The renin-angiotensin system and the heart: a historical review

Early observations on a possible link between the kidney and the cardiovascular system In 1836 an English clinician Richard Bright observed that patients dying with contracted kidneys often had a hard, full pulse and cardiac hypertrophy.'In 1889 Brown-Sequard, the "father" of endocrinology, showed that injec- tions of extracts from guinea pig testicles were able to produce systemic effects of vigour and the perception of rejuvenation.2On this back- ground, in 1896 the Finnish physiologist Robert Tigerstedt and his student Per Bergman began to explore the possibility that kidney extracts from rabbits may have some systemic effects on the cardiovascular system.In 1898 their classic paper was published showing that intravenous injection of these renal extracts exerted a pressor effect.Moreover they postulated that the substance responsible for this effect was a protein which they named renin.They further suggested that renin was released from the kidney into the blood to produce an effect on blood vessels at a distance: another of the earliest ideas on blood borne chemical messengers.34Eight years later Tigerstedt described a pressor effect of renal venous blood although he admitted that the evidence for this was weak.5Other groups could not reproduce Tigerstedt's results, prob- ably because they failed to prevent proteolysis in the preparation of the renal extracts.Therefore enthusiasm for the concept of renin as a pressor substance waned.Tigerstedt died in 1923 without any real acknowledgment of the significance of his contribution to the fields of both endocrinology and cardiovascular homeostasis.In fact for 30 years there were few references to the pressor effects of renin in the literature.In 1925, the histologist Ruyter was the first to describe granulated cells in the walls of the glomerular arterioles.6The significance of this was realised by Goormaghtigh in 19397 after the concept of renin as a hormone had been rekindled.