Interactions of Lysyl-Bradykinin

Although intrarenal infusions of kinins produce diuresis, it is not clear to what extent this response is due to hemodynamically mediated medullary washout and/or to direct epithelial effects ofkinins. Recent evidence has shown that bradykinin binds to collecting tubules in vitro. We therefore examined the interactions of lysyl-bradykinin and antidiuretic hormone (ADH) with respect to hydraulic conductivity (L,) in the rabbit cortical collecting tubule perfused in vitro. To ensure adequate substrate for prostaglandin synthesis, the bath contained 2.5 qM arachidonic acid. Arachidonic acid produced no change in base-line lp and had no effect on the subsequent response to a supramaximal dose ofADH (100 ,U/ml). Therefore, all subsequent experiments were done in the presence of arachidonic acid. Lysyl-bradykinin (10-9 M) added to either the lumen or bath had no effect on baseline Lp. Collecting tubules which were exposed for 1 h to bath lysyl-bradykinin (10-9 M) had a significantly diminished subsequent Lp in response to ADH (P < 0.02). In tubules exposed to bath lysyl-bradykinin plus indomethacin (5 pM), the subsequent ADH response was normal. Lysyl-bradykinin (10-9 M) added to the lumen had no effect on subsequent ADH response. We conclude that lysyl-bradykinin from the basolateral side inhibits the hydroosmotic response ofthe cortical collecting tubule to ADH, and that this inhibition is probably prostaglandin-mediated. Lysyl-bradykinin does not affect water flow from the luminal surface. These Dr. Schuster was a Roche Fellow of the National Kidney Foundation during part of this work. Please address correspondence to Dr. Jacobson, Department of Internal Medicine, University of Texas Science Center, Dallas, TX 75235. Received for publication 29 September 1983 and in revised form 1 March 1984. data indicate that the diuresis seen with kinin infusions may result, at least in part, from a direct epithelial effect. They also suggest a role ofthe renal kallikrein-kinin system in modulating water transport in vivo.