Calcium entry-blockade with verapamil in cyclosporine A plus ischemia induced acute renal failure in rats.
The possible alleviating effect of verapamil, a calcium entry blocker, on the resulting renal damage from the combination of a short episode of ischemia and CyA was studied in rats. Immediately after right nephrectomy the rats were divided into five experimental groups. Group 1: left renal pedicle clamping for 20 minutes. Group 2: as group 1 plus CyA 60 mg/kg bw i.p. Group 3: CyA as in group 2 but sham operated. Group 4: as group 2 plus verapamil 10 mg% in the drinking water. Group 5: as group 3 plus verapamil given as in group 4. The experiments lasted 4 days. By analysis of variance: CyA + ischemia (group 2) showed lower creatinine clearance (p less than 0.001), higher blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.05) and fractional excretion of potassium (p less than 0.01) and fractional excretion of negative free water clearance (p less than 0.001) compared to ischemia alone (group 1). The CyA + ischemia rats treated with verapamil had higher creatinine clearance (p less than 0.05), lower blood urea (p less than 0.01), fractional excretion of sodium (p less than 0.001), fractional excretion of potassium (p less than 0.001) and fractional excretion of negative free water clearance (p less than 0.05) compared with the untreated verapamil CyA + ischemia group. The CyA + sham operated verapamil treated group had similar creatinine clearance with the corresponding verapamil untreated group. The CyA + ischemia group had the higher mean daily body weight reduction compared with all other groups. Histology showed more vacuolization of tubular epithelial cells in the CyA + ischemia than in ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Iaina
A
A
Herzog
D
D
Cohen
D
D
Gavendo
S
S
Kapuler
S
S
Serban
I
I
Schiby
G
G
Eliahou
H E
HE
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003524:Cyclosporins / Q000633:toxicity*; D005260:Female; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply*; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D014700:Verapamil / Q000627:therapeutic use*
D003524:Cyclosporins; D014700:Verapamil