Abstract
Hypertension is an increase of blood pressure to levels greater than normal that arises because of a mismatch between the volume of the vascular tree and the volume of blood. Blood volume depends on total body sodium content, which is a balance between sodium intake and output. Total body sodium is controlled by variable excretion of sodium by the kidneys. To regulate sodium balance, the primary variable that the kidney monitors is not total body sodium, but rather systemic blood pressure. Renal regulation of blood pressure is via the release of the peptide hormone, renin from specialized renal cells. Release of renin ultimately leads to the production of angiotensin II. Angiotensin II increases total peripheral resistance and blood pressure and also leads to an increase in aldosterone. Aldosterone is a steroid hormone that increases sodium reabsorption in the distal nephron by activating epithelial Na channels (ENaCs). Thus, Hypertension is a defect in one of these elements that control total body sodium balance.
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Al-Baldawi NF, Eaton DC. Aldosterone activates isoprenyl methyltrans-ferase in A6 epithelia by serine phosphorylation. FASEB J 2001;15: A432, abstract.
Al-Baldawi NF, Stockand JD, Al Khalili OK, Yue G, Eaton DC. Aldosterone induces Ras methylation in A6 epithelia. Am J Physiol Cell Physiol 2000;279(2):C429–C439.
Becchetti A, Kemendy AE, Stockand JD, Sariban-Sohraby S, Eaton DC. Methylation increases the open probability of the epithelial sodium channel in A6 epithelia. J Biol Chem 2000;275(22): 16,550–16,559.
Canessa CM, Horisberger JD, Rossier BC. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature 1993;361:467–470.
Canessa CM, Schild L, Buell G, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 1994;367: 463–467.
Corvol P, Persu A, Gimenez-Roqueplo AP, Jeunemaitre X. Seven lessons from two candidate genes in human essential hypertension: angiotensinogen and epithelial sodium channel. Hypertension 1999; 33(6):1324–1331.
Goulet CC, Volk KA, Adams CM, Prince LS, Stokes JB, Snyder PM. Inhibition of the epithelial Na+channel by interaction of Nedd4 with a PY motif deleted in Liddle’s syndrome. J Biol Chem 1998;273(45): 30,012–30,017.
Grunder S, Zagato L, Yagil C, Yagil Y, Sassard J, Rossier BC. Polymorphisms in the carboxy-terminus of the epithelial sodium channel in rat models for hypertension. J Hypertens 1997;15(2):173–179.
Hummler E. Epithelial sodium channel, salt intake, and hypertension. Curr Hypertens Rep 2003;5(1):11–18.
Hummler E, Horisberger JD. Genetic disorders of membrane transport. V. The epithelial sodium channel and its implication in human diseases. Am J Physiol 1999;276:G567–G571.
Kamynina E, Staub O. Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na(+) transport. Am J Physiol Renal Physiol 2002; 283(3):F377–F387.
Lingueglia E, Voilley N, Waldmann R, Lazdunski M, Barbry P. Expression cloning of an epithelial amiloride-sensitive Na+channel. A new channel type with homologies to Caenorhabditis elegans degener-ins. FEBS Lett 1993;318:95–99.
Malik B, Schlanger L, Al Khalili O, Bao HF, Yue G, Price SR, et al. ENaC degradation in A6 cells by the ubiquitin-proteosome proteolytic pathway. J Biol Chem 2001;276(16):12,903–12,910.
Matsubara M. Genetic determination of human essential hypertension. Tohoku J Exp Med 2000;192(1):19–33.
Pearce D. The role of SGK1 in hormone-regulated sodium transport. Trends Endocrinol Metab 2001;12(8):341–347.
Pratt JH, Ambrosius WT, Agarwal R, Eckert GJ, Newman S. Racial difference in the activity of the amiloride-sensitive epithelial sodium channel. Hypertension 2002;40(6):903–908.
Rossier BC, Pradervand S, Schild L, Hummler E. Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors. Annu Rev Physiol 2002;64:877–897.
Schafer JA. Abnormal regulation of ENaC: syndromes of salt retention and salt wasting by the collecting duct. Am J Physiol Renal Physiol 2002;283(2):F221–F235.
Schild L. The ENaC channel as the primary determinant of two human diseases: Liddle syndrome and pseudohypoaldosteronism. Nephrologie 1996;17(7):395–400.
Staub O, Abriel H, Plant P, Ishikawa T, Kanelis V, Saleki R, et al. Regulation of the epithelial Na+channel by Nedd4 and ubiquitination. Kidney Int 2000;57(3): 809–815.
Stockand JD, Al-Baldawi NF, Al Khalili OK, Worrell RT, Eaton DC. S-adenosyl-L-homocysteine hydrolase regulates aldosterone-induced Na+transport. J Biol Chem 1999;274(6):3842–3850.
Stockand JD, Edinger RS, Al-Baldawi NF, et al. Isoprenylcysteine-O-carboxyl methyltransferase regulates aldosterone-sensitive Na+reab-sorption. J Biol Chem 1999;274(38):26,912–26,916.
Stockand JD, Edinger RS, Eaton DC, Johnson JP. Toward understanding the role of methylation in aldosterone-sensitive Na(+) transport. News Physiol Sci 2000;15:161–165.
Warnock DG. Aldosterone-related genetic effects in hypertension. Curr Hypertens Rep 2000;2(3):295–301.
Yue G, Malik B, Yue G, Eaton DC. Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells. J Biol Chem 2002;277(14): 11,965–11,969.
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Eaton, D.C., Malik, B., Ma, HP. (2006). Hypertension and Sodium Channel Turnover. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Medicine. Humana Press. https://doi.org/10.1007/978-1-59259-963-9_59
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DOI: https://doi.org/10.1007/978-1-59259-963-9_59
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