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Mechanisms of endothelial dysfunction after ionized radiation: selective impairment of the nitric oxide component of endothelium-dependent vasodilation.

https://arctichealth.org/en/permalink/ahliterature45941
Source
Br J Pharmacol. 2003 Mar;138(5):837-44
Publication Type
Article
Date
Mar-2003
Author
Anatoly I Soloviev
Sergey M Tishkin
Alexander V Parshikov
Irina V Ivanova
Eugene V Goncharov
Alison M Gurney
Author Affiliation
Department for Experimental Therapeutics, Institute of Pharmacology and Toxicology, Academy of Medical Sciences, 14, Eugene Pottier Street, Kiev, 03057 Ukraine.
Source
Br J Pharmacol. 2003 Mar;138(5):837-44
Date
Mar-2003
Language
English
Publication Type
Article
Keywords
Animals
Aorta, Thoracic - drug effects - physiology - radiation effects
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Endothelium, Vascular - drug effects - physiology - radiation effects
In Vitro
Male
Nitric Oxide - physiology - radiation effects
Rabbits
Radiation, Ionizing
Research Support, Non-U.S. Gov't
Vasodilation - drug effects - physiology - radiation effects
Abstract
(1) Gamma radiation impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about radiation effects on other endothelial mediators. (2) This study investigated the mechanisms of endothelial dysfunction in rabbits subjected to whole-body irradiation from a cobalt(60) source. (3) The endothelium-dependent relaxation of rabbit aorta evoked by acetylcholine (ACh) or A23187 was impaired in a dose-dependent manner by irradiation at 2 Gy or above. Inhibition was evident 9 days post-irradiation and persisted over the 30 day experimental period. (4) Endothelium-independent responses to glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1) were suppressed over a similar dose range at 7-9 days post-irradiation, but recovered fully by 30 days post-irradiation. (5) In healthy vessels, ACh-induced relaxation was inhibited by L-N(omega)-nitroarginine (L-NA; 3 x 10(-4) M) and charybdotoxin (10(-8) M) plus apamin (10(-6) M) but resistant to indomethacin, indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). Supporting this, ACh caused smooth muscle hyperpolarization that was reduced by L-NA and charybdotoxin plus apamin. (6) In irradiated vessels, responses to ACh were insensitive to L-NA but abolished by charybdotoxin plus apamin, indicating selective loss of NO-mediated relaxation. (7) In animals treated shortly after irradiation with the antioxidant, alpha-tocopherol acetate, the NO-dependent relaxation was restored without effect on the EDHF-dependent component. (8) The results imply that radiation selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level.
PubMed ID
12642385 View in PubMed
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