Structure and Regulation of Prorenin

The treatment and prevention of cardiovascular disease is one ofthe triumphs of modern medicine but we have a long way to go before this success is completed. Heart attack and stroke are still common and, in the western world, cardiovascular disease remains the main cause of morbidity and mortality. A major player in cardiovascular homeostasis is the renin.angiotensin system (RAS), and the growing knowledge of this system has led to the development of agents that specifically interact with components that are part of the RAS. 'Anti-RAS' drugs are now widely used in the management of hypertension, heart failure and diabetic nephropathy. However, as is true for cardiovascular medicine in general, many problems remain to be solved. Our understanding of how the RAS works and how to modify its actions is still far from complete. One century ago Tigerstedt and Bergmann coined the name 'renin' for a hypertensive factor in rabbit kidney. I They showed that this factor was present in renal cortex and that it was secreted into renal venous blood. It was retained by dialysis membranes and sensitive to heat, which suggested its protein. nature. After these initial observations renin sank into oblivion for a few decades until interest flared up after the experiments by Goldblatt et al., who showed that clamping a renal artery in a dog caused hypertension. They believed a humoral factor to be the hypertensive principle, which was shown to be renin by Pickering et al. From then on unraveling of the structure of what nowadays is known as the RAS made steady progress, culminating in the cloning of the genes of its constituents.

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