Endocrine Abstracts

The pathway from aldosterone to upregulation of renal sodium re-absorption via the amiloride sensitive sodium channel (ENaC) is strongly implicated in blood pressure control and causation of hypertension (HT) in humans. In order to study these processes further an animal model is required to correlate physiological changes as hypertension develops with the molecular pathways underpinning these in kidney. Transgenic studies indicate mouse is an excellent species for modeling these aspects of human physiology. Thus, we have developed a mineralocorticoid excess model allowing us to precisely induce hypertension via aldosterone in mice.
Adult male C57BL6 mice were uninephrectomised, fed diets with a range of sodium contents and treated with s.c. aldosterone infusion. Blood pressure was assessed by tail-cuff plethysmography. This allowed a precise induction of degrees of hypertension. Compared to control mice (BP 113.7 +/- 1 mmHg: mean +/- SE, n>30), there was a trivial rise in BP after uninephrectomy alone (117.5 +/- 1 mmHg) or a 10 fold increase in dietary sodium to 3% (118.2 +/- 1 mmHg, n=5). However, blood pressure increased significantly (15-30 mmHg) on commencing aldosterone treatment (150 micrograms/kg/d) in groups of uninephrectomised mice (n=5-6) on raised Na+ diets (1-3%): [(1% diet, 114.5 +/- 1 mmHg), (2% diet, 132.5 +/- 2.0 mmHg), (3% diet, 143.2 +/- 2.5 mmHg)]. With higher aldosterone dose the blood pressure rise was steeper.
In conclusion there is development of substantial HT (30 mmHg, p<0.0001) over 21 days with this mouse model allowing the definition of consistent physiological phases relating to BP, fluid balance and other parameters. Additionally significant hypertension was not dependent on a two renin mouse genotype. Thus this represents a useful and robust model for examination of molecular pathways underpinning the physiological phases in development and maintenance of hypertension.