Renin-angiotensin-aldosterone system and its relation to hypertension

Regulation of the renin-angiotensin-aldosterone system plays an important role in the onset and progression of hypertension. In this system, there are two types of angiotensin II (Ang II) receptors: type 1 (AT₁) and type 2. Pathological effects such as high blood pressure and cardiac hypertrophy are generally mediated by AT₁ receptor. Therefore, direct renin inhibitors, angiotensin-converting enzyme inhibitors, AT₁ receptor blockers, angiotensin receptor-neprilysin inhibitors, and mineralocorticoid receptor antagonists have been developed to suppress these adverse effects. We have been studying this field since the 1990s. When the AT₁ receptor is activated, its structure changes and various signals are transmitted into the cell. AT₁ receptor blockers suppress this change in the structure of the receptor and inhibit intracellular signals. Recent studies have focused on the development of biased ligands that do not inhibit all intracellular signals, and instead inhibit only some adverse signals and activate necessary signals. New therapeutic drugs that are not AT₁ receptor blockers but are mediated by AT₁ receptor may be developed. Therefore, we mainly review the structure and function of the AT₁ receptor, as well as the roles of its blockers or inhibitors and biased ligands, including their role in the prevention of cardiometabolic syndrome including hypertension.