Inhibition of macula densa-stimulated renin secretion
bypharmacological blockade of cyclooxygenase-2.
Traynor, Timothy R., Ann Smart, Josephine P. Briggs, and Jurgen
Schnermann.
The University of Michigan Medical School, Department of
Physiology, Ann Arbor, MI 48109, and National Institute of Diabetes
and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892
APStracts 6:0115F, 1999.
Previous results from our laboratory have shown that in the isolated
perfused juxtaglomerular apparatus nonselective inhibitors of
cyclooxygenase (COX) activity prevent the stimulation of renin
secretion by a reduction in luminal NaCl concentration at the macula
densa. The present studies were performed to examine which COX
isoform is involved in NaCl-dependent renin secretion. In the absence
of COX inhibitors a reduction in luminal NaCl (from Na 141/Cl 120 mM
to Na 26/Cl 7 mM) caused an increase in renin secretion rate from 4.5
+ 1.8 nGU/min to 26.1 + 7.4 nGU/min (p < 0.01, n=19). The presence
of the COX-1 inhibitor valerylsalicylate (500 M) in lumen and bath
did not affect the stimulation of renin secretion by a reduction in
luminal NaCl concentration (5 + 1.8 nGU/min at high NaCl, and 30.5 +
9.4 nGU/min at low NaCl; p < 0.01, n=8). In contrast, the specific
COX-2 inhibitor NS-398 (50 M) in lumen and bath abolished the
stimulating effect of low luminal NaCl (12.8 + 3.9 nGU/min at high
NaCl, and 10.7 + 3.1 nGU/min at low NaCl; NS, n=15). The finding that
COX-2 is critically involved in macula densa control of renin
secretion indicates that the COX-2 expressing epithelial cells in the
tubulo-glomerular contact area are a likely source of prostaglandins
participating in the signaling pathway between the macula densa and
renin-producing granular cells.
Received 23 March 1999; accepted in final form 11 June 1999.
APS Manuscript Number F079-9.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999