Abstract
Na + /K + -ATPase is essential in maintenance of electrolyte, acid-base and volume homeostasis in kidneys. Increased renal Na/K pump activity has been reported to be associated with elevated blood pressure. Since blood pressure changes are paralleled by alterations in Na/K pump activity, it is proposed that impaired Na + /K + -ATPase signaling may contribute to imbalanced volume homeostasis and hypertension as well as increased salt sensitivity. Recently, we developed a novel technique called synchronization modulation electric field (SMEF) to electrically modulate the Na/K pump functions. The SMEF first synchronizes the pump molecules so that all the pumps simultaneously extrude Na + ions and pump in K + ions. Then, by accurately and precisely accelerating or decelerating the pumping rate, SMEF can consequently regulate renal tubular reabsorption and excretion capacity. In this study, we tested the effectiveness of SMEF in the controls of the tubular reabsorption and the regulation of blood pressure in health and hypertensive rat models. In normal SD rats (n=5), urinary flow rates were measured for the left and right kidneys of the same rat. When the SMEF was turned on only on the left kidney with backward modulation at the target frequency of 10 Hz to slow Na/K pumping rate, the urinary flow rate of the left kidney was quickly increased to 5.6±0.3 μl/min/g KW from the basal value of 4±0.4 μl/min/g KW. While the right kidney without SMEF application kept a constant basal urinary flow and Na+ excretion rate. In the Ang II induced hypertensive rat models (n=6), the MAP was gradually lowered by 8 mmHg than the control group when the backward modulation of SMEF was applied, accompanied by an increase of about 13 ml/day in water intake. We then applied the SMEF to the Dahl salt sensitive (SS) rats (n=5). The MAP in control group started to increase after 3-5 days of high salt intake. The SMEF was then applied from 7 days after switching to a high salt diet till the end of the experiments. The MAP quickly reduced by >30 mmHg (from 148 ± 7 to 117 ± 8 mmHg). These data demonstrated that backward modulation of SMEF lowered blood pressure possibly by promoting Na + and water excretion. SMEF could be an efficient treatment strategy for salt-sensitive hypertension.
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