Gender-, strain-, and inheritance-dependent variation in aldosterone secretion in mice

Arterial hypertension represents one of the most common diseases in developed countries and the rennin-angiotensin-aldosterone system is among the major factors in the regulation of blood pressure and sodium balance. With the exception of rare monogenetic diseases, however, inheritance of aldosterone secretion is widely unknown. In this study, we investigated the aldosterone levels in male and female mice of two inbred strains, C3HeB/FeJ and C57BL/6J, as well as their offspring of the F1 and F2 generation. In all cases, female animals displayed lower aldosterone levels than males. Furthermore, C57BL/6J animals had significantly higher aldosterone levels than C3HeB/FeJ mice of the same age and gender. Depending on the paternal origin of the animal, the F1 offspring showed a tendency toward higher aldosterone values when the paternal side was from the C57BL/6J strain. This observation was confirmed in the F2 generation and over repeated measurements over three consecutive years. Quantification of the aldosterone to renin ratio in the different mouse groups did not show any significant differences, and, similarly, the determination of plasma potassium and kidney parameters did not provide any differences. On the molecular level, investigation of the expression of the enzymes involved in steroidogenesis displayed the same trend as for the aldosterone values, with animals hosting C57BL/6J background in their paternal origin having also the highest expression levels for StAR, cyp11a1, and cyp11b2 enzymes. Taken together, we could demonstrate that the genetic background of the animals plays a significant role modulating their plasma aldosterone levels without clear interference of other parameters in the renin-angiotensin-aldosterone system.