Faculty Collaboration Database

Cyclooxygenase-2 participates in tubular flow-dependent afferent arteriolar tone: interaction with neuronal NOS. Am J Physiol 1998 Oct;275(4):F605-12

Date

10/01/1998

Pubmed ID

9755132

DOI

10.1152/ajprenal.1998.275.4.F605

Scopus ID

2-s2.0-0031755248 (requires institutional sign-in at Scopus site)   93 Citations

Abstract

To delineate the microvascular role of cyclooxygenase-2 (Cox-2) in modulating tubuloglomerular feedback (TGF) signals and to determine its relationship to neuronal nitric oxide synthase (nNOS), afferent (AA) and efferent (EA) arteriolar diameters of rat kidneys were assessed using the blood-perfused juxtamedullary nephron technique. The Cox-2 inhibitor NS-398 (10 microM) 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 constriction was prevented after interruption of distal delivery by transection of the loops of Henle. The effect was selective for AAs since NS-398 did not influence EAs of untreated or acetazolamide-treated kidneys. Pretreatment with the nNOS inhibitor S-methyl-L-thiocitrulline (10 microM) prevented the NS-398-induced AA constriction observed during acetazolamide treatment. Although we previously demonstrated that acetazolamide treatment enhanced AA constrictor response to S-methyl-L-thiocitrulline, the enhancement by acetazolamide was inhibited by pretreatment with 10 microM NS-398 (16.4 +/- 1.9 and 15. 0 +/- 0.5% with and without acetazolamide, respectively, P > 0.05). These results indicate that, during increased activation of TGF-dependent vasoconstrictor signals, Cox-2 generates vasodilatory metabolites in response to increased nNOS activity and thus participates in the counteracting modulation of TGF-mediated AA constriction.

Author List

Ichihara A, Imig JD, Inscho EW, Navar LG

MESH terms used to index this publication - Major topics in bold

Acetazolamide
Animals
Arterioles
Citrulline
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Feedback
Isoenzymes
Juxtaglomerular Apparatus
Kidney Tubules
Kinetics
Loop of Henle
Male
Muscle Tonus
Muscle, Smooth, Vascular
Nephrons
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitrobenzenes
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Sulfonamides
Thiourea
Vasoconstriction