**9. Finally, low-salt diet may protect our brain**

As vertebrates evolved from the sea to the land, they developed the RAAS system and came to have a Na+ retention system that could withstand desiccation and dehydration.

Furthermore, humans began to develop a taste for salt, finding it delicious in their meals. With the increase in industrial production of cheap NaCl, excessive

#### **Figure 3.**

*Our hypothesis: Excess salt in gut induced hypertension and brain damage in a deterioration spiral manner among three systematic dysregulation of Na+ homeostasis.*

*Hypertension as Three Systematic Dysregulations of Na+ Homeostasis in Terrestrial Mammal… DOI: http://dx.doi.org/10.5772/intechopen.98904*

salt intake first became possible, causing hypertension and hypertensive diseases such as stroke. Furthermore, it has very recently been pointed out that excess salt can trigger dysbiosis of the intestinal microflora, which can lead to autoimmune brain diseases. In this study, we clarified that three mechanisms that maintain Na+ homeostasis (the circulating plasma Na+ system (AngII-eNOS axis), the total Na+ retention system in body (Aldosterone-ENaC axis), and the tissue Na+ sensing system (TonEBP (in macrophage)-VEGF-C axis) are impaired in salt-sensitive hypertension (**Figure 3**).

In the brain, which is the command center of Na+ homeostasis in vivo, excessive salt causes cerebral blood flow (CBF) decrease because of NOS dysfunction. Secondly, ENaC dysfunction in taste cells causes taste disorder, which leads to a preference for strong salt tastes. In addition, the increase in CSF Na+ leads to the activation of tissue macrophages in the brain (microglia) via TonEBP activation, which causes inflammation in the brain. Thus, we pointed out that the same molecular biological mechanism that leads to the development of salt-sensitive hypertension may also lead to brain toxicity in the form of exacerbation of salt preference (toxicity), emotional instability (CBF decrease), and pathological brain remodeling (structural damage in the brain such as atrophy). Excess salt may also lead to further development of acquired salt-sensitive organ damage through epigenetics. Therefore, we would like to emphasize that it is extremely important to be aware of salt reduction in our daily diet.
