Tissue renin-angiotensin system: sites of angiotensin formation

The classical concept of the renin-angiotensin system as an endocrine system, whereby angiotensin is generated in the circulation and conveyed by blood to peripheral tissues, is being increasingly challenged by evidence that suggests that peripheral tissues are the major site of generation of angiotensin I and II. The concentrations of angiotensins I and II in arterial and venous blood, taken together with their efficient metabolic clearance by peripheral tissues and their slow rate of generation in blood, indicate that peripheral tissues are the major site of generation of these peptides. Most angiotensin I and II in blood is generated within tissues by the action of plasma-derived renin on plasma-derived angiotensinogen, and the action of tissue converting enzyme. In addition, there is increasing evidence for the synthesis of renin by tissues other than the kidney, and of angiotensinogen by tissues other than the liver. The relative contribution of plasma renin and angiotensinogen, and of locally synthesized renin (or renin-like enzyme) and angiotensinogen, to angiotensin generation in each tissue is unknown, and probably differs between tissues. These two mechanisms for local generation of angiotensin within tissues have the potential to produce changes in tissue concentrations of angiotensin that are independent of the circulating level of renin and angiotensin.