Adaptation of C57BL/6J Mice to High Dietary Salt

Abstract

Our habitually high salt intake has a detrimental relationship with blood pressure (BP); the more salt consumed per day, the higher the incidences of hypertension within the population (Meneton et al., 2005). This substantial BP effect is an important modifiable risk factor for cardiovascular and renal disease, however the underlying mechanisms responsible remain controversial. Vasodysfunction is proposed as a key event, as the normal decrease in systemic vascular resistance (SVR) is attenuated in salt‐sensitive human subjects (Morris et al., 2016), suggesting impaired vasodilation. Other main theories include a salt‐induced suppression of the acute pressure natriuresis (PN) relationship, in which renal sodium (Na) excretion does not appropriately increase to offset elevated perfusion pressure and rebalance extracellular fluid volume (Hall, 2016). Thus the current study aimed to investigate BP, vasodilatory and PN responses in adult male C57BL/6J mice fed a high salt diet. In the first experiment, mice (n=6–7) had radiotelemetry devices implanted to allow the continuous recording of BP. After 1 week of a standard (0.3% Na) salt intake, mice were fed high salt (3% Na) for a further week. Systolic BP increased significantly by 10.5mmHg during high salt feeding. Next, mice were fed either a standard or high salt diet for 1 week before culling to measure plasma aldosterone and vascular reactivity via isolating mesenteric arteries and administering vasodilatory agents acetylcholine and sodium nitroprusside by wire myography. Plasma aldosterone was substantially lower in mice on the high salt diet. No evidence of intrinsic vasodysfunction was observed: sensitivity to both acetylcholine and sodium nitroprusside did not differ between dietary groups. In the third and final experiment, mice were fed a standard (n=7) or high (n=6) salt diet for 1 week and the acute PN response was measured. This generated a curve expressing the relationship between BP and urinary Na excretion. Mice were anaesthesised with Inactin (120mg/kg) and major arteries were ligated to acutely increase BP. Urine was collected via a bladder catheter. In both groups, there was a significant increase in urinary Na excretion with increasing BP. Glomerular filtration rate (GFR) and renal blood flow also increased, with no differences between cohorts observed. The PN curve was shifted to the left, with a steeper gradient in mice fed high salt compared to those on the standard diet. To conclude, this study reports a salt‐induced increase in BP in C57BL/6J mice. There is no evidence for isolated vasodysfunction, and appropriate adaptation of the renin‐angiotensin‐aldosterone system and the acute PN response was seen to salt challenge. Since BP is a product of cardiac output and SVR, which in turn is influenced by vascular tone, current studies are investigating the contribution of these haemodynamic parameters.Support or Funding InformationThis research was funded by the University of EdinburghThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.