THE ROLE OF B1-KININ AND B2-KININ RECEPTORS IN THE RENAL TUBULAR AND HEMODYNAMIC-RESPONSE TO BRADYKININ

Bradykinin (BK) is known to induce diuresis (UV), natriuresis (UNaV), and increase renal blood flow (RPF) with little or no change in glomerular filtration rate (GFR). In this study, BK is infused alone and concurrently with B1- or B2-kinin receptor antagonists into the left kidney of pentobarbital-anesthetized dogs. The intrarenal infusion of BK (bolus: 0.5-mu-g/kg, followed by a sustaining dose: 0.05-mu-g.kg-1.min-1) affected left kidney function only. In the left kidney, UV increased from 0.42 +/- 0.21 to a maximum of 1.88 +/- 0.55 ml/min (P < 0.01) and UNaV rose from 55 +/- 13 to 160 +/- 17-mu-eq/min (P < 0.01), while RPF was enhanced from 86 +/- 11 to 125 +/- 24 ml/min (P < 0.05), and GFR remained unchanged. When a B1-receptor antagonist ([Leu8]-des-Arg9-BK; 2.0-mu-g.kg-1. min-1) was infused concurrently with BK, the increase in urine flow was not different from BK alone. UNaV was transiently attenuated by 50% in this group (P < 0.05). A B2-receptor antagonist (D-Arg0,[Hyp3,D-Phe7]-BK; 2.0-mu-g.kg-1.min-1) infused with BK significantly (P < 0.05) and selectively inhibited by 50% the maximal diuresis provoked by BK alone. UNaV in this group was not different from that induced by BK alone. Finally, the concurrent infusion of either B1- or B2-antagonist completely inhibited the rise in RPF observed when BK was infused alone. We conclude that BK infused into the renal artery of dogs in vivo can alter UV and UNaV independently of global renal hemodynamic (RPF and GFR) changes. Furthermore, these data suggest that the activity of both B1- and B2-receptors is necessary for a BK-induced increase in global RPF.