Sodium Handling and Interaction in Numerous Organs

Abstract

Salt (NaCl) is a prerequisite for life. Excessive intake of salt, however, is said to increase disease risk, including hypertension, arteriosclerosis, heart failure, renal disease, stroke, and cancer. Therefore, considerable research has been expended on the mechanism of sodium handling based on the current concepts of sodium balance. The studies have necessarily relied on relatively short-term experiments and focused on extremes of salt intake in humans. Ultra-long-term salt balance has received far less attention. We performed long-term salt balance studies at intakes of 6, 9, and 12 g/day and found that although the kidney remains the long-term excretory gate, tissue and plasma sodium concentrations are not necessarily the same and that urinary salt excretion does not necessarily reflect total-body salt content. We found that to excrete salt, the body makes a great effort to conserve water, resulting in a natriuretic-ureotelic principle of salt excretion. Of note, renal sodium handling is characterized by osmolyte excretion with anti-parallel water reabsorption, a state-of-affairs that is achieved through the interaction of multiple organs. In this review, we discuss novel sodium and water balance concepts in reference to our ultra-long-term study. An important key to understanding body sodium metabolism is to focus on water conservation, a biological principle to protect from dehydration, since excess dietary salt excretion into the urine predisposes to renal water loss because of natriuresis. We believe that our research direction is relevant not only to salt balance but also to cardiovascular regulatory mechanisms.

Keywords: blood pressure; body fluid; energy metabolism; estivation; hypertension; osmolyte; salt; urea.

Figure 1.

Recent accumulating evidence advocates that body sodium handling is achieved by an adjustment of the interaction of multiple organs. Tissue sodium content is not always constant even under the controlled salt intake whereas blood sodium concentration is a steady level. The immune cells-regulated lymphatic sodium clearance system enables the localized skin to regulate sodium storage and release independently of plasma sodium concentration. Alteration in dietary salt intake is characterized by renal natriuretic-ureotelic regulation, hepatic urea production, and changes in energy metabolism in the liver, the muscle, and the heart. A possible regulatory candidate for the sodium and water balance is endogenous hormonal rhythm including steroid hormones.