Investigating the renal and vascular mechanisms of salt-induced hypertension in C57BL6/J mice
Item statusRestricted Access
Embargo end date30/11/2021
Ralph, Ailsa Florence
Dietary salt intake has a detrimental relationship with blood pressure (BP); the more salt consumed per day, the higher the incidence of hypertension and its cardiorenal consequences within a population. However, the underlying mechanisms responsible remain controversial. Research supports roles for both the kidneys and the vasculature in salt-induced hypertension. Here, I investigated the effect of a high salt diet (HSD) on BP, renal function and the vascular responses to vasoconstrictors and vasodilators in adult male C57BL6/JCrl mice. In my experiments, mice were fed either a HSD (3% sodium) or a standard salt (0.25% sodium) diet (SSD). BP was measured in conscious, freely moving animals by radiotelemetry. After measurements on the SSD, mice were fed the HSD and BP increased by ~5mmHg after 3-4 days and remained elevated for up to 3 weeks. Plasma aldosterone concentration was suppressed after 1 week HSD. Assessment of the acute pressure natriuresis (PN) response under anaesthesia illustrated increased urinary sodium excretion at any given BP and messenger RNA (mRNA) levels of some key renal sodium transporters were appropriately decreased by the HSD. Isolated renal arteries displayed increased sensitivity to the vasoconstrictor phenylephrine after 1 week of high salt. In mesenteric arteries, no functional changes were observed to the HSD, supported by no changes in endothelial NO synthase mRNA levels compared to the SSD. Urinary catecholamine concentration was used as an index of sympathetic nerve system (SNS) activity. Adrenaline excretion increased significantly on the HSD, indicating SNS involvement. To test this, the ganglionic blocker hexamethonium was administered via intraperitoneal injection and the resulting transient dip in BP was modestly increased and persisted after 3 weeks of the HSD. In conclusion, I observed a sustained salt-induced increase in BP in C57BL6/JCrl mice. Appropriate adaptation of aldosterone production and the acute PN response to salt challenge was seen. Increased excretion of adrenaline, elevated contractility of renal arteries and a greater effect on SBP with hexamethonium suggests over-activity of the SNS is an important factor in salt-induced hypertension in C57BL6/JCrl mice.