Role of cyclooxygenase-2-derived metabolites and NO in renal response to bradykinin

It has been reported that bradykinin (BK) can induce or activate both cyclo oxygenase (COX) isoforms and that the renal effects of BK seem to be mediat ed by prostaglandins and NO. The first objective of this study was to evalu ate the relative contribution of both COX isoforms in mediating the renal r esponse to BK in anesthetized dogs. The second objective was to examine whe ther COX-2 inhibition potentiates the renal effects induced by NO reduction during BK administration. Intrarenal BK infusion (8 ng . kg(-1) . min(-1), n=6) elicited a significant increment in renal blood flow, sodium excretio n, urine volume, and the fractional excretion of lithium. COX-2 inhibition (nimesulide, 5 mug . kg(-1) . min(-1), n=6) reduced the renal vasodilatatio n but did not significantly modify the natriuresis or diuresis secondary to BK. Administration of a nonspecific isozyme COX inhibitor (meclofenamate, 5 mug . kg(-1) . min(-1); n=6) did not induce greater effects than those pr oduced by nimesulide. NO synthesis reduction (N-G-nitro-L-arginine methyl e ster [L-NAME], 3 mug . kg(-1) . min(-1)) prevented the renal vasodilatation and the increment in the fractional excretion of lithium induced by BK but did not affect the natriuretic or diuretic response. Simultaneous nimesuli de infusion did not modify the renal effects of L-NAME during BK infusion ( n=6): Finally, inhibition of both COX isoforms with meclofenamate, in dogs treated with L-NAME (n=6), completely prevented the vasodilator and excreto ry actions of BK. The results of this study suggest that (1) NO and prostan oids dependent on COX-2 seem to be involved in the renal vasodilatation ind uced by BK, and (2) there is an interaction between NO and COX-1-derived me tabolites in mediating the natriuretic and diuretic response to BK.