Clinical Drug Experience Knowledgebase

Diets containing excessive salt (>12 g/day) have negative effects on kidney and cardiovascular system. Considering this known fact, the investigators aimed to study if the amount of the water taken with excessive salt had any part on these negative effects by testing the blood pressure, serum osmolality, endothelial functions, cardiac function, inflammatory parameters and sympathetic nervous system.

Excessive dietary salt raises the serum osmolality, which triggers the protection mechanisms of the body. The first mechanism is the secretion of vasopressin from posterior pituitary and the second one is the polyol mediated aldose reductase enzyme activation in renal tubules. In the beginning, water and a little amount of salt is reabsorbed from the kidneys for keeping the serum osmolality in normal ranges by the elevation of vasopressin. Besides the high levels of vasopressin for long durations may have a role in both developments of hypertension and the progression/development of chronic kidney disease. Polyol mediated aldose reductase enzyme turns glucose into sorbitol, which is turned to fructose by sorbitol dehydrogenase activity. Fructose is degraded by fructokinase activity into toxic substances. With this pathway, the acute energy need is satisfied, yet uric acid, local oxidative stress, and inflammatory mediators rise while nitric oxide levels decreasing. These facts are independent risk factors for both kidney disease progression and hypertension. In addition, excessive salt intake may elevate the transforming growth factor beta-1 (TGF-B1) levels, which activates the sympathetic system, inflammation, and endothelial dysfunction.

According to these data, the investigators speculate that if they increase the amount of water intake while eating the high salt diet they may decrease the toxic effect of salt with less increase in serum osmolarity. To test this hypothesis, by regulating the salt and water amount in healthy people's diets, the investigators aimed to evaluate the following these parameters; biochemical parameters that could affect the blood and urine osmolality, blood pressure, vascular endothelial functions with the non-invasive flow-mediated dilatation technique and arterial stiffness, systolic and diastolic functions of the heart by transthoracic echocardiography. In addition, it was planned to evaluate the hormonal effects of arginine vasopressin, a long peptide with 39 amino acids, which is longer and easier to measure than vasopressin levels in serum by measuring the pituitary hormone-derived copeptin.

Although, decreasing the salt intake is the first step of the treatment in hypertension, and kidney diseases, the compliance rate to less sodium intake is very low (<20%). The investigators aim is to evaluate the effects of water, which is taken acutely with the excessive salt intake on cardiovascular system and kidney. The findings of the study will important for public health. If the investigators prove their hypothesis, they may recommend increasing high water intake before feeling thirst of which may contribute to decreasing the prevalence of hypertension and kidney disease.