Dynamic interactions between integrative physiology and molecular medicine: the key to understand the mechanism of action of aldosterone in the kidney.

Our objective is to illustrate how an approach that integrates new insights from molecular biology and traditional physiology can lead to the development of new concepts. This dynamic interaction is illustrated by examining the steps taken to improve our understanding of the renal actions of aldosterone. We began by defining the big picture of what aldosterone does in the kidney. This led to the conclusion that aldosterone must at times become a sodium chloride-retaining hormone, while at other times it must function primarily or exclusively as a kaliuretic hormone. The second step was to define the major molecular actions of this hormone. Acting on the principal cells in the cortical collecting duct (CCD), aldosterone leads to the insertion of active epithelial sodium ion channels (ENaC) in their luminal membranes. This active ENaC, however, does not distinguish between the two major renal actions of aldosterone. Accordingly, we returned to integrative physiology and examined a possible role of renal and non-renal events. We implicated the potential importance of the delivery of bicarbonate ions to the CCD to determine which effect of aldosterone will become manifest. This, however, required that we reconsider some of the traditional views in interpretation of acid-base balance. At the clinical level, this global view can help us understand why, for example, a low dietary intake of potassium salts might predispose a person to an elevated blood pressure. Using a similar approach, it is possible to understand how the risk of the formation of kidney stones can be minimized.