LOCALIZATION OF BRADYKININ B-2 BINDING-SITES IN RAT-KIDNEY FOLLOWING CHRONIC ACE-INHIBITOR TREATMENT

Bradykinin exerts important influences on renal hemodynamics and tubul ar function by acting on renal bradykinin B-2 receptors. However, the precise sites and mechanisms of its actions on the kidney are not know n. To help elucidate the mechanisms of renal actions of bradykinin in vivo, we have employed high resolution electron microscopic autoradiog raphy to localize bradykinin B-2 binding sites in the rat kidney follo wing intravenous administration of a radiolabelled ligand, I-125-HPP-H oe140 (3-4-Hydroxyphenyl-propionyl-DArg(0)-[Hyp(3)- Tic(7)-Oic(8)]-bra dykinin), a derivative of the highly selective bradykinin B-2 receptor antagonist, Hoe140. In non-treated rats, bradykinin B-2 binding sites were localized to the cell bodies and the luminal brush border of the proximal convoluted tubules in the cortex. In the medulla (except for the outer stripe of the outer medulla), binding occurred in the dista l tubules, thin limbs of the loop of Henle, collecting ducts, peritubu lar capillary endothelium and renomedullary interstitial cells. To exc lude the possibility that the radioligand may bind to angiotensin conv erting enzyme, rats were pretreated with the angiotensin converting en zyme inhibitor, perindopril. In these rats, binding to the cell bodies and the luminal brush border of the proximal convoluted tubules in th e cortex was completely abolished, while binding remained unaltered in the medulla. Further studies using high performance liquid chromatogr aphy revealed that while the radioligand was degraded following system ic administration in nontreated rats, the degradation was significantl y reduced in the rats pretreated chronically with perindopril. These r esults indicate that binding detected in the proximal tubules in the n ormal rats is due primarily to the tubular uptake of the degraded radi oligand, and that bradykinin B-2 binding sites occur predominantly in the renal tubules, vascular endothelium, and renomedullary interstitia l cells of the renal medulla.