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Endogenous ouabain in renal Na(+) handling and related diseases Manunta P; Messaggio E; Casamassima N; Gatti G; Carpini SD; Zagato L; Hamlyn JMBiochim Biophys Acta 2010[Dec]; 1802 (12): 1214-8The Na(+) pump and its Endogenous modulator Ouabain (EO) can be considered as an ancestral enzymatic system, conserved among species ranging from Drosophila to humans, related to Na handling. In this review, we examine how EO is linked with vascular function in hypertension and if it impacts the pathogenesis of heart and renal failure. Moreover, the molecular mechanism of endogenous ouabain-linked hypertension involves the sodium pump/sodium-calcium exchanger duet. Biosynthesis of EO occurs in adrenal glands and is under the control of angiotensin II, ACTH and epinephrine. Elevated concentrations of EO and in the sub-nanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure. Experimental data suggest that the Na/K-ATPase alpha(2)-catalytic subunit causes EO-induced vasoconstriction. Finally, maneuvers that promote Na depletion, as diuretic therapy or reduced Na intake, raise the EO levels. Taken together, these findings suggest a key role for EO in body Na homeostasis.|Adrenal Glands/metabolism/pathology[MESH]|Angiotensin II/metabolism[MESH]|Animals[MESH]|Cell Proliferation/drug effects[MESH]|Diuretics/therapeutic use[MESH]|Drosophila[MESH]|Epinephrine/metabolism[MESH]|Heart Failure/drug therapy/*metabolism/pathology/physiopathology[MESH]|Homeostasis/drug effects[MESH]|Humans[MESH]|Hypertension[MESH]|Kidney/*metabolism/pathology/physiopathology[MESH]|Myocytes, Cardiac/metabolism/pathology[MESH]|Myocytes, Smooth Muscle/metabolism/pathology[MESH]|Ouabain/*metabolism[MESH]|Renal Insufficiency/drug therapy/*metabolism/pathology/physiopathology[MESH]|Sodium-Calcium Exchanger[MESH]|Sodium-Potassium-Exchanging ATPase/*metabolism[MESH]|Sodium/*metabolism[MESH]|Vasoconstriction/drug effects[MESH] |
