Abstract
Prolonged stimulation with adrenocorticotropic hormone (ACTH) causes hypertension and increases Na+ intake and urine output in humans and animals. However, its biochemical basis remains to be established. Since renal Na+/H+ exchanger isoforms (NHE) and the sodium pump play an important role in this condition, their levels were examined in rats stimulated with ACTH. Male Wistar rats received daily sc injection of ACTH (30 µg/100 g of body wt) for 4 d. Half of the ACTH-stressed rats were kept for four additional days without injection of ACTH (poststimulation). In a third group, the animals were treated with dexamethasone (50 µg/100 g of body wt) daily for 4 d. A fourth group consisted of unstressed control animals. Levels of NHE proteins were measured by Western blot analysis. Sodium pump activity was assessed by the level of ouabain-sensitive K-stimulated p-nitrophenylphosphatase activity (PNP) in the renal cortex. ACTH caused a selective decrease in NHE-3, but not of NHE-1 or α-actin levels. Interestingly, this ACTH-induced change was not duplicated in the animals treated with dexamethasone. Immunofluorescence data demonstrated that NHE-3 is located in the renal proximal tubules. PNP activity, on the contrary, was increased in both the ACTH-stimulated and dexamethasone-treated animals. More important, these changes in NHE-3 and PNP activity returned to the control level poststimulation. In conclusion, while PNP upregulation may be mediated by adrenocortical glucocorticoid, a role for glucocorticoids in the suppression of NHE-3 is less clear. These changes might impair renal tubular Na+ reabsorption and hence increase Na+ and water excretion in ACTH stimulation, thus acting as a counterbalance to normalize blood pressure in ACTH-stimulated animals.
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References
Checkley, S. (1996). Br. Med. Bull. 52, 597–617.
Kenyon, C. J. and Fraser, R. (1992). In: The adrenal gland. 2nd ed. James, V. H. T. (ed.). Raven: New York.
Whiteworth, J. A., Hewitson, T. D., Ming, L., Wilson, R. S., Scoggins, B. A., Wright, R. D., and Kincaid-Smith, P. (1990). J. Hypertens. 8, 27–36.
Li, M., Birchall, I., Kincaid-Smith, P. S., and Whitworth, J. A. (1992). J. Hypertens. 10, 1129–1136.
Denton, D. A., Coghlan, J. P., Fei, D. T., Mckinley, M., Nelson, J., Scoggins, B. A., Tarjan, E., Tregear, G. W., Tresham, J. J., and Weisinger, R. (1984). Clin. Exp. Hypertens. A 6, 403–415.
Denton, D. A., Blair-West, J. R., McBurnie, M. I., Miller, J. A., Weisinger, R. S., and Williams, R. M. (1999). Am. J. Physiol. 277, R1033-R1040.
Scoggins, B. A., Denton, D. A., Whitworth, J. A., and Coghlan, J. P. (1984). Clin. Exp. Hypertens. A 6, 599–646.
Ely, D. L., Thoren, P., Weigand, J., and Folkow, B. (1986). J. Hypertens. Suppl. 4, S306-S309.
Tarjan, E., Denton, D. A., and Weisinger, R. S. (1991). Brain Res. 542, 219–224.
Khan, I., Thomas, N., and Haridas, S. (2001). Mol. Cell. Biochem. 219, 153–161.
Orlowski, J., Kandasamy, R. A., and Shull, G. E. (1992). J. Biol. Chem. 267, 9331–9339.
Counillon, L. and Pouyssegur, J. (2000). J. Biol. Chem. 275, 1–4.
Huot, S. J. and Aronson, P. S. (1991). Diabetes Care 14, 521–535.
Ng, L. L., Jennings, S., Davies, J. E., and Quinn, P. A. (2000). Clin. Sci. (Colch) 98, 409–418.
Cheng, B. and Kowal, J. (1994). J. Lipid Res. 35, 1115–1121.
Magyar, C. E., Zhang, Y., Holstein-Rathlou, N. H., and McDonough, A. A. (2000). Am. J. Physiol. Renal Physiol. 279, F358-F369.
Touyz, R. M. and Schiffrin, E. L. (1999). Hypertension 34, 442–449.
Karmazyn, M., Gan, X. T., Humphreys, R. A., Yoshida, H., and Kusumoto, K. (1999). Circ. Res. 85, 777–786.
Muto, S., Nemoto, J., Ebata, S., Kawakami, K., and Asano, Y. (1998). Kidney Int. 54, 492–508.
Petershack, J. A., Nagaraja, S. C., and Guillery, E. N. (1999). Am. J. Physiol. 276, R1825-R1832.
Feraille, E. and Doucet, A. (2001). Physiol. Rev. 81, 345–418.
Lee, Y. C., Lin, H. H., and Tang, M. J. (1995). Am. J. Physiol. 268, F862-F867.
Celsi, G., Stahl, J., Wang, Z. M., and Nishi, A. (1992). Acta Physiol. Scand. 145, 85–91.
Cho, J. H., Musch, M. W., DePaoli, A. M., Bookstein, C. M., Xie, Y., Burant, C. F., Rao, M. C., and Chang, E. B. (1994). Am. J. Physiol. 267, C796-C803.
Anderson, J. M. and Dietschy, J. M. (1978). J. Biol. Chem. 253, 9024–9032.
Khan, I., Al-Yatama, M., and Nandakumaran, M. (1999). Biochem. Mol. Biol. Int. 47, 715–722.
Khan, I. (1999). Dig. Dis. Sci. 44, 1525–1530.
Khan, I. (2001). Arch. Biochem. Biophys. 391, 25–29.
Grover, A. K., Samson, S. E., and Lee, R. M. (1985). Biochim. Biophys. Acta 818, 191–199.
Laemmli, U. K. (1970). Nat. (Lond.) 227, 680–685.
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Khan, I., Cheng, B. Selective suppression of renal Na+/H+ exchanger isoform-3 by prolonged stimulation of rats with adrenocorticotropic hormone. Endocr 16, 189–194 (2001). https://doi.org/10.1385/ENDO:16:3:189
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DOI: https://doi.org/10.1385/ENDO:16:3:189