Aldose reductase inhibitors improve myocardial reperfusion injury in mice by a dual mechanism
(2006) In Journal of Pharmacological Sciences 102(1). p.37-46- Abstract
- Aldose reductase (AR) has been implicated in the pathogenesis of diabetic complications, although the clinical efficacy of AR inhibitors has not been clearly proven. To clarify the pathophysiological role of AR in the heart, we investigated effects of AR inhibitors applied either during the pre-ischemic phase, or during the post-ischemic reperfusion phase on ischemia-reperfusion injury in isolated heart from transgenic mice overexpressing human AR. On reperfusion following global ischemia, transgenic mouse hearts exhibited lower left developed pressure, increased release of creatine kinase, and lower ATP content compared with their littermates. When inhibitors of AR were applied during the pre-ischemic phase, they significantly improved... (More)
- Aldose reductase (AR) has been implicated in the pathogenesis of diabetic complications, although the clinical efficacy of AR inhibitors has not been clearly proven. To clarify the pathophysiological role of AR in the heart, we investigated effects of AR inhibitors applied either during the pre-ischemic phase, or during the post-ischemic reperfusion phase on ischemia-reperfusion injury in isolated heart from transgenic mice overexpressing human AR. On reperfusion following global ischemia, transgenic mouse hearts exhibited lower left developed pressure, increased release of creatine kinase, and lower ATP content compared with their littermates. When inhibitors of AR were applied during the pre-ischemic phase, they significantly improved deranged cardiac function, creatine kinase release, and ATP content. On the other hand, inhibition of AR during the post-ischemic reperfusion phase did not affect cardiac performance and ATP content, but it significantly attenuated creatine kinase release and the level of thiobarbiturate-reactive substances in transgenic mouse hearts. These results suggest a dual role of AR in ischemia-reperfusion injury. Inhibition of AR during ischemia preserved generation of ATP via glycolysis, whereas inhibition during the reperfusion phase reduced myocardial injury by attenuating oxidative stress elicited by ischemic insult and reoxygenation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/389502
- author
- Iwata, Kazumi ; Matsuno, Kuniharu ; Nishinaka, Toru ; Persson, Christina LU and Yabe-Nishimura, Chihiro
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- polyol pathway, ischemia-reperfusion injury, aldose reductase, heart, sorbitol dehydrogenase
- in
- Journal of Pharmacological Sciences
- volume
- 102
- issue
- 1
- pages
- 37 - 46
- publisher
- Japanese Pharmacological Society
- external identifiers
-
- pmid:16936455
- wos:000240882600008
- scopus:33748954996
- ISSN
- 1347-8648
- DOI
- 10.1254/jphs.FP0060218
- language
- English
- LU publication?
- yes
- id
- 8d03c09a-4d99-4547-ba8c-498e86eecf69 (old id 389502)
- date added to LUP
- 2016-04-01 11:58:11
- date last changed
- 2022-01-26 20:55:03
@article{8d03c09a-4d99-4547-ba8c-498e86eecf69,
abstract = {{Aldose reductase (AR) has been implicated in the pathogenesis of diabetic complications, although the clinical efficacy of AR inhibitors has not been clearly proven. To clarify the pathophysiological role of AR in the heart, we investigated effects of AR inhibitors applied either during the pre-ischemic phase, or during the post-ischemic reperfusion phase on ischemia-reperfusion injury in isolated heart from transgenic mice overexpressing human AR. On reperfusion following global ischemia, transgenic mouse hearts exhibited lower left developed pressure, increased release of creatine kinase, and lower ATP content compared with their littermates. When inhibitors of AR were applied during the pre-ischemic phase, they significantly improved deranged cardiac function, creatine kinase release, and ATP content. On the other hand, inhibition of AR during the post-ischemic reperfusion phase did not affect cardiac performance and ATP content, but it significantly attenuated creatine kinase release and the level of thiobarbiturate-reactive substances in transgenic mouse hearts. These results suggest a dual role of AR in ischemia-reperfusion injury. Inhibition of AR during ischemia preserved generation of ATP via glycolysis, whereas inhibition during the reperfusion phase reduced myocardial injury by attenuating oxidative stress elicited by ischemic insult and reoxygenation.}},
author = {{Iwata, Kazumi and Matsuno, Kuniharu and Nishinaka, Toru and Persson, Christina and Yabe-Nishimura, Chihiro}},
issn = {{1347-8648}},
keywords = {{polyol pathway; ischemia-reperfusion injury; aldose reductase; heart; sorbitol dehydrogenase}},
language = {{eng}},
number = {{1}},
pages = {{37--46}},
publisher = {{Japanese Pharmacological Society}},
series = {{Journal of Pharmacological Sciences}},
title = {{Aldose reductase inhibitors improve myocardial reperfusion injury in mice by a dual mechanism}},
url = {{http://dx.doi.org/10.1254/jphs.FP0060218}},
doi = {{10.1254/jphs.FP0060218}},
volume = {{102}},
year = {{2006}},
}