Cyclooxygenase-2 participates in tubular flow-dependent afferent
arteriolar tone: interaction with neuronal nos.
Ichihara, Atsuhiro, John D. Imig, Edward W. Inscho, and L. Gabriel
Navar.
Department of Physiology, Tulane University School of Medicine, New
Orleans, LA 70112-2699
APStracts 5:0124F, 1998.
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 arteriolar (EA) diameters of rat kidneys were
assessed using the blood-perfused juxtamedullary nephron technique.
The COX-2 inhibitor, NS398 (10 _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
NS398-induced AA constriction was prevented following interruption of
distal delivery by transection of the loops of Henle. The effect was
selective for AAs since NS398 did not influence EAs of untreated or
acetazolamide-treated kidneys. Pretreatment with the nNOS inhibitor,
S-methyl-L-thiocitrulline (10 _M), prevented the NS398-induced AA
constriction observed during acetazolamide treatment. While 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 _M NS398 (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.
Received 6 May 1998; accepted in final form 9 July 1998.
APS Manuscript Number F107-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 30 July 1998