CENTRAL NEUROCHEMICAL MECHANISMS OF ANTIPYRETIC ACTION OF L-ARGININE UNDER ENDOTOXIN FEVER CONDITIONS

The experiments on rats and rabbits using modern physiological, biochemical methods of research and pharmacological approach have shown that arginine of blood plasma and liquor participates in central neurochemical mechanisms of thermoregulation during endotoxin fever, changing the chemoreactive properties of cerebral neurons and the impulsive activity of heat-sensitive neurons brain thermoregulatory structures. It has been established that the administration of L-arginine hydrochloride into the brain ventricles at a dose of 100 μg per animal or into the blood stream at a dose of 20 mg/ kg causes the pronounced antipyretic effect. In 30 minutes after the intravenous administration of carbon-labeled arginine hydrochloride (25 μCi/kg) at the height of endotoxin fever (60 minutes after the injection of endotoxine E. coli), the radioac tivity level in the blood plasma decreases and significantly increases in cerebrospinal fluid and hypothalamus tissue in rabbits. It has been revealed that although the content and speed of norepinephrine turnover in the hypothalamus after the introduction of L-arginine hydrochloride (100 μg) into the ventricles of the rats does not change in comparison with control animals, however, the chemoreactive properties of the thermoregulatory structures of the brain change, which manifests itself in a change in the expression and duration of thermoregulatory effects of the central action of norepinephrine and acetylcholine. It has been found that L-arginine hydrochloride (100 μg) after being introduced into the brain ventricles stimulates the growth of the impulse activity of heat-sensitive neurons of the medial preoptic region of the anterior hypothalamus in rabbits, caused by an increase in the brain temperature when the animal body is overheated. Apparently, the basis of one of the mechanisms of the antipyretic action of arginine under endotoxin fever conditions is the change in adreno- and cholinoreactive properties of cerebral neurons and, in particular, the increase in the sensitivity of brain adrenoretseptors to noradrenaline. 

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