title: The alpha1-Na/K pump does not mediate the involvement of ouabain in the development of hypertension in rats.
abstract: The Na/K pump of vascular smooth muscle cells (VSMC) and renal epithelial cells (REC) is viewed as a target of digitalis and endogenous ouabain (EO), leading to the development of hypertension. In this study, we compared the effect of ouabain on Na/K pump activity and the intracellular content of monovalent cations in VSMC and REC obtained from rats, humans and dogs. In VSMC from the rat aorta, ouabain inhibited maximal Na/K pump activity measured as the rate of 86Rb influx in Na+-loaded cells, with an ID50 of approximately 20-30 microM without any differences between two strains of normotensive rats (WKY and BN.1x) and three substrains of spontaneously hypertensive rats (SHR). Half-maximal inhibition of the Na/K pump in REC from the rat inner medullary collecting duct was observed at approximately 20 microM of ouabain. In contrast to rat cells, half-maximal inhibition of 86Rb influx in VSMC from human coronary arteries and in REC from the Madin-Darby canine kidney was seen at approximately 0.03 and 0.1 microM ouabain, respectively. At concentrations lower than 100 microM, ouabain did not affect the intracellular content of exchangeable Na+ and K+ in rat VSMC, measured as the steady-state distribution of 22Na and 86Rb, whereas in human VSMC, it increased the intracellular Na+/K+ ratio with an ID50 of approximately 0.5 microM. Keeping in mind that the circulating level of administered digitalis and EO does not exceed 10(-9) M, our results strongly suggest that the involvement of these compounds in the pathogenesis of hypertension in rats is not mediated by inhibition of the alpha1-isoform of the Na/K pump in VSMC and REC. Alternative mechanisms of the involvement of EO and ouabain-like factors in the development of hypertension are considered.
authors.affiliation: Centre de recherche, Centre hospitalier de l'Université de Montréal--Hĵtel-Dieu, PQ, Canada. sergei.n.orlov@umontreal.ca
authors.forename: Sergei N
authors.initials: SN
authors.lastname: Orlov
authors.forename: Sebastien
authors.initials: S
authors.lastname: Taurin
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
mesh_terms: D000818:Animals; D001011:Aorta; D002414:Cations, Monovalent / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000209:etiology*; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D007668:Kidney; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D002414:Cations, Monovalent; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010042:Ouabain; C499076:ATP1A1 protein, human; C499075:Atp1a1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase