Inhibition of macula densa-stimulated renin secretion by pharmacological blockade of cyclooxygenase-2.
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 to 26.1 +/- 7.4 nGU/min (P < 0.01, n = 19). The presence of the COX-1 inhibitor valerylsalicylate (500 microM) 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 microM) 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 tubuloglomerular contact area are a likely source of prostaglandins participating in the signaling pathway between the macula densa and renin-producing granular cells.
Traynor
T R
TR
University of Michigan Medical School, Department of Physiology, Ann Arbor, Michigan 48109, USA.
Smart
A
A
Briggs
J P
JP
Schnermann
J
J
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000187:drug effects*; D007606:Juxtaglomerular Apparatus / Q000502:physiology*; D007686:Kidney Tubules, Distal / Q000502:physiology*; D009578:Nitrobenzenes / Q000494:pharmacology; D009994:Osmolar Concentration; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011817:Rabbits; D012083:Renin / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000092502:Renin Inhibitors
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D012459:Salicylates; D012965:Sodium Chloride; D013449:Sulfonamides; D000092502:Renin Inhibitors; C401835:valerylsalicylate; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide