Evaluation of the role of the NAD(P)H oxidase subunit p67phox in the regulation of medullary blood flow in Dahl S rats

Abstract

Studies were performed in male Dahl salt‐sensitive rats (SS; SS/JrHsdMcwi) and SS rats with a null mutation in the p67phox gene (SSp67phox null mutant; SS‐Ncf2em1Mcwi+/+) aged 10–12 weeks (n=5/group) and maintained from birth on a 0.4% NaCl diet (LS). Optical fibers were implanted in the renal medulla and medullary blood flow (MBF) measured in the conscious animal by laser‐Doppler flowmetry. Mean arterial pressure (MAP) was measured from indwelling carotid catheters by telemetry. Following a 7 day recovery from surgery, baseline measurements of MAP and MBF were made daily to obtain 3 stable control days on LS. Rats were then switched to 4% NaCl diet (HS) and MAP and MBF measured over 7 days. During the LS period, MAP was comparable between SS (127±2mmHg) and p67phox null (121±3mmHg) rats. HS caused a rapid and sustained decrease in MBF in SS rats which was significantly different from LS by day 2 (reduction of 23±4%, p<0.05). Reduced MBF was associated with a progressive increase in MAP which averaged 149±4mmHg at day 7. HS had no significant effect on MBF in SSp67phoxnull rats and the pressor response was blunted, MAP averaged 133±8mmHg at day 7. In summary, when p67phox is not functional in the SS rat HS does not affect MBF and salt‐sensitive hypertension is attenuated. This suggests that p67phox contributes to the increased oxidative stress in the renal medulla associated with salt induced hypertension.