Impaired effect by NO synthase inhibition on tubuloglomerular feedback in rats after chronic renal denervation

Acute unilateral renal denervation (aDNX) is associated with reduced tubulo glomerular feedback (TGF) sensitivity. Six days after denervation (cDNX) TG F sensitivity is somewhat restored, but TGF reactivity increased. This stud y aimed to investigate if the increased TGF reactivity that was seen in cDN X kidneys was owing to reduced production of nitric oxide (NO). TGF charact eristics were determined with micropuncture experiments in anaesthetized ra ts, using the stop-flow pressure (PSF) technique. Maximal drop in PSF (Delt a PSF) was used as an index of TGF reactivity and the loop of Henle perfusi on rate that elicited half-maximal Delta PSF, the turning point (TP) was us ed as a measure of TGF sensitivity. In cDNX kidneys, TP was higher than in control rats (25.4 +/- 1.5 nL min(-1) vs. 19.1 +/- 1.1 nL min(-1)), but cle arly lower than in aDNX rats (37.3 +/- 3.1 nL min(-1)). TGF was more reacti ve in cDNX rats (Delta PSF = 14.7 +/- 1.1 mmHg) than in aDNX (7.9 +/- 1.1 m mHg) and control rats (9.6 +/- 0.9 mmHg). Intratubular inhibition of NO syn thase N-omega-nitro-L-arginine (L-NA) in sham-DNX animals, decreased TP to 13.9 +/- 2.2 nL min(-1) and Delta PSF was increased with 92%. In cDNX kidne ys TP was not significantly reduced by L-NA, and TGF reactivity was only mo derately increased by 31%. Intratubular infusion of L-arginine (L-Arg) redu ced Delta PSF from 10.2 +/- 0.7 to 6.5 +/- 0.6 mmHg in sham-DNX kidneys, bu t TP was unaffected. In cDNX kidneys, there was no effect on either Delta P SF or TP by the addition of L-Arg. However, when NO was delivered via sodiu m nitroprusside in the tubular perfusate, a clear reduction of Delta PSF wa s seen in both sham-DNX and cDNX kidneys (from 9.9 +/- 0.5 to 4.4 +/- 1.0 a nd from14.9 +/- 1.3 to 8.1 +/- 1.5 mmHg, respectively). This indicates that cDNX is a state of low renal NO production and that this low level of NO r esets TGF to a higher sensitivity and more pronounced reactivity.