Biochemistry and pharmacology of the renin-angiotensin system.

Abstract

Knowledge of the structure, function and distribution of the components of the renin-angiotensin-aldosterone system (RAS) and the integrated physiological role of this hormonal system is rapidly increasing, although many questions remain unanswered. The primary structure and localisation of RAS such as renin, prorenin, angiotensinogen, angiotensin-converting enzyme (ACE) and the angiotensins have now been described. Moreover, the genes for the production of renin and ACE have been cloned and their nucleotide sequences determined. In addition to its well-established role as a circulating endocrine system, the renin-angiotensin system has more recently been ascribed a local autocrine or paracrine function. Physiologically active levels of components such as renin and angiotensin, or their messenger RNAs, have been identified in several extrarenal tissues, notably the central nervous system. The components of such tissue renin-angiotensin systems may be derived from de novo tissue synthesis and/or from the circulation by endocytosis. Angiotensin has pharmacological actions on a wide range of body tissues, including the kidney, heart, brain, gastrointestinal tract and reproductive organs. In many of these locations, angiotensin receptors have been isolated and characterised. The most firmly established roles of angiotensin are the control of blood pressure and local blood flow, and in salt and water homeostasis; the physiological significance of many of angiotensin's tissue effects is unknown. In some areas of clinical interest, such as the pathophysiology of left ventricular hypertrophy, ACE inhibitors are very useful for elucidating the possible influences of the renin-angiotensin system.