Prevention of acute cyclosporin nephrotoxicity by verapamil and atrial natriuretic factor in the rat.
Nephrotoxicity is the most common and important side-effect of cyclosporin (CsA) therapy. CsA alters renal haemodynamics with a reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistances (RVR). The present experimental study investigates whether verapamil or atrial natriuretic factor (ANF) are able to prevent the nephrotoxicity of CsA. All studies were conducted in an in-situ autoperfused rat kidney model which allows continuous measurement of renal blood flow without dissection of the renal artery. CsA as a 40 mg/kg bolus dose significantly decreased RBF (from 2.15 +/- 0.1 and 2.19 +/- 0.1 before CsA, to 1.29 +/- 0.16 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05), and GFR (from 0.14 +/- 0.1 and 0.13 +/- 0.01 before CsA, to 0.08 +/- 0.01 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05). CsA significantly increased RVR (from 9.5 +/- 0.73 and 9.8 +/- 0.78 before CsA, to 16.7 +/- 2.9 mmHg x min/ml 60 min after CsA administration) (P < 0.05). Verapamil pretreatment (as continuous intrarenal infusion at the rate of 1.25 micrograms/kg/min) attenuated the fall in GFR (from 0.16 +/- 0.01 and 0.19 +/- 0.03 ml/min/100 g before CsA to 0.20 +/- 0.05 ml/min/100 g BW, 60 min after CsA administration) (NS) and in RBF (from 2.42 +/- 0.2 and 2.6 +/- 0.22 ml/min/100 g before CsA to 1.79 +/- 0.17 ml/min/100 g BW, 60 min after CsA administration (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Bagnis
C
C
Department of Nephrology, Hôpital Pitie-Salpetriere, Paris, France.
Deray
G
G
Dubois
M
M
Jacquiaud
C
C
Bitker
M O
MO
Jacobs
C
C
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
C472610:atrial natriuretic peptide, rat; D016572:Cyclosporine; D009320:Atrial Natriuretic Factor; D014700:Verapamil