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

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Abstract
ATP-sensitive potassium channels (KATP) 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 KATP 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 KATP 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 (Jv), Na+(JNa), Cl−(JCl), and K+(JK) absorption.Jv increased 44% (from 8.32 to 11.95 nl/min), JNa increased 14% (from 1.96 to 2.34 nmol/min), JCl increased 21% (from 1.72 to 2.08 nmol/min), and JK increased 57% (from 35.8 to 56.4 pmol/min). We conclude that the activation of KATP 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.