Effects of dietary potassium depletion in salt-dependent hypertension, the kidney, electrolyte balance, and sympathetic nervous system in Dahl rats

grantor: University of TorontoStudies described in this thesis were designed to test my general hypothesis, i.e. Reduction of dietary potassium exacerbates salt-dependent hypertension by promoting urinary excretion of divalent cations, by altering vascular morphology, and/or by stimulating the sympathetic nervous system. To test the hypothesis, weanling Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats which were fed with a high salt diet (8% NaCl) containing either high (4%-HSHK) or low (0.2%-HSLK) potassium for one month. Results demonstrated that prolonged potassium restriction on a high salt diet exacerbated hypertension in the S rats. It also raised blood pressure in the R rats. The hypertension was not related to water and sodium retention, rather, it was correlated with excess excretion of calcium and magnesium in the kidney. The hypertension was also associated with renal vascular remodeling which were characterized by reduced lumen diameter, enlarged wall thickness to lumen ratio with or without changing cross-sectional wall area of renal vessels. To differentiate renal functional changes from a renal perfusion pressure effect, vasoconstrictors (angiotensin II, arginine vasopressin, phenylephrine) were used to raise systemic blood pressure acutely in Sprague-Dawley rats fed on normal rat chow. A customized cuff was placed around the aorta of anesthetized animal between two renal arteries to prevent rise of renal perfusion pressure in only one of the two kidneys. Results demonstrated that hypercalciuria and hypermagnesiuria occurred only in the kidney in which renal perfusion pressure was allowed to rise, therefore, they were renal perfusion pressure-dependent. In the chronic state, chemical sympathectomy with 6-hydroxydopamine was used to prevent systemic blood pressure from increasing in both S and R rats during a two month HSLK feeding. Results demonstrated that chemical sympathectomy abolished hypertension in R rats. It delayed and reduced hypertension development in S rats. In addition, S rats had reduced intestinal absorption, and increased urinary excretion of calcium and magnesium. It is concluded that in R rats, an activated sympathetic nervous system fully explains the rise of pressure, possibly operating via direct vascular influences. In S rats, an additional mechanism is an inherent defect in intestinal and renal (re)absorption of divalent cations, leading to exacerbation of hypertension.Ph.D