The renin and angiotensin system part 1

Biochemical aspects of renin

Abstract

In an attempt to find the link between excessive sodium intake and high blood pressure, we established the identity of renin and the presence of tissue renin. We isolated renin in a pure and stable form for the first time, and established a novel concept that a specific hormone producing peptidase exists that is not a digestive protease. We determined the complete amino acid sequence, and identified a catalytically essential pair of aspartyl residues by two specific inhibitors. These studies showed that renin is an aspartyl protease with a highly stringent substrate specificity limited to the cleavage of one specific leucyl-leucyl (or leucyl-valyl in humans) peptide bond in angiotensinogen. We showed that renin is not isorenin, pseudo-renin or a renin-like enzyme but is a unique enzyme. By preparing specific antibodies to pure renin, and affinity separation from cathepsin, we found the presence of non-secreted renin in the brain, pituitary, adrenal, testis and other tissues in which it produces angiotensins by an intracellular mechanism that later was extended to the heart, vasculature and kidney. The presence of tissue bound renin was also suggested. These results can explain local effects of angiotensin II, particularly when plasma renin concentration and its pathophysiological effects are not proportional.