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 developm ent of new concepts. This dynamic interaction is illustrated by examining t he steps taken to improve our understanding of the renal actions of aldoste rone. 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 pr imarily or exclusively as a kaliuretic hormone. The second step was to defi ne the major molecular actions of this hormone. Acting on the principal cel ls in the cortical collecting duct (CCD), aldosterone leads to the insertio n of active epithelial sodium ion channels (ENaC) in their luminal membrane s. This active ENaC, however, does not distinguish between the two major re nal actions of aldosterone. Accordingly, we returned to integrative physiol ogy and examined a possible role of renal and non-renal events. We implicat ed the potential importance of the delivery of bicarbonate ions to the CCD to determine which effect of aldosterone will become manifest. This, howeve r, required that we reconsider some of the traditional views in interpretat ion 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 mig ht predispose a person to an elevated blood pressure. Using a similar appro ach, it is possible to understand how the risk of the formation of kidney s tones can be minimized.