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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Effects of the Potassium Channel Opener Minoxidil on Renal Electrolytes Transport in the Loop of Henle

Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut

ATP-sensitive potassium channels (K_ATP) in the thick ascending limb of the loop of Henle play an important role in apical K⁺ recycling, a mechanism essential for maintaining the activity of the Na/2Cl/K-cotransporter. We have previously demonstrated that inhibition of K_ATP decreases Na⁺ and K⁺ absorption in the loop of Henle and induces diuretic and natriuretic effects. In the present study, we used renal clearance and in vivo microperfusion techniques to evaluate the effects of the K_ATP opener minoxidil on the urinary excretion and absorption in the loop of Henle of Na⁺, K⁺, Ca²⁺, and Mg²⁺. Intravenous injection of minoxidil (1.5 mg/kg) significantly decreased fractional Na⁺ (FENa) and Mg²⁺ (FEMg) excretion and urine volume with a moderate decrease in blood pressure (12%) and glomerular filtration rate (15%). Urine volume decreased 63%, and FENa and FEMg decreased 58 and 37%, respectively. In contrast, K⁺ and Ca²⁺ excretion did not change significantly. In the microperfusion of the loop of Henle, addition of minoxidil to the perfusion fluid significantly increased fluid (J_v), Na⁺ (J_Na), Cl^– (J_Cl), and K⁺ (J_K) absorption. J_v increased 44% (from 8.32 to 11.95 nl/min), J_Na increased 14% (from 1.96 to 2.34 nmol/min), J_Cl increased 21% (from 1.72 to 2.08 nmol/min), and J_K increased 57% (from 35.8 to 56.4 pmol/min). We conclude that the activation of K_ATP leads to stimulation of Na/2Cl/K-cotransporter activity and increases the rates of Na⁺, Cl^–, and K⁺ absorption in the loop of Henle, an effect contributing to the antidiuretic and antinatriuretic action of this K channel opener.

Address correspondence to: Dr. Tong Wang, Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. E-mail: tong.wang{at}yale.edu

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