Arginine Metabolism in Hypertensive Rats under Arginase Inhibition by Norvaline

The hypotensive effect of arginase inhibition [1] can be achieved experimentally in two ways: by increasing the nitric oxide ( NO) concentration that causes vasorelaxation, and/or by decreasing the circulating fluid volume. The first way occurs with an increase in the availability of the NO synthase (NOS) substrate arginine (ARG), while the second can be implemented with an increase in diuresis. To define more exactly the ways in which arginase affects arterial blood pressure (BP) regulation, we analyzed the metabolic characteristics of the amino acid L-arginine in hypertensive (ISIAH strain) and normotensive (WAG strain) rats under the inhibition of arginase activity by L-norvaline. Concentrations of ARG and its metabolite ornithine were measured in blood, urine, and kidney tissue homogenates using high-performance liquid chromatography with the separation on a reversed-phase sorbent and fluorescence detection. Norvaline was administered intraperitoneally (i.p.) once a day at a dose of 30 mg/kg for 7 days. Norvaline caused no significant changes in the blood concentration of amino acids in both normotensive and hypertensive rats. After norvaline administration, the urine ARG concentration in normotensive rats remained intact, but increased twofold in hypertensive rats. Daily ARG excretion in norvaline-treated normotensive rats increased quite insignificantly, but in hypertensive rats increased under the same conditions almost threefold, with diuresis being increased in hypertensive rats only. Under the effect of norvaline, the ARG content per 1 g of kidney weight was intact in normotensive rats but increased almost twofold in hypertensive rats. Our data indicate that arginase inhibition by norvaline had a stronger hypotensive effect on hypertensive rather than normotensive rats. At the same time, in normotensive rats, the hypotensive effect of norvaline may be provided by the NO system, while in hypertensive rats, it seems to be realized through enhanced diuresis.