Modification of Radiation Injury by Ramipril, Inhibitor of Angiotensin-Converting Enzyme, on Optic Neuropathy in the Rat

Jae Ho Kim, Stephen L. Brown, Andrew Kolozsvary, Kenneth A. Jenrow, Samuel Ryu, Mark L. Rosenblum, Oscar A. Carretero

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Inhibitors of angiotensin-converting enzyme (ACE) have been used to reduce radiation-induced normal tissue injury. The present study was carried out to determine whether ramipril, one of the inhibitors of ACE, would ameliorate radiation-induced brain damage, using a well-characterized optic neuropathy model in the rat, one of the most critical and radiosensitive structures in the brain. The brains of adult Fischer rats were irradiated stereotactically with 30 Gy using a single collimated beam. Six months after irradiation and 1.5 mg/ kg day-1 ramipril (started 2 weeks after irradiation), rats were assessed for optic nerve damage functionally, using visual evoked potential, and histologically. Results show that ramipril conferred significant modification of radiation injury, since rats receiving radiation alone showed a threefold lengthening in the mean peak latency in the visual evoked potential, whereas 75% of rats receiving radiation followed by ramipril had evoked potentials that resembled those of normal untreated control rats. The histology of irradiated and ramipril-treated optic nerves appeared nearly normal, while there was significant demyelination in both optic nerves of irradiated rats. The study represents the first demonstration of prophylaxis of radiation injury by a carboxyl-containing ACE inhibitor, providing a pharmacological strategy designed to reduce radiation-induced normal tissue damage.

Original languageEnglish
Pages (from-to)137-142
Number of pages6
JournalRadiation Research
Volume161
Issue number2
DOIs
StatePublished - Feb 2004

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