In vivo fluorescence microscopy of kidney subcapsular blood flow in mice. Effects of cyclosporine, (NVA2)-cyclosporine, and isradipine, a new calcium antagonist.
The subcapsular kidney microcirculation in mice was observed through a fluorescence microscope, recorded on videotape, and examined for response to infusions of cyclosporine A (CsA) and cyclosporine G (CsG). Coded video recordings were evaluated by a semiquantitative method. CsA infusion (1.6 +/- 0.4 mg/kg/min) induced a nearly complete inhibition of the subcapsular blood flow. At lower infusion rates (0.46 +/- 0.2 mg/kg/min), the blood flow inhibition was less pronounced. CsG infusions at corresponding rates induced significantly less inhibition. Pretreatment with a new calcium antagonist, isradipine (18-20 micrograms/kg bwt), completely prevented the CsA-induced impairment of subcapsular microcirculation. The calcium antagonist, however, did not improve blood flow when administered after induction of inhibition by CsA (16.8 +/- 2.5 mg/kg), emphasizing the importance of pretreatment. This study suggests hypoperfusion due to vasoconstriction as an important pathophysiologic mechanism for CsA-induced nephrotoxicity. CsG, when given at corresponding rates, induced less inhibition of the blood flow. Pretreatment with a calcium antagonist, isradipine, completely prevented a CsA-induced inhibition of blood flow, suggesting a potential value in the prevention of CsA-induced nephrotoxicity.
Rooth
P
P
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235.
Dawidson
I
I
Clothier
N
N
Diller
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology; D005260:Female; D017275:Isradipine; D007672:Kidney Cortex / Q000098:blood supply; D008297:Male; D051379:Mice; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D011292:Premedication; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects
D002121:Calcium Channel Blockers; D003524:Cyclosporins; D011725:Pyridines; D017275:Isradipine