PERMEABILITY CRITERIA FOR EFFECTIVE FUNCTION OF PASSIVE COUNTERCURRENT MULTIPLIER

The urine concentrating effect of the mammalian renal inner medulla ha s been attributed to countercurrent multiplication of a transepithelia l osmotic difference arising from passive absorption of NaCl from thin ascending limbs of long loops of Henle. This study assesses, both mat hematically and experimentally, whether the permeability criteria for effective function of this passive hypothesis are consistent with tran sport properties measured in long loops of Henle of chinchilla. Mathem atical simulations incorporating loop of Henle transepithelial permeab ilities idealized for the passive hypothesis generated a steep inner m edullary osmotic gradient, confirming the fundamental feasibility of t he passive hypothesis. However, when permeabilities measured in chinch illa were used, no inner medullary gradient was generated. A key param eter in the apparent failure of the passive hypothesis is the long-loo p descending limb (LDL) urea permeability, which must be small to prev ent significant transepithelial urea flux into inner medullary LDL. Co nsequently, experiments in isolated perfused thin LDL were conducted t o determine whether the urea permeability may be lower under condition s more nearly resembling those in the inner medulla. LDL segments were dissected from 30-70% of the distance along the inner medullary axis of the chinchilla kidney. The factors tested were NaCl concentration ( 125-400 mM in perfusate and bath), urea concentration (5-500 mM in per fusate and bath), calcium concentration (2-8 mM in perfusate and bath) , and protamine concentration (300 mu g/ml in perfusate). None of thes e factors significantly altered the measured urea permeability, which exceeded 20 x 10(-5) cm/s for all conditions. Simulation results show that this moderately high urea permeability in LDL is an order of magn itude too high for effective operation of the passive countercurrent m ultiplier.