Roles of nitric oxide in renal sodium homeostasis

The L-arginine-nitric oxide pathway was assessed at the whole kidney and single nephron levels. Compared to rats adapted to a low salt diet (LS), those on a high salt (HS) diet had greater excretion of NO2 + NO3 and cGMP and a greater increase in renal vascular resistance during inhibition of NOS with L-NAME. Since we found that an antibody to a constitutive NOS stained macula densa cells specifically, we tested the function of the macula densa/afferent arteriolar NO signaling pathway by microperfusion techniques. L-NMA added to fluid perfusating the macula densa of normal rats led to dose-dependent reductions in glomerular capillary pressure (PGC) that were prevented by co-perfusion with L-arginine. L-NMA reduced PGC consistently in rats on a high salt (HS) diet but was ineffective in rats on a low salt (LS) diet. We tested the role of availability of the NOS substrate in determining local NO generation. Microperfusion of L-arginine led to increases in PGC that were greater in rats adapted to LS than HS diets. These data disclose a macula densa-afferent arteriolar NO signaling pathway that is promoted by HS. Restricted NO generation during LS can be reversed by L-arginine and therefore may entail limited arginine availability for generation of NO. These studies indicate an important potential role for the L-arginine NO pathway adapting kidney function to changes in salt intake.