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

Acute unilateral renal denervation (aDNX) is associated with reduced tubuloglomerular feedback (TGF) sensitivity. Six days after denervation (cDNX) TGF sensitivity is somewhat restored, but TGF reactivity increased. This study aimed to investigate if the increased TGF reactivity that was seen in cDNX kidneys was owing to reduced production of nitric oxide (NO). TGF characteristics were determined with micropuncture experiments in anaesthetized rats, using the stop-flow pressure (PSF) technique. Maximal drop in PSF (ΔPSF) was used as an index of TGF reactivity and the loop of Henle perfusion rate that elicited half-maximal ΔPSF, the turning point (TP) was used 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 clearly lower than in aDNX rats (37.3 ± 3.1 nL min -1 ). TGF was more reactive in cDNX rats (ΔPSF = 14.7 ± 1.1 mmHg) than in aDNX (7.9 ± 1.1 mmHg) and control rats (9.6 ± 0.9 mmHg) Intratubular inhibition of NO synthase N ω -nitro-L-arginine (L-NA) in sham-DNX animals, decreased TP to 13.9 ± 2.2 nL min -1 and ΔPSF was increased with 92%. In cDNX kidneys TP was not significantly reduced by L-NA, and TGF reactivity was only moderately increased by 31%. Intratubular infusion of L-arginine (L-Arg) reduced ΔPSF from 10.2 ± 0.7 to 6.5 ± 0.6 mmHg in sham-DNX kidneys, but TP was unaffected. In cDNX kidneys, there was no effect on either ΔPSF or TP by the addition of L-Arg. However, when NO was delivered via sodium nitroprusside in the tubular perfusate, a clear reduction of ΔPSF was seen in both sham-DNX and cDNX kidneys (from 9.9 ± 0.5 to 4.4 ± 1.0 and from 14.9 ± 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 resets TGF to a higher sensitivity and more pronounced reactivity.