (QA), from 100 +/- 17 to 44 +/- 13 nl/min. Since tubular hydraulic pressure was maintained unaltered, an elevated transglomerular hydraulic pressure difference was observed (P less than 0.05). The lower values of SNGFR were accounted for by both the decrease in QA and in the glomerular ultrafiltration coefficient (Kf). The latter was reduced from 0.096 +/- 0.03 to 0.031 +/- 0.010 nl/sec per mmHg (P less than 0.05) by CsA. Additionally, three groups of Munich-Wistar rats were previously treated with captopril (2 mg/kg per h, i.v.), verapamil (20 micrograms/kg per min, i.v.) or indomethacin (2 mg/kg, i.v.). Both captopril and verapamil minimised the renal effects of CsA, with a decline of approximately 25% instead of approximately 50% on GFR and RPF. Thus CsA infusion caused a decline on SNGFR due to an important reduction in QA and Kf with an impressive increase on arteriolar resistance, a mark of angiotensin II stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D003524:Cyclosporins; D002216:Captopril; D014700:Verapamil; D007213:Indomethacin