The influence of temocapril, an angiotensin converting enzyme inhibitor, on the cyclosporine-induced nephrotoxicity.
OBJECTIVE
We examined the effect of temocapril (Tem), an angiotensin converting enzyme inhibitor (ACEI), on the cyclosporine-induced nephrotoxicity (CsA-NT) in rats.


METHODS
Male Wistar rats were used. Group 1 (G1) received a medium (i.e. olive oil) only, group 2 (G2) received CsA (30 mg./kg./d) only, group 3 (G3) received both CsA (30 mg./kg./d) and Tem (80 micrograms./kg./d), and group 4 (G4) received Tem (80 micrograms./kg./d) only. Each group consisted of 5 animals. Drugs were given orally for fourteen days. Then, renal cortical blood flow (RCBF) and concentrations of serum creatinine (S-Cr), serum potassium (S-K), whole blood CsA (WB-CsA), serum aldosterone (Ald), and plasma renin activity (PRA) were measured. The creatinine clearance (CCr) was also calculated. Kidneys were processed to the light microscopic examination with Bowie stain, and the size of the renin granules (S-RGs) was estimated by an image analysis system.


RESULTS
G2 showed a decrease of RCBF (p < 0.01), an increase of S-Cr (p < 0.01), a decrease of CCr (p < 0.01), an increase of S-K (p < 0.05), and an increase of S-RGs (p < 0.01). Compared with G2, G3 showed significant improvement in RCBF (p < 0.01) and S-Cr (p < 0.05), but still showed significant impairments in all indices (p < 0.01 or p < 0.05, vs control). G4 showed no remarkable changes comparing with G1, except a significant (p < 0.01, vs. control) increase of S-K. G3 showed additional effect on the increase of S-K (p < 0.01, vs. control and G2). Tem showed no significant influence on the WB-CsA level. The serum Ald and PRA levels were not significantly changed by these drugs.


CONCLUSIONS
These data are compatible with the hypothesis that the vasoconstriction of the afferent arterioles (AAs) is a principal mechanism of CsA-NT. The increase of RGs may be the result of both increased production and inhibited secretion of renin.
Ishikawa
A
A
Department of Urology, Hamamatsu University School of Medicine, Japan.
Fujita
K
K
Suzuki
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013841:Thiazepines / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; D016572:Cyclosporine; C055603:temocapril hydrochloride