URODILATIN - A NATRIURETIC PEPTIDE OF RENAL ORIGIN

More than three decades ago, H. W. Smith and H. E. DeWardener reported, in separate studies, that the natriuresis observed after volume expansion or sodium loading could not be attributed solely to increases in the glomerular filtration rate or changes in plasma levels of aldosterone (69,82). In addition, DeWardener showed, in a classic experiment, that infusion of blood from "volume-expanded" dogs into normal dogs induced an increase in the excretion of sodium by the recipients (82,83). These findings provided strong evidence for the existence of a circulating natriuretic substance, regulated by the central blood volume. At about the same time, Kisch reported the presence of secretory granules in guinea pig atrial cardiocytes (41). In 1976, Marie et al. demonstrated that a high salt intake, with or without desoxycorticosterone (DOCA), decreased the concentration of these granules, whereas sodium and water depletion increased their number (48). In 1979, deBold confirmed these findings, suggesting that the atrial granularity was related to changes in fluid balance in the body and that the content of these secretory granules could affect renal function (11). Two years later, deBold et al. (12) reported that injection of an extract of rat atria produced increases of approximately 30-fold and 10-fold in sodium excretion and urine flow, respectively. Injections of extracts of ventricular tissue did not exert a significant effect on these parameters (12). This work was the first to provide proof that the atria contain a natriuretic substance, which is presumably released into the circulation in response to volume expansion or other stimuli that increase atrial stretch. The substance was referred to as atrial natriuretic factor (ANF) (12), atrial natriuretic peptide (ANP), cardiodilatin (13), atriopeptin (16), or auriculin (7). Within a few years, the biochemistry, molecular biology and physiology of ANF were described.