The evolutionary development of the renin angiotensin aldosterone system and its importance for the survival of the human species

Abstract

Kidneys produce a number of substances that affect intrarenal blood circulation; however, the key system that regulates blood flow in both general and local circulation (including the renal circulation) is the renin angiotensin-aldosterone system (RAAS). Individual elements of the RAA system are synthesized in separate tissues of the body under the influence of specific local factors. The system functions as a whole due to mutual compounds based on feedbacks and it consists of three basic elements: renin, angiotensin and aldosterone. The history of research on the RAA system dates back to the late 19th century. One of the important stages of exploring the mechanisms related to RAA system functioning was the publication (in 1898) of the results of research on the hypertensive effect on blood pressure of rabbit kidney extracts (containing renin)4 obtained by prof. Robert Tigerstedt and his assistant Per Bergman. Goldblatt observations from 1934 were of similar significance. He found a correlation between dog kidney ischaemia and the occurrence of hypertension. In the following years, the enzymatic properties and structure of renin and angiotensin peptides, resulting from the action of renin and the enzyme converting angiotensin I (Ang I) to its active form - angiotensin II (Ang II), were clarified. The latter belongs to the most important regulators of aldosterone secretion (discovered by Simpson, Tait and Wetstein in 1953). In 1939, Braun-Menandez and Page proved that under the influence of renin, peptide pressure compounds are formed. Consequently, it was documented that angiotensin was the cause of hypertension in animals with ischemic kidney, and in 1954 Skeggs described the sequence of angiotensin I and II. In 1960-1961, Davis, Genest, Laragh and others identified systemic RAA occurrences. However, to provide the insight of evolutionary significance of the RAA system for humans, the phylogenetic development of this enzyme-endocrine system in vertebrates should be investigated. The largest database of information regarding this system in the aforementioned group of animals are the research of Hirofumi Sokabe and Hiroko Nishimur, which, among others, are the basis for this manuscript.