The effects of the potassium channel opener minoxidil on renal electrolytes transport in the loop of henle.
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(+), Ca(2+), and Mg(2+). Intravenous injection of minoxidil (1.5 mg/kg) significantly decreased fractional Na(+) (FENa) and Mg(2+) (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 Ca(2+) 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.
Wang
Tong
T
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. tong.wang@yale.edu
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004573:Electrolytes / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004573:Electrolytes; D015221:Potassium Channels; D008914:Minoxidil