To obtain the wisdom for conquering hypertension, in ISH2022KYOTO, we propose three new hypertension research fields, that is, FOOD (nutrition), MOVE (physical fitness) and AI (digital transformation). In 2003, I propose the clinical concept of “Metabolic Domino”, which illustrates the whole picture of non-communicable diseases (NCDs), including hypertension, beginning from derangement of lifestyle (FOOD and MOVE) and deposition of visceral fat. 1) FOOD: In 2022, we elucidate the important role of the kidney and intestines which (re)absorb sugar and salt “greedily” by the activation of “greedy genes,” the genes to be activated by excessive sugar and salt, including SGLT (sodium-glucose co-transporter)1,2 and MR (mirenalocorticoid receptor) genes, and cause hypertension/CKD and obesity/diabetes mellitus (“Greedy Organ Hypothesis”). Overactivation of MR by salt or sugar induces “MR-associated hypertension” with wide range of plasma aldosterone level. 2) MOOVE: By exercise, the increase of blood shear stress and heat rate induces the secretion of nitric oxide or natriuretic peptides, which not only reduce blood pressure but also activate mitochondria in the skeletal muscle to prevent sarcopenia and obesity. Angiotensin II has the opposite metabolic actions. 3) AI: The time-course of Metabolic Domino is now highlighted. Pre-emptive medicine or “Me-byo” (“Not-yet disease”) medicine intervenes the most upstream of Metabolic Domino to prevent occurrence of the disease. We demonstrated the transient early blockade of renin-angiotensin system can achieve prevention or regression of hypertension in experimental animals and suggested the possibility in humans. The treatment memory is mediated the alteration of epigenetic status of the organs (e.g. the kidney or blood vessels) (“Organ Memory”2018). Angiotensin II exerts modulatory effect on epigenetic change. Big data science with advanced digital technology for monitoring biorhythm data, such as blood pressure, blood glucose level, sympathetic tone or sleep depth, and also alteration of the life-environment, we will predict the specific trajectory of each individual with elevated blood pressure, and can modify organ memory and modulate the future outcome. By these innovative approaches, I will expect the establishment of the community in which no one with hypertension is left behind to serve for sustainable well-being.
