Recent Advances in Understanding the Molecular Pathophysiology of Angiotensin II Receptors; Lessons from Cell-Selective Receptor Deletion in Mice.

The renin-angiotensin system (RAS) is an essential hormonal system involved in water and sodium reabsorption, renal blood flow regulation, and arterial constriction. Systemic stimulation of the RAS with infusion of the main peptide angiotensin II (Ang II) in animals as well as pathological elevation of renin (i.e renovascular hypertension) to increase circulatory Ang II in humans ultimately lead to hypertension and end-organ damage. In addition to hypertension, accumulating evidence support that the Ang II type 1 receptor exerts a critical role in cardiovascular and kidney diseases independent of blood pressure elevation. In the last two decades, the identification of an increased number of peptides and receptors has facilitated the concept that the RAS has both detrimental and beneficial effects on the cardiovascular system depending on which RAS components are activated. For example, angiotensin 1-7 and Ang II type 2 receptors act as a counter-regulatory system against the classical RAS by mediating vasodilation. While the RAS as an endocrine system for regulation of blood pressure is well established, there remain many unanswered questions and controversial findings regarding blood pressure regulation and pathophysiological regulation of cardiovascular diseases at the tissue level. This review article will include the latest knowledge gleaned from cell type-selective gene deleted mice regarding cell type-specific roles of AngII receptors and discuss their significance in health and diseases. In particular, we focus on the roles of these receptors expressed in vascular, cardiac, and kidney epithelial cells.