Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism

Human primary aldosteronism (PA) can be caused by mutations in several ion channel genes but mouse models replicating this condition are lacking. We now show that almost all known PA-associated CLCN2 mutations markedly increase ClC-2 chloride currents and generate knock-in mice expressing a constitutively open ClC-2 Cl− channel as mouse model for PA. The Clcn2op allele strongly increases the chloride conductance of zona glomerulosa cells, provoking a strong depolarization and increasing cytoplasmic Ca2+ concentration. Clcn2op mice display typical features of human PA, including high serum aldosterone in the presence of low renin activity, marked hypertension and hypokalemia. These symptoms are more pronounced in homozygous Clcn2op/op than in heterozygous Clcn2+/op mice. This difference is attributed to the unexpected finding that only ~50 % of Clcn2+/op zona glomerulosa cells are depolarized. By reproducing essential features of human PA, Clcn2op mice are a valuable model to study the pathological mechanisms underlying this disease.

Histological characteristics of accessory adrenal glands of rabbits with different types of autonomous tonus

For the purposes of the adrenal gland’s study, 27 four months old male rabbits (Oryctolagus cuniculus) of Termond White breed were selected. Based on electrocardiography and variation pulsometry results, three types of autonomous tonus were determined in animals: sympathicotonia (ST), normotonia (NT) and parasympathicotonia (PS), which formed the basis for the division of animals into three groups. All rabbits were subjected to euthanasia and histological preparations were made from their adrenal glands. Apart from the main adrenal gland, accessory adrenal gland was detected in five purposes animals, including three ST rabbits, one NT rabbit and one PS rabbit. Also, four accessory adrenal glands were revealed in one ST rabbit simultaneously. In fact, these accessory adrenal glands became the main object of the further morphological research. The obtained historical indicators accessory adrenal glands were compared to the ones from various animal groups (CT with NT and CT with PS), as well as to the indicators of the main adrenal gland in each group. Statistical analysis of the received data was performed only in the group of ST animals. Accessory adrenal gland of ST rabbits is represented by two zones: zona glomerulosa and zona fasciculata, the area of which is 52% and 48% respectively. In PS and NT rabbits, the glands are formed by zona glomerulosa only. Investigating the accessory adrenal gland’s cellular component, it was found that NT rabbits have the largest cell area in zona glomerulosa, while PS rabbits have the smallest one. At the same time, the area of nucleus has the largest values in ST animals and the smallest ones in PS animals likewise. Сomparing zona glomerulosa and zona fasciculata in ST rabbits, it was found that cell size differs significantly, while the area of nucleus is almost identical. The nuclear-cytoplasmic ratio in zona glomerulosa cells is the largest for PS rabbits. The smallest ratio values were detected among the NT rabbits. Obviously, ST rabbits occupy an intermediate position. Unlike the main adrenal gland, the cells of accessory adrenal gland are of a smaller size and а denser location of cells in all groups of animals. The conducted studies allow concluding that the typological features of the autonomous tonus affect the morphology of accessory adrenal gland.