Temporal adaptation of tubuloglomerular feedback: Effects of COX-2

Abstract

Reductions in proximal reabsorption cause increases in delivery of sodium chloride to the macula densa (MD), which activates the tubuloglomerular feedback (TGF) mechanism and reduces glomerular filtration rate. TGF undergoes temporal adaptation, permitting filtration rate to rise in spite of elevated MD delivery of NaCl. Inhibitors of nitric oxide synthase I (NOS I) prevent TGF adaptation, but angiotensin-converting enzyme inhibitors have no effect. COX-2 activity moves in parallel with changes in NOS I and intrarenal renin. We examined the impact of COX-2 inhibition on TGF temporal adaptation and effects of inhibition of COX-2 and NOS I on plasma and kidney angiotensin II (Ang II). Kidney blood flow (RBF) and glomerular filtration rate (GFR) were measured before and during benzolamide (BNZ) infusion in control Wistar rats and rats concurrently receiving COX-2 inhibitors. Plasma and kidney angiotensin II content was evaluated by radioimmunoassay in control rats, rats after 60 minutes of BNZ, and during COX-2 and NOS-1 inhibition after BNZ. BNZ reduced both RBF and GFR in all groups. During BNZ, RBF and GFR returned to normal control values within 60 minutes. COX-2 inhibitors totally prevented TGF adaptation. Plasma and kidney Ang II did not change after BNZ, and NOS I and COX-2 inhibitors had no effect on plasma or intrarenal Ang II. Within 1 hour after BNZ, rats undergo TGF temporal adaptation. Administration of COX-2 inhibitors prevented TGF temporal adaptation, identical to the effect of NOS I inhibition. Changes in intrarenal Ang II cannot explain this prevention of TGF temporal adaptation.