Endogenous ouabain in renal Na(+) handling and related diseases.
The 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 α(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.
Scientific Institute San Raffaele, Università Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. manunta.paolo@hsr.it
Paolo
P
Manunta
Elisabetta
E
Messaggio
Nunzia
N
Casamassima
Guido
G
Gatti
Simona Delli
SD
Carpini
Laura
L
Zagato
John M
JM
Hamlyn
D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004232:Diuretics / Q000627:therapeutic use; D004330:Drosophila; D004837:Epinephrine / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006973:Hypertension; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D010042:Ouabain / Q000378:metabolism*; D051437:Renal Insufficiency / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D004232:Diuretics; D019831:Sodium-Calcium Exchanger; D000804:Angiotensin II; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D004837:Epinephrine