title: Role of Cyclooxygenase-2-Derived Metabolites and NO in Renal Response to Bradykinin.
abstract: -It has been reported that bradykinin (BK) can induce or activate both cyclooxygenase (COX) isoforms and that the renal effects of BK seem to be mediated by prostaglandins and NO. The first objective of this study was to evaluate the relative contribution of both COX isoforms in mediating the renal response to BK in anesthetized dogs. The second objective was to examine whether 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 excretion, urine volume, and the fractional excretion of lithium. COX-2 inhibition (nimesulide, 5 µg. kg(-1). min(-1), n=6) reduced the renal vasodilatation but did not significantly modify the natriuresis or diuresis secondary to BK. Administration of a nonspecific isozyme COX inhibitor (meclofenamate, 5 µg. kg(-1). min(-1); n=6) did not induce greater effects than those produced by nimesulide. NO synthesis reduction (N:(G)-nitro-L-arginine methyl ester [L-NAME], 3 µg. 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 nimesulide 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 excretory actions of BK. The results of this study suggest that (1) NO and prostanoids dependent on COX-2 seem to be involved in the renal vasodilatation induced by BK, and (2) there is an interaction between NO and COX-1-derived metabolites in mediating the natriuretic and diuretic response to BK.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Murcia, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Rodríguez
authors.forename: María T.
authors.initials: MT
authors.lastname: Llinás
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.forename: F. Javier
authors.initials: FJ
authors.lastname: Salazar