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The aim of the present study was to determine whether bradykinin affects NaCl reabsorption in the medullary thick ascending limb of the loop of Henle. At 10(-8) M, bradykinin significantly inhibited Cl- transport in the in vitro microperfused rat medullary thick ascending limb by 67% (P0.01). This inhibitory effect could be totally prevented by preincubating tubules with the bradykinin B2 receptor antagonist N alpha-adamantaneacetyl-D-Arg-[Hyp3,Thi5,8,D-Phe7]brady kinin (10(-6) M). In contrast, the bradykinin B1 receptor agonist des-Arg9 bradykinin (10(-6) M) had no effect on Cl- transport. Bradykinin caused transient increases in intracellular Ca2+ concentration, which could be blocked by the bradykinin B2 receptor antagonist, but could not be reproduced with the bradykinin B1 receptor agonist. These data suggest that the natriuretic and diuretic effect of bradykinin in vivo is due, at least in part, to a bradykinin B2 receptor-mediated inhibition of NaCl reabsorption in the medullary thick ascending limb of the loop of Henle. |
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