The goal of this project is to identify the cellular basis of a likely tubular transport abnormality (either intrinsic to the kidney or an abnormal response to regulatory humoral agents) which leads to inappropriate sodium retention in experimental animal models of hypertension. The assumption underlying this project is that the presumed membrane defect is expressed in a disturbance of the cellular homeostasis of renal cells and, therefore, should be detectable by intracellular concentration measurements. For determination of electrolyte concentrations in individual tubular cells, or even subcellular structures, we will employ the technique of electron microprobe analysis. The analyses will be performed on thin frozen-dried cryosections obtained from fresh, shock-frozen tissue samples. Initially, only short, non-perfused isolated nephron segments will be used as specimen. Later, we will attempt to obtain longer segments which can be perfused prior to freezing under in vitro conditions. For this purpose, we will develop a technique which allows rapid freezing of the tubules while being perfused. Using these methods, we will first study the cellular electrolytes composition of different tubular segments obtained from two different models of genetically fixed hypertension. Second, we will examine the effect of high and normal NaC1-containing diets in different animal models. Third, we will investigate the possibility of an abnormal responsiveness to modulators of tubular Na transport. This project will be closely integrated with the transport studies of Projects 2, 3, 4 and 8.

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University of Alabama Birmingham
United States
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Chambrey, R; Achard, J M; St John, P L et al. (1997) Evidence for an amiloride-insensitive Na+/H+ exchanger in rat renal cortical tubules. Am J Physiol 273:C1064-74
Wang, D; Balkovetz, D F; Warnock, D G (1995) Mutational analysis of transmembrane histidines in the amiloride-sensitive Na+/H+ exchanger. Am J Physiol 269:C392-402
Brown, S A; Finco, D R; Navar, L G (1995) Impaired renal autoregulatory ability in dogs with reduced renal mass. J Am Soc Nephrol 5:1768-74
Botero-Velez, M; Curtis, J J; Warnock, D G (1994) Brief report: Liddle's syndrome revisited--a disorder of sodium reabsorption in the distal tubule. N Engl J Med 330:178-81
Kudo, L H; Hawk, C T; Schafer, J A (1994) Sodium and water transport in cortical collecting duct of Dahl salt-resistant rat. Am J Physiol 267:F583-91
Lewis, J L; Warnock, D G (1994) Renal apical membrane sodium-hydrogen exchange in genetic salt-sensitive hypertension. Hypertension 24:491-8
Allon, M; Parris, M (1993) Calcitriol stimulates Na(+)-Pi cotransport in a subclone of opossum kidney cells (OK-7A) by a genomic mechanism. Am J Physiol 264:F404-10
Wuthrich, R P; Jenkins, T A; Snyder, T L (1993) Regulation of cytokine-stimulated vascular cell adhesion molecule-1 expression in renal tubular epithelial cells. Transplantation 55:172-7
Chen, P Y; St John, P L; Kirk, K A et al. (1993) Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation. Lab Invest 68:174-84
Wuthrich, R P; Sekar, P (1993) Effect of dexamethasone, 6-mercaptopurine and cyclosporine A on intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. Biochem Pharmacol 46:1349-53

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