NO GENERATION AND ACTION DURING CHANGES IN SALT INTAKE - ROLES OF NNOS AND MACULA DENSA

Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitri c oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that c hanges in NO generation via nNOS in the macula densa contribute to cha nges in whole kidney NO generation and action during alterations in sa lt intake. Groups of rats (n = 6-10) were equilibrated to high-salt (H S) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nit roindazole (7-NI; a relatively selective inhibitor of nNOS), or furose mide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 p lus NO3 (NOx) was increased during HS (LS: 9.0 +/- 0.5 vs. HS: 15.7 +/ - 0.8 mu mol/24 h; P < 0.001), but this difference was prevented by 7- NI (LS: 7.4 +/- 1.3 vs. HS: 9.4 +/- 1.6 mu mol/24 h; NS). During nonse lective blockade of NOS with NG-nitro-L-arginine methyl ester (L-NAME) , renal vascular resistance (RVR) increased more in HS than LS (HS: +1 60 +/- 17 vs. LS: +83 +/- 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-N I (HS: +28 +/- 6 vs. LS: +34 +/- 8%; NS) or F with volume replacement (HS: +79 +/- 11 vs. LS: +62 +/- 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action t hat depend on nNOS and macula densa solute reabsorption.