A Memorial to Robert Tiegerstedt

One hundred years have passed since the first discovery of renin as a “pressor substance” in 1898 by Robert Tiegerstedt at Karolinska Institute. Since then, we have undergone long and difficult but highly productive years of renin-angiotensin research.This work was an important breakthrough in the context of the new concept of the endocrine mechanism “milieu interior” initiated by Claude Bernard. The 48-page publication “Niere und Kreislauf” in Skandinavisches Archiev fur Physiologie in 1898 by Tiegerstedt and Bergman detailed their meticulous approaches, even including the design of a flowmeter to measure blood pressure changes and documentation of long-lasting pressor effects of renin and tachyphylaxis.1 Curiously, however, no sequel study was published. According to Professor Mattias Aurell, this was because of the rather poor reproducibility of renin activity measurement, a well-known feature that has troubled many renin investigators since then. The choice of the kidney as the source of renin had an important implication because it coincided with the long-standing recognition that high blood pressure goes hand in hand with kidney diseases.The kidney became the target of studies again 30 some years later in independently conducted studies by Goldblatt, a pathologist who succeeded in making a dog model of renovascular hypertension by constricting the renal artery with silver clips. This work is based on Goldblatt’s repeated observations that renal arterial stenosis frequently accompanies hypertension. He also found that venous plasma of ipsilateral kidney contains a vasopressor substance.Study of renin-angiotensin was given a solid base when renin was found to be a peptidase that produces the pressor peptide angiotensin (a hybrid of angiotonin and hypertensin), demonstrated by Page and Braun-Menendez and their associates in the late 1930s. Angiotensin I (Ang I) was isolated by Skeggs et al, and the structure of Ang II was determined by Lentz et al, …