Hypertension as Three Systematic Dysregulations of Na⁺ Homeostasis in Terrestrial Mammal, and Salt in Gut Might Cause Brain Inflammation

Although Na+ homeostasis in vivo is essential for mammals, it is known that excessive salt (NaCl) intake has played a major role in the development of hypertension. In vivo, there is a hormonal system, the renin-angiotensin-aldosterone system (RAAS), that specializes in regulating Na+ retention, especially the amount of Na+ in plasma. Na+ homeostasis in vivo has been achieved mainly by the RAAS, through regulation of vascular tonus (blood pressure) and Na+ handling in the kidney (Na+ diuresis). Recent studies have revealed a third mechanism of Na+ homeostasis in vivo: regulation of interstitial Na+ levels in tissues, such as subcutaneous tissues, by tissue macrophage immunity. In the pathogenesis of salt-sensitive hypertension, Recent research have been revealed that three molecular axes (Ang II - Rho/NOX-eNOS system, Aldosterone-rac1 -ENaC system, and tissue Na+ − TonEBP in macrophage -VEGF-c) are significantly involved in maintaining Na+ homeostasis in salt induced hypertension. Furthermore, the mechanism by which salt causes hypertension via the immune system (intestinal, local mucosal, and tissue immunity) has also been reported. In this article, we would like to propose that three molecular dysfunctions are involved in the development of salt-sensitive hypertension through three immunological mechanisms in the maintenance of Na+ homeostasis. Next, I would like to explain the importance of gut-RAAS and abnormality of intestinal microflora (dysbiosis) in salt-sensitive hypertension. It has been known that the metabolites (e.g., short-chain fatty acid neural amino) produced by microflora are deeply involved in central (CNS) and sympathetic nervous system (SNS) activity. In addition, we would like to explain of the importance of brain-RAAS and cerebral inflammation in salt-sensitive hypertension. Moreover, recent research have revealed that the detection-mechanism in the brain for Na+ concentration([Na+]) in vivo and in the tongue for [Na+] in diet. These finding suggests that excessive salt intake may cause brain dysfunction, most delicate organ, before the onset of salt sensitive hypertension, and may also destroy brain structure after the onset of salt sensitive hypertension. Thus, we would like to insist that excessive salt intake might not only induce hypertension, but also be toxic especially for brain. Finally, we would like to explain that The DASH diet (Dietary Approaches to Stop Hypertension) is one of the universal diets for adult human, not only by reducing salt, but also by reducing metabolic stress and improving of dysbiosis