Time-dependent protective effects of calcium channel blockers on anoxia- and hypoxia-induced proximal tubule injury

Details

Serval ID
serval:BIB_6E56FAF76F79
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Time-dependent protective effects of calcium channel blockers on anoxia- and hypoxia-induced proximal tubule injury
Journal
Journal of Pharmacology and Experimental Therapeutics
Author(s)
Almeida  A. R., Bunnachak  D., Burnier  M., Wetzels  J. F., Burke  T. J., Schrier  R. W.
ISSN
0022-3565 (Print)
Publication state
Published
Issued date
02/1992
Volume
260
Number
2
Pages
526-32
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Abstract
The effects of anoxia or hypoxia on Ca++ uptake and lactic dehydrogenase (LDH) release were examined in freshly isolated rat proximal tubules (rPT). Both Ca++ uptake and LDH release were increased above control after only 10 min of either anoxia or hypoxia in rPT. The increase in Ca++ uptake was through voltage-sensitive, slow Ca++ channels, because pretreatment with chemically dissimilar calcium channel blockers (CCB), either verapamil or flunarizine, prevented the increased Ca++ uptake and reduced the LDH release from the anoxic and hypoxic rPT. After 20 min of hypoxia, however, verapamil pretreatment did not significantly reduce the high Ca++ uptake rate, thus, suggesting that this increase in Ca++ permeability was occurring through pathways other than the slow Ca++ channels. The increase in LDH release was only slightly decreased by verapamil after 20 min of hypoxia. After 20 min of anoxia in rPT, Ca++ uptake was no longer increased, but the increased LDH release persisted. These effects of anoxia were unaltered by verapamil. These results, thus, suggest that early membrane injury to isolated rPT in suspension, which is associated with 10 min of either anoxia or hypoxia, involves increased cellular Ca++ uptake through voltage-sensitive Ca++ channels and protection is afforded by CCB. In contrast, after 20 min of anoxia or hypoxia, rPT membrane damage persisted and was only partially reversed by CCB. The rPT injury induced by 20 min of O2 deprivation, thus, involves factors independent of voltage-sensitive Ca++ channels.
Keywords
Animals Calcium/metabolism Cations, Divalent Flunarizine/*pharmacology Kidney Tubules, Proximal/*drug effects/metabolism L-Lactate Dehydrogenase/metabolism Male Oxygen/*metabolism Rats Rats, Inbred Strains Verapamil/*pharmacology
Pubmed
Web of science
Create date
25/01/2008 12:56
Last modification date
20/08/2019 14:27
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