NULL MUTATION OF THE NADPH OXIDASE SUBUNIT p67PHOXPROTECTS THE DAHL-S RAT FROMSALT-INDUCED REDUCTIONS IN MEDULLARY BLOOD FLOW AND GFR

Null mutations in the p67 phox subunit of NADPH-oxidase confer protection from salt-sensitivity on Dahl salt-sensitive (SS) rats. Here we track the sequential changes in medullary blood flow, glomerular filtration rate, urinary protein and mean arterial pressure in SS p67 phox null rats and wild-type littermates during 21-days of 4.0% NaCl (high-salt [HS]) diet. Optical fibers were implanted in the renal medulla and medullary blood flow measured in conscious rats by laser-Doppler flowmetry. Separate groups of rats were prepared with femoral venous catheters and glomerular filtration rate measured by the transcutaneous assessment of fluorescein isothiocyanate-sinistrin disappearance curves. Mean arterial blood pressure was measured by telemetry. In wild-type rats HS caused a rapid reduction in medullary blood flow which was significantly lower than control values by HS day-6. Reduced medullary blood flow was associated with a progressive increase in mean arterial pressure, averaging 170 ± 5 mmHg by HS salt day-21. A significant reduction in glomerular filtration rate was evident at day-14 HS, after the onset of hypertension and reduced medullary blood flow. In contrast, HS had no significant effect on medullary blood flow in SS p67 phox null rats and the pressor response to sodium was blunted, averaging 150 ± 3 mmHg at day-21 HS. Glomerular filtration rate was maintained throughout the study and proteinuria was reduced. In summary, when p67 phox is not functional in the SS rat HS does not cause reduced medullary blood flow and salt-sensitive hypertension is attenuated, consequently renal injury is reduced and glomerular filtration rate is maintained.