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-angiotensinaldosterone 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 relations based on feedback 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). The observations from 1934 were of similar significance: the correlation between dog kidney ischaemia and the occurrence of hypertension was found. 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. In 1939, it was proved that under the influence of renin blood pressure-rising peptides are formed. Consequently, it was documented that angiotensin was the cause of hypertension in animals with ischaemic kidney, and in 1954 the sequence of angiotensin I and II was described. In 1960–1961 systemic RAA occurrences were identified. 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 is the research of Hirofumi Sokabe and Hiroko Nishimura, which, among others, is the basis for this manuscript.