Activation of the sympathetic nervous system promotes blood pressure salt-sensitivity in C57BL6/J mice

Ailsa Ralph, Celine Grenier, Hannah Costello, Kevin Stewart, Jess R Ivy, Neeraj Dhaun, Matthew A Bailey

Research output: Contribution to journalArticlepeer-review


Global salt intake averages >8g/person/day, over twice the limit advocated by the American Heart Association. Dietary salt excess leads to hypertension and this partly mediates its poor health outcomes. In ~30% of people, the hypertensive response to salt is exaggerated. This ‘saltsensitivity’ increases cardiovascular risk. Mechanistic cardiovascular research relies heavily on rodent models and the C57BL6/J mouse is the most widely used reference strain. We examined the effects of high-salt intake on blood pressure, renal and vascular function in the most commonly-used and commercially-available C57BL6/J mouse strain . Changing from control (0.3% Na+) to high-salt (3% Na+) diet increased systolic blood pressure in male mice by ~10mmHg within 4 days of dietary switch. This hypertensive response was maintained over the 3-week study period. Returning to control diet gradually reduced blood pressure back to baseline. High-salt diet caused a rapid and sustained downregulation in mRNA encoding renal NHE3 and ENaC although we did not observe a suppression in aldosterone until ~7 days. During the development of salt-sensitivity, the acute pressure-natriuresis relationship was augmented and neutral sodium balance was maintained throughout. High-salt diet increased ex vivo sensitivity of the renal artery to phenylephrine and increased urinary excretion of adrenaline, but not noradrenaline. The acute blood pressure-depressor effect of hexamethonium, a ganglionic blocker, was enhanced by high salt. Salt-sensitivity in commercially-sourced C57BL6/J mice is attributable to sympathetic overactivity, increased adrenaline and enhanced vascular sensitivity to alpha-adrenoreceptor activation, and not sodium retention or attenuation of the acute pressure-natriuresis response. Keywords: salt-sensitivity, hypertension, endothelial function, pressure natriuresis, sympathetic nervous system
Original languageEnglish
Early online date16 Nov 2020
Publication statusE-pub ahead of print - 16 Nov 2020


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