From Angiotensin to Renin to Prorenin and from the Adrenal to the Kidney to the Placenta and the Lungs: An Historical Journey

In 1966 I carried out a study on the role of calcium on angiotensin’s stimulant effects on the adrenal medulla. Since then I have been studying the renin-angiotensin system (RAS) for over a half-century in a wide variety of biological preparations, while awareness of its complexity has exploded. My journey has involved studies on genes, proteins, organelles, cells, tissues, glands, organs and whole animals. This chapter reviews what my colleagues and I have learned from these different levels of organization and is not meant to be an update on all features of the RAS. My studies have included experiments on: perfused cat adrenal glands; genetic and second messenger control of catecholamine synthesis and secretion from cultured bovine chromaffin cells and from rats in vivo; renin storage and release in the rat kidney and secretory granules; properties of isolated renin, prorenin and renin-like proteins; hormonal and second messenger control of prorenin secretion from human utero-placental tissues; renin/prorenin in a variety of tumors; and the effect of RAS drugs in a rodent model of pulmonary fat embolism. This most recent study has direct clinical application. I conclude with what I have learned about biomedical research and lessons for the future.