Integrative Physiology |
From the Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada.
Correspondence to Rodger D. Loutzenhiser, PhD, Department of Pharmacology and Therapeutics, University of Calgary, Health Sciences Centre, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. E-mail rloutzen{at}ucalgary.ca
AbstractAn inward rectifier potassium current, Kir, has been identified in cerebral and coronary resistance vessels, where it is considered to be an important determinant of resting membrane potential (RMP) and to play a role in blood flow regulation. We investigated the functional role of Kir in the renal afferent arteriole using the in vitroperfused hydronephrotic rat kidney. Increasing external KCl from 5 to 15 mmol/L induced afferent arteriolar vasodilation. This response was inhibited by 10 to 100 µmol/L Ba2+, concentrations selective for blockade of Kir, and by chloroethylclonidine (100 µmol/L) but was not blocked by glibenclamide (10 µmol/L) or ouabain (3 mmol/L). Reducing external KCl from 5 to 1.5 mmol/L to enhance rectification of Kir caused vasoconstriction at low renal arterial pressure (40 mm Hg) and vasodilation during myogenic vasoconstriction (120 mm Hg), suggesting that this current dominates RMP at low perfusion pressures. When administered to kidneys perfused at 40 mm Hg renal arterial pressure, 30 µmol/L Ba2+ elicited afferent arteriolar depolarization, reducing RMP from -47±2 to -34±2 mV (n=10, P<0.0001), and vasoconstriction, reducing diameters from 14.5±1 to 10.9±0.8 µm (n=10, P=0.0016). Although Ba2+ reduced resting diameter, blockade of Kir did not prevent myogenic signaling in this vessel. Our findings thus demonstrate the presence of Kir in rat renal afferent arterioles and suggest that this current is an important determinant of RMP in situ.
Key Words: renal hemodynamics renal microcirculation membrane potential barium ouabain
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