The influence of the cyclosporine vehicle, cremophor EL, on renal microvascular blood flow in the rat.
Cyclosporine nephrotoxicity may be due to glomerular hypoperfusion. Previous experimental and clinical studies have demonstrated a decrease in renal blood flow and an increase in renal vascular resistance. Cremophor EL, which is the vehicle in which CsA is dissolved, is thought to be a factor involved in intrarenal arteriolar vasoconstriction. To determine the relative contributions of the vehicle and CsA to intrarenal arteriolar vasoconstriction, we used in vivo videomicroscopy and Doppler velocimetry to measure changes in renal microvascular blood flow in the rat. A 5-min intravenous infusion of 20 mg/kg of CsA resulted in a 17% mean reduction (P less than 0.05) in the diameter of preglomerular interlobular arterioles and an associated 60% reduction (P less than 0.05) in microvascular blood flow by 15 min. Cremophor EL/ethanol equivalent caused less vasoconstriction (up to 10%) but resulted in a 42% mean decrease (P less than 0.05) in microvascular blood flow, probably secondary to a 38% mean decrease (P less than 0.05) in cardiac output and 13% decrease in arterial pressure. We conclude that cremophor EL does contribute to in vivo reduction of preglomerular microvascular blood flow in the rat. This may be particularly important when using this intravenous preparation in the study of CsA nephrotoxicity.
Abraham
J S
JS
Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
Bentley
F R
FR
Garrison
R N
RN
Cryer
H M
HM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D014465:Ultrasonics; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D003524:Cyclosporins; D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D005990:Glycerol