[Effects of verapamil on cyclosporine. A (CsA)-induced nephropathy in ischemic kidney model in rats: changes in systemic hemodynamics and hepatic and renal microsomal cytochrome P-450].
We have examined the effect of verapamil on CsA-induced nephropathy by measurement of systemic hemodynamics including each organ blood flow using the microsphere method in ischemic kidney model of hemi-nephrectomized Wistar rats. Hepatic and renal microsomal cytochrome P-450 contents and their enzyme activities were measured to study the correlation between CsA-induced nephropathy and induction of hepatic and renal microsomal cytochrome P-450. All rats were hemi-nephrectomized (l-nephrectomy) and were classified into the following 6 groups: 1) control groups, 2) CsA at a dose of 40 mg/kg per day orally for 7 days (CsA group), 3) Oral administration of verapamil for 7 days in the CsA group (CsA + V group), 4) 20 min clamping of the remaining right kidney pedicle (Ischemic, Is group), 5) CsA was administered in the Is group (Is + CsA group), 6) Addition of verapamil to CsA in the Is + CsA group (Is + CsA + V group). Verapamil was given in the drinking water and the average dose calculated from the amount of drinking was 4.7 +/- 1.0 mg/kg per day and 5.2 +/- 0.7 mg/kg per day for the CsA + V group and the Is + CsA + V group, respectively. CsA caused significant increases in BUN and serum creatinine (sCr) with a significant decreases in renal inulin clearance (CIn) in all groups. When compared with the Is group, CsA caused significant decreases in cardiac output and all organ blood flow especially in renal blood flow with significant increases in BUN and sCr in the Is + CsA group.2+ degree of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Kishimoto
T
T
Department of Urology, Osaka City University Medical School.
Tsujino
T
T
Nakatani
T
T
Kim
T
T
Ohyama
A
A
Yoshimura
R
R
Sakamoto
W
W
Maekawa
T
T
Kawashima
H
H
Kusunose
E
E
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007511:Ischemia / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000517:prevention & control; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D014700:Verapamil