CYCLOOXYGENASE-2 PARTICIPATES IN TUBULAR FLOW-DEPENDENT AFFERENT ARTERIOLAR TONE - INTERACTION WITH NEURONAL NOS

To delineate the microvascular role of cyclooxygenase-2 (Cox-2) in mod ulating tubuloglomerular feedback (TGF) signals and to determine its r elationship to neuronal nitric oxide synthase (nNOS), afferent (AA) an d efferent (EA) arteriolar diameters of rat kidneys were assessed usin g the blood-perfused juxtamedullary nephron technique. The Cox-2 inhib itor NS-398 (10 mu M) did not alter AA diameters in untreated kidneys but significantly constricted AAs by 17.0 +/- 2.2% in kidneys treated with 10 mM acetazolamide, which enhances TGF-mediated AA constriction by increasing distal volume delivery. The NS-398-induced AA constricti on was prevented after interruption of distal delivery by transection of the loops of Henle. The effect was selective for AAs since NS-398 d id not influence EAs of untreated or acetazolamide-treated kidneys. Pr etreatment with the nNOS inhibitor S-methyl-L-thiocitrulline (10 mu M) prevented the NS-398-induced AA constriction observed during acetazol amide treatment. Although we previously demonstrated that acetazolamid e treatment enhanced AA constrictor response to S-methyl-L-thiocitrull ine, the enhancement by acetazolamide was inhibited by pretreatment wi th 10 mu M: NS-398 (16.4 +/- 1.9 and 15.0 +/- 0.5% with and without ac etazolamide, respectively, P > 0.05). These results indicate that, dur ing increased activation of TGF-dependent vasoconstrictor signals, Cox -2 generates vasodilatory metabolites in response to increased nNOS ac tivity and thus participates in the counteracting modulation of TGF-me diated AA constriction.