CHRONIC SODIUM-POTASSIUM-ATPASE INHIBITION WITH OUABAIN IMPAIRS RENALHEMODYNAMICS AND PRESSURE NATRIURESIS IN THE RAT

1. Chronic Na+,K+-ATPase inhibition with ouabain induces hypertension in the rat, To examine the role of the kidney in this process, the eff ect of changes in renal perfusion pressure on glomerular filtration ra te, renal blood flow and urinary sodium excretion were determined in r ats treated intraperitoneally with ouabain (27.8 mu g day(-1) kg(-1) b ody weight) or vehicle for 6 weeks. 2. After ouabain administration, b aseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151+/-2 mmHg; n = 9) than in control rats (116+/ -4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerula r filtration rate was significantly lower (P < 0.05) in ouabain-treate d rats compared with control rats. Glomerular filtration rate was 721/-73 mu l/min at 150 mmHg, and fell significantly to 322+/-64 mu l/min at 100 mmHg. In the control group, glomerular filtration rate was wel l autoregulated. The glomerular filtration rate autoregulatory index w as calculated to determine the ability to maintain glomerular filtrati on rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; > 1 reflects the absence of autoregulation), This ind ex was greater in the ouabain group than in the control group (1.54+/- 0.2 compared with 0.29+/-0.2; P < 0.05), Renal blood flow showed a sim ilar pattern. 4. Absolute urinary sodium excretion rate was less in ou abain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodi um excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1+/-57.1 compared with 82.1+/-14.8 mu mol min(-1) mmHg(-1)). 5. Thus, chronic inhibition of Na+,K+-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in t he pressure natriuresis relationship, such that a 25-30 mmHg higher re nal perfusion pressure is necessary to excrete any given sodium load, These abnormalities may contribute to the development and maintenance of hypertension in this model.