Protective effect of a novel calcium blocker, S-312-d, on ischemic acute renal failure in rat.
The effect of the calcium blocker S-(+)-methyl 4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitro-phenyl)thieno[2,3-b]pyridine- 5-carboxylate (S-312-d) on ischemic acute renal failure (ARF) was studied in rats. Ischemic ARF was induced by temporary (30-60 min) clamping of the left kidney 2 weeks after contralateral right nephrectomy. Plasma creatinine, creatinine clearance, urinary osmolality and fractional excretion of sodium were used to test the effectiveness of the drug. S-312-d (0.01-0.1 mg/kg b.wt. i.v.) administration before ischemia offered dose-dependent protection against the functional impairment induced by ischemia. This effect was accompanied by an increase in the survival rate of ischemic rats. S-312-d given after ischemia was not effective. The renal cortical edema induced by ischemia was significantly reduced by pretreatment with S-312-d. The increase in renal tissue calcium content observed after ischemia was also suppressed by S-312-d. Comparison with other established calcium blockers indicated S-312-d to be a good candidate for protection against ischemic ARF. These findings indicate that S-312-d may be clinically useful against renal ischemia.
Shimizu
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kawabata
T
T
Nakamura
M
M
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C059447:S 312; D002118:Calcium