Losartan Chemistry and Its Effects via AT1 Mechanisms in the Kidney

Besides the importance of the renin-angiotensin system (RAS) in the circulation and other organs, the local RAS in the kidney has attracted a great attention in research in last decades. The renal RAS plays an important role in the body fluid homeostasis and long-term cardiovascular regulation. All major components and key enzymes for the establishment of a local RAS as well as two important angiotensin II (Ang II) receptor subtypes, AT1 and AT2 receptors, have been confirmed in the kidney. In addition to renal contribution to the systemic RAS, the intrarenal RAS plays a critical role in the regulation of renal function as well as in the development of kidney disease. Notably, kidney AT1 receptors located at different cells and compartments inside the kidney are important for normal renal physiological functions and abnormal pathophysiological processes. This mini-review focuses on: 1) the local renal RAS and its receptors, particularly the AT1 receptor and its mechanisms in physiological and pathophysiological processes, and 2) the chemistry of the selective AT1 receptor blocker, losartan, and the potential mechanisms for its actions in the renal RAS-mediated disease.