AT(1) receptors and control of blood pressure: the kidney and more

The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. The components of the RAS including renin, angiotensin-converting enzyme, and angiotensin receptors are expressed throughout the body in tissues that may impact blood pressure control. Blocking actions of individual components of the RAS including renin, angiotensin-converting enzyme, or the type 1 (AT(1)) receptor lowers blood pressure. Although it has been suggested that control of sodium excretion by the kidney is the dominant mechanism for blood pressure regulation by the RAS, pharmacologic antagonists or conventional gene-targeting experiments globally interrupt the RAS and cannot discriminate its actions in the kidney from other tissue compartments. Recent experiments with the use of kidney cross-transplantation and genetically engineered mice suggest independent and equivalent effects of angiotensin II acting via AT(1) receptors in the kidney and in extrarenal tissues to maintain the normal level of blood pressure. However, the nature and relative contributions of these actions may differ in hypertension.