Acute salt loading induces sympathetic nervous system overdrive in mice lacking salt-inducible kinase 1 (SIK1)

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Pires, NM (Author) Other; Igreja, B (Author) Other; Maria Paula Serrão (Author) FMUP; Matias, EF (Author) FMUP; Moura, E (Author) Other; Antonio, T (Author) Other; Campos, FL (Author) Other; Brion, L (Author) Other; Bertorello, A (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: Hypertension Research

Vol. 42

Pages: 1114-1124

ISSN: 0916-9636

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00Q-C4Y

DOI: 10.1038/s41440-019-0249-z

Abstract (EN): 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-angiotensin-aldosterone 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 beta-hydroxylase (D beta H), 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 beta H 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11