Метаболизм L-аргинина у гипертензивных крыс при угнетении аргиназы L-норвалином

Abstract

The hypotensive effect of arginase inhibition in the experiment [1] can be realized in two ways: by relaxation of blood vessels by an increase in the concentration of nitric oxide (NO) and/or a decrease in the amount of circulating fluid. The first effect occurs with an increase in the availability of the substrate of NO synthase (NOS) - arginine (ARG). The second - with an increase in diuresis. To clarify the ways in which arginase affects the regulation of blood pressure (BP) we have analyzed the metabolic characteristics of the amino acid L-arginine in hyper- and normotonic rats during inhibition of arginase activity by the administration of its inhibitor L-norvaline. The concentration of arginine and its metabolite ornithine in blood, urine, and in the homogenate of kidney tissue was measured using high-performance liquid chromatography with the separation on a reversed-phase sorbent and with a fluorescence detection. Norvaline was injected intraperitoneally (ip) once a day at a dose of 30 mg/kg for 7 days. In experiments under the influence of norvaline, no significant increase in the concentration of amino acids in the blood plasma was found either in hypertensive rats (ISIAH strain) or in normotensive control (WAG strain). The concentration of arginine in the urine of ISIAH animals treated with norvaline was found doubled, while in WAG rats it did not change. The daily excretion of arginine under norvaline increased in normotonics only slightly, and in hypertensive rats it increased almost threefold. At the same time, norvaline increased diuresis only in hypertensive animals. Under the influence of norvaline, the content of arginine per 1 g of kidney weight increased almost twofold in hypertensive rats, while in normotensive rats it did not change. The studies performed allow us to conclude, that inhibition of arginase by norvaline had a stronger hypotensive effect in hypertensive rats than in normotensive rats. At the same time, the hypotensive effect of norvaline in normotonic rats can be provided by the nitric oxide system, whereas in hypertensive rats this function is taken over by diuresis.