| This dissertation examined the hypothesis that there are long-term alterations in kidney function following ischemic acute renal failure. Such changes alter the ability of the kidney to regulate sodium excretion and lead to the development of sodium-sensitive hypertension.; This hypothesis was tested with the following specific aims: (1) To study the effect of ischemic acute renal failure on intrinsic renal mechanisms related to sodium excretion and hemodynamics. (2) To study the effect of ischemic acute renal failure and high sodium diet on blood pressure and manifestations of secondary renal disease. (3) To study the role of the interstitial inflammatory cells in development of sodium sensitive hypertension following apparent recovery from ischemic acute renal failure.; In aim 1, we further examined the functional effects of reduced renal microvascular density by studying renal hemodynamics and the pressure natriuresis relationship. In another set of studies, we measured renal interstitial hydrostatic pressure and found it is significantly reduced in post-ischemic animals compared to sham-operated controls. These observations demonstrate an alteration in the intrinsic mechanisms of sodium handling in the post-ischemic kidney.; In aim 2, we examined the effect of a high sodium diet on blood pressure, albuminuria, and fibrosis in male Sprague Dawley rats following ischemic acute renal failure. In addition, we examined the effects of a high salt diet on the development of tubulointerstitial disease and albuminuria. These studies indicate that acute renal failure (ARF) induced by I/R results in a defect in the normal ability to handle sodium, predisposing the development of hypertension and hastening the progression of secondary renal disease.; In aim 3, we examined the role of the infiltrating immune cells in the kidney during the development of sodium dependent hypertension and tubulointerstitial damage in male Sprague Dawley rats following ischemic acute renal failure. Post-ischemic animals treated with systemic immune suppression had less albuminuria and infiltrating myofibroblasts, fibroblasts, and macrophages in the renal interstitial space compared to post-ischemic vehicle treated animals. These studies indicate a potential role of the inflammatory system in the development of sodium dependent hypertension and secondary renal damage following ischemic renal injury.; In summary, we found alterations in the regulation of sodium excretion following I/R predisposing the development of hypertension and progressive renal disease in rats fed a high salt diet. Based on these studies, potential mechanisms of altered sodium handling may include decreased renal interstitial hydrostatic pressure, compromised hemodynamic responses, and infiltration of renal inflammatory cells. (Abstract shortened by UMI.)... |
