Beneficial effects of calcium channel blockers and calmodulin binding drugs on in vitro renal cell anoxia

U. Schwertschlag, R. W. Schrier, P. Wilson

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Proximal tubules (PSTs) of the S1, S2 and S3 segments and cortical collecting tubules (CCTs) were microdissected individually from rabbit kidneys and cultured for 7 days in hormonally defined media. Anoxia was induced by incubation of cultures in normal medium for 45 min at 25°C in an atmosphere of nitrogen and cell death was measured by nigrosine dye uptake. After 45 min of anoxia and a 4- to 6-hr incubation in normal Ca++- containing media, cells from all segments were dead. Addition of calcium channel blockers verapamil and nifedipine (5 x 10-7 and 10-6 M, respectively) for the first 2 hr after anoxia to the incubation media was associated with a 60 ± 8 and 33 ± 7% survival of PST cells (5 hr arter anoxia), p<.05. Verapamil at 5 x 10-8 M caused a 42 ± 4% survival whereas nifedipine at 10-7 M was not effective on the survival rate of PST cells (5 hr after anoxia). These calcium channel blockers also afforded protection from anoxic cell death for CCT cells. The role of calmodulin in anoxic cell injury was studied by means of calmodulin binding drugs, trifluoperazine and W7 [N-(6-aminohexyl)-5-chloronaphthalene-sulfonamide]. Addition of trifluoperazine (5 x 10-7 M) and W7 (5 x 10-7 M to both PST and CCT cells during the 2-hr reflow period after 45 min of anoxia increased viability by 58 ± 3 and 62 ± 3%, respectively (P<.05) at 5 hr postanoxia. Thus, calcium channels blockers are potent drugs to prevent anoxic injury to cells in culture independent of any vascular action which has to be considered in in vivo conditions. Calmodulin binding drugs are similarly potent in attenuating anoxia-induced cell death.

Original languageEnglish
Pages (from-to)119-124
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume238
Issue number1
StatePublished - 1986
Externally publishedYes

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