EFFECT OF HIGH NaCl DIET ON HEPATIC Na^+ RESEPTOR SENSITIVITY AND EXPRESSION OF NKCC1 IN RATS

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・ We previously reported that the bumetanide-sensitive Na^+-K^+-2Cl^- cotransporter (NKCC1) is involved in the hepatic Na^+ and K^+ sensor mechanism. In the present study, we examined the effects of a high NaCl or high KCl diet on hepatic Na^+ and K^+ receptor sensitivity and NKCC1 expression in the liver of Sprague-Dawley rats. RT-PCR and Western blots were used to measure NKCC1 mRNA and protein expression, respectively. Infusion of hypertonio NaCl or isotonic KCl + NaCl solutions into the portal vein increased hepatic afferent nerve activity (HANA) in a Na^+ or K^+ concentration-dependent manner. After 4 weeks on a high NaCl or high KCl diet, HANA responses were attenuated compared to in animals fed a normal diet, and NKCC1 expression was reduced. These results show that a high NaCl or high KCl diet decreases NKCC1 expression in the liver and it causes a reduction in hepatic Na^+- and K^+-receptor sensitivity.・ It is well known that an intra-cerebroventricular injection of hypertonio … More NaCl elicits an increase in arterial pressure through activation of sympathetic nervous system and vasopressin. However, the central pathway of this response is not clear, because of diffusion of injected NaCl throughout the brain and a difficulty in detecting activated brain regions with reasonable spatial and temporal resolutions. Recently, we have reported the usefulness of Mn^<2+> contrasted magnetic resonance imaging (MRI) in hypothalamic imaging. In this method, following the triggering of action potential, Ma^<2+> eaters the intracellular space through Ca^<2+> pathways. Thus, activated neuronal cells contain more Mn^<2+>, which results in an increased signal intensity in T_1-weighted MRI. In the present study, the central activation in response to an intra-lateral ventricular injection of hypertonic NaCl (1.5 M, 10 μl) was detected using this technique in anesthetized rats. The peri-ventricular region was first activated, and activated regions moved into the brain parenchyma. The time course of the central activation was comparable to time course of arterial pressure and sympathetic nerve activity responses. Less