Human　blood　pressure　salt　sensitivity　is　associated　with　changes　in　urinary　metabolites　related　to　fumarase　(Fh)　and　nitric　oxide　(NO)　metabolism,　and　fumarase　promotes　NO　production　through　an　arginine　regeneration　pathway.　We　examined　the　role　of　the　fumarase-NO　pathway　in　the　development　of　hypertension　using　genetically　engineered　rat　models.　Dahl　salt-sensitive　(SS)　rats　with　heterozygous　mutation　of　eNOS　(endothelial　NO　synthase　or　Nos3;　SS-Nos3(+/-))　were　bred　with　SS　rats　with　a　hemizygous　Fh　transgene.　SS-Nos3(+/-)　rats　without　the　Fh　transgene　(SS-Nos3(+/-)/Fh(0/0))　developed　substantial　hypertension　with　a　mean　arterial　pressure　of　134.2　+/-　3.7　mm　Hg　on　a　0.4%　NaCl　diet　and　178.0　+/-　3.5　mm　Hg　after　14　days　on　a　4%　NaCl　diet.　Mean　arterial　pressure　decreased　remarkably　to　123.1　+/-　1.4　mm　Hg　on　0.4%　NaCl,　and　143.3　+/-　1.5　mm　Hg　on　4%　NaCl　in　SS-Nos3(+/-)　rats　with　a　Fh　transgene　(SS-Nos3(+/-)/Fh(0/1)),　and　proteinuria,　renal　fibrosis,　and　tubular　casts　were　attenuated　in　SS-Nos3(+/-)/Fh(0/1)　rats　compared　with　SS-Nos3(+/-)/Fh(0/0)　rats.　eNOS　protein　abundance　decreased　in　rats　with　the　Nos3　heterozygous　mutation,　which　was　not　influenced　by　Fh　overexpression　in　rats　on　the　0.4%　NaCl　diet.　However,　the　decrease　in　NO　metabolite　in　the　renal　outer　medulla　of　SS-Nos3(+/-)/Fh(0/0)　rats　on　the　0.4%　NaCl　diet　was　reversed　in　SS-Nos3(+/-)/Fh(0/1)　rats,　and　levels　of　L-arginine,　but　not　the　other　12　amino　acids　analyzed,　were　significantly　higher　in　SS-Nos3(+/-)/Fh(0/1)　rats　than　in　SS-Nos3(+/+)/Fh(0/0)　rats.　In　conclusion,　fumarase　has　potent　effects　in　restoring　NO　production　and　blunting　the　development　of　hypertension　attributable　to　eNOS　haploinsufficiency.