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Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels.
Invest Ophthalmol Vis Sci. 2012 Jun 26; 53(7):4099-110.IO

Abstract

PURPOSE

To investigate the mechanism of the neuroprotective effects of the angiotensin II type 1 receptor (AT1-R) blocker against retinal ischemia-reperfusion injury in the rat.

METHODS

Retinal ischemia was induced by increasing intraocular pressure. Glutamate release from the rat retina and intravitreal PO(2) (partial pressure of oxygen) profiles were monitored during and after ischemia using a microdialysis biosensor and oxygen-sensitive microelectrodes. ELISA was used to measure changes in the expression of AT1-R. Retinal mRNA expressions of p47phox and p67phox were measured by real-time polymerase chain reaction. Reactive oxygen species (ROS) were measured using dihydroethidium.

RESULTS

Administration of candesartan, which is an AT1-R blocker (ARB), suppressed ischemia-induced increases in the extracellular glutamate. Candesartan also attenuated the increase in intravitreal PO(2) during reperfusion. AT1-R expression peaked at 12 hours after reperfusion. Although there was an increase in the retinal mRNA expression of p47phox and p64phox at 12 hours after the reperfusion, administration of candesartan suppressed these expressions. The production of ROS that was detected at 12 hours after reperfusion was also suppressed by the administration of candesartan or apocynin.

CONCLUSIONS

NADPH oxidase-mediated ROS production increased at 12 hours after reperfusion. Candesartan may protect neurons by decreasing extracellular glutamate immediately after reperfusion and by attenuating oxidative stress via a modulation of the AT1-R signaling that occurs during ischemic insult.

Authors+Show Affiliations

Department of Ophthalmology, Kagawa University, Kagawa, Japan. t-fujita@kms.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22661470

Citation

Fujita, Tomoyoshi, et al. "Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1-R) Blocker Via Modulating AT1-R Signaling and Decreased Extracellular Glutamate Levels." Investigative Ophthalmology & Visual Science, vol. 53, no. 7, 2012, pp. 4099-110.
Fujita T, Hirooka K, Nakamura T, et al. Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels. Invest Ophthalmol Vis Sci. 2012;53(7):4099-110.
Fujita, T., Hirooka, K., Nakamura, T., Itano, T., Nishiyama, A., Nagai, Y., & Shiraga, F. (2012). Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels. Investigative Ophthalmology & Visual Science, 53(7), 4099-110. https://doi.org/10.1167/iovs.11-9167
Fujita T, et al. Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1-R) Blocker Via Modulating AT1-R Signaling and Decreased Extracellular Glutamate Levels. Invest Ophthalmol Vis Sci. 2012 Jun 26;53(7):4099-110. PubMed PMID: 22661470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels. AU - Fujita,Tomoyoshi, AU - Hirooka,Kazuyuki, AU - Nakamura,Takehiro, AU - Itano,Toshifumi, AU - Nishiyama,Akira, AU - Nagai,Yukiko, AU - Shiraga,Fumio, Y1 - 2012/06/26/ PY - 2012/6/5/entrez PY - 2012/6/5/pubmed PY - 2012/12/18/medline SP - 4099 EP - 110 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 53 IS - 7 N2 - PURPOSE: To investigate the mechanism of the neuroprotective effects of the angiotensin II type 1 receptor (AT1-R) blocker against retinal ischemia-reperfusion injury in the rat. METHODS: Retinal ischemia was induced by increasing intraocular pressure. Glutamate release from the rat retina and intravitreal PO(2) (partial pressure of oxygen) profiles were monitored during and after ischemia using a microdialysis biosensor and oxygen-sensitive microelectrodes. ELISA was used to measure changes in the expression of AT1-R. Retinal mRNA expressions of p47phox and p67phox were measured by real-time polymerase chain reaction. Reactive oxygen species (ROS) were measured using dihydroethidium. RESULTS: Administration of candesartan, which is an AT1-R blocker (ARB), suppressed ischemia-induced increases in the extracellular glutamate. Candesartan also attenuated the increase in intravitreal PO(2) during reperfusion. AT1-R expression peaked at 12 hours after reperfusion. Although there was an increase in the retinal mRNA expression of p47phox and p64phox at 12 hours after the reperfusion, administration of candesartan suppressed these expressions. The production of ROS that was detected at 12 hours after reperfusion was also suppressed by the administration of candesartan or apocynin. CONCLUSIONS: NADPH oxidase-mediated ROS production increased at 12 hours after reperfusion. Candesartan may protect neurons by decreasing extracellular glutamate immediately after reperfusion and by attenuating oxidative stress via a modulation of the AT1-R signaling that occurs during ischemic insult. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/22661470/Neuroprotective_effects_of_angiotensin_II_type_1_receptor__AT1_R__blocker_via_modulating_AT1_R_signaling_and_decreased_extracellular_glutamate_levels_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.11-9167 DB - PRIME DP - Unbound Medicine ER -