%0 Journal Article
%T Acute salt loading induces sympathetic nervous system overdrive in mice lacking salt-inducible kinase 1 (SIK1)
%J -
%D 2019
%R https://doi.org/10.1038/s41440-019-0249-z
%X Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic high-salt intake in mice. Here, we further addressed the possible early mechanisms that may relate to the observed rise in BP in mice lacking SIK1. SIK1 knockout (sik1£¿/£¿) and wild-type (sik1+/+) littermate mice were challenged with either a high-salt (8% NaCl) or control (0.3% NaCl) diet for 7 days. Systolic BP was significantly increased in sik1£¿/£¿ mice after 7 days of high-salt diet as compared with sik1+/+ mice and to sik1£¿/£¿ counterparts on a control diet. The renin¨Cangiotensin¨Caldosterone system and the sympathetic nervous system were assayed to investigate possible causes for the increase in BP in sik1£¿/£¿ mice fed a 7-day high-salt diet. Although no differences in serum renin and angiotensin II levels were observed, a reduction in aldosterone serum levels was observed in mice fed a high-salt diet. Urinary L-DOPA and noradrenaline levels were significantly increased in sik1£¿/£¿ mice fed a high-salt diet as compared with sik1£¿/£¿ mice on a control diet. Similarly, the activity of dopamine ¦Â-hydroxylase (D¦ÂH), the enzyme that converts dopamine to noradrenaline, was significantly increased in the adrenal glands of sik1£¿/£¿ mice on a high-salt intake compared with sik1+/+ and sik1£¿/£¿ mice on a control diet. Treatment with etamicastat (50£¿mg/kg/day), a peripheral reversible D¦ÂH inhibitor, administered prior to high-salt diet, completely prevented the systolic BP increase in sik1£¿/£¿ mice. In conclusion, SIK1 activity is necessary to prevent the development of salt-induced high blood pressure and associated SNS overactivity
%U https://www.nature.com/articles/s41440-019-0249-z