Effect of antidiuretic hormone on lithium as a marker for proximal tubule delivery

To determine whether acute changes in antidiuretic hormone (ADH) alter the ability of lithium to quantitatively reflect proximal delivery, fractional lithium excretion (CLi/CIn) and late proximal (TF/P)In determined by micropuncture were measured in sodium-loaded rats following administration of desamino-8-D-arginine vasopressin (dDAVP) at rates equivalent to approximately half-maximal (20 pg/min) and maximal (40 pg/min) plasma levels of endogenous hormone. dDAVP dissociated the linear correlation between CLi/CIn and 1/(TF/P)In (r = 0.05) usually observed in sodium-loaded rats. Proximal delivery determined by lithium clearance underestimated (P less than 0.001) values obtained by micropuncture. Amiloride restored the linear correlation between CLi/CIn and 1/(TF/P)In in sodium-loaded dDAVP-treated rats (r = 0.70) and quantitative estimates of proximal delivery by each technique became equivalent. Indomethacin also reduced (P less than 0.001) estimates of proximal delivery obtained by lithium techniques in sodium-loaded rats. Water loading in hydropenic rats restored concordance between estimates of proximal delivery obtained by lithium clearance and micropuncture methods. Thus changes in ADH markedly alter the ability of lithium to function as a quantitative marker for proximal delivery. Furthermore, ADH may increase lithium uptake at distal nephron sites by an amiloride-sensitive pathway.