TGF and nitric oxide: effects of salt intake and salt-sensitive hypertension

Abstract

The tubuloglomerular feedback response (TGF) entails vasoconstriction of the afferent arteriole (AA) and a fall in the glomerular capillary pressure (PGC) and single nephron glomerular filtration rate (SNGFR) during NaCl reabsorption in the macula densa (MD) segment. Recent studies have concluded that nitric oxide (NO) is synthesized by the MD and blunts the TGF response. Since a high salt (HS) diet has been found to blunt TGF, we tested the effects of salt intake on the response to blockade of nitric oxide synthesis. For the first series, the TGF was assessed from changes in proximal stop-flow pressure (PSF, an index of PGC in response to graded perfusion of the loop of Henle (LH) with name tubular fluid (NTF). Loop perfusion with 10(-3) M L-NMA did not affect the PSF responses of low salt (LS) rats, but reduced (P < 0.01) the PSF of HS rats during perfusion at 20 nl.min-1 (-1.5 +/- 0.4 mm Hg; P < 0.01) and at 40 nl.ml-1 (-2.2 +/- 0.5 mm Hg; P < 0.001). For the second series, the TGF responses of salt sensitive Dahl/Rapp (ssDR) rats were compared to Sprague-Dawley (SD) rats. Both groups were studied 8 to 10 days after starting HS or LS diets by loop perfusion of artificial tubular fluid at 40 nl.min-1. Compared to Sprague-Dawley rats, the ssDR had blunted maximal TGF responses during LS (SD, 8.2 +/- 0.3 vs. ssDR, 6.4 +/- 0.3 mm Hg; P < 0.001), but not during HS. During LS intake, addition of L-NMA to ATF perfusing the loop of Henle did not alter the maximal TGF response of either strain. However, during HS intake L-NMA increased the maximal TGF response of SD rats (4.4 +/- 0.4 to 6.7 +/- 0.5 mm Hg; P < 0.001) but did not significantly change the PSF of ssDR rats (5.2 +/- 0.3 to 5.7 +/- 0.5 mm Hg; NS). We conclude that the TGF response is enhanced by blockade of NOS during HS, but not LS intakes; this response to NOS blockade during HS intake is lost in salt sensitive Dahl/Rapp rats.