Immunological Identification of Na,K‐ATPase Isoforms in Nonfailing and Failing Myocardium<sup>a</sup>

Barbey, Odile; Gerbi, Alain; Robert, Karine; Mayol, Vincent; Pierre, Sandrine V.; Paganelli, Franck; Maixent, Jean-Michel

doi:10.1111/j.1749-6632.1997.tb52342.x

Cited by 5 publications

(1 citation statement)

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“…In this model, the expression of Na/K-ATPase and kinetics of digitalis association/dissociation are significantly more like that of human than is the rat (3, 26). The goals of the study were to determine 1) whether an ouabain induced increase in cardiac inotropy is accompanied by activation of the cardiac Na/K-ATPase signaling cascade, and 2) if sub-inotropic doses of ouabain protects against ischemic injury in the rabbit heart, a species with high cardiac Na/K-ATPase sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Preconditioning by Subinotropic Doses of Ouabain in the Langendorff perfused Rabbit Heart

Morgan¹,

Li²,

Stebal³

et al. 2010

Journal of Cardiovascular Pharmacology

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Short exposure to low concentrations of digitalis drugs like ouabain protects the rat heart against ischemia/reperfusion injury through the activation of the Na/K-ATPase/c-Src receptor complex and subsequent stimulation of key intracellular cardioprotective signals. Rat Na/K-ATPase, however, is relatively insensitive to digitalis, and it is not known if similar results could be obtained in species with higher sensitivity. Thus, to determine whether ouabain pretreatment protects against ischemic injury and activates the Na/K-ATPase signaling cascade in a species with a cardiac glycoside sensitivity comparable to humans, the present study was conducted in the rabbit model. In Langendorff-perfused rabbit hearts, 20 min exposure to 500 nM ouabain resulted in positive inotropy as evidenced by a significant increase in +dP/dt, and this increase was accompanied by the activation of several well-characterized downstream mediators of the cardiac Na/K-ATPase receptor pathway, including Src, Akt, ERK1/2, and PKCε. A short (4 min) administration of a sub-inotropic dose of ouabain (100 nM) followed by an 8 min washout before 30 min of global ischemia and 120 min of reperfusion resulted in protection against cell death, as evidenced by a significant decrease in infarct size. These data indicate that ouabain administration activates the Na/K-ATPase signaling cascade and protects against ischemic injury in a species with high cardiac Na/K-ATPase sensitivity.

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Section: Introductionmentioning

confidence: 99%

Preconditioning by Subinotropic Doses of Ouabain in the Langendorff perfused Rabbit Heart

Morgan¹,

Li²,

Stebal³

et al. 2010

Journal of Cardiovascular Pharmacology

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Maixent

Lelièvre

Berrebi-Bertrand

1998

Cardiovascular Drugs and Therapy

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LND-623 is a new aminosteroid analog of ouabain, with a greater separation between efficacy and toxicity than ouabain. To determine its mechanism of action, we studied its biochemical and physiological effects on human red blood cell sodium transports on different cellular structures regarded as sites of contractile control, and we compared its relative efficacy to ouabain in rat heart preparations and membrane-bound Na, K-ATPase isoenzymes. The response to ouabain was evaluated in Langendorff-perfused hearts and on purified membrane-bound Na, K-ATPase. LND-623 is 6.8-fold more efficient than ouabain in inhibiting the human Na+ pump (IC50 = 0.098 +/- 0.001 microM vs. 0.67 +/- 0.02 microM); (P < 0.0001). LND-623 had no effect on the following cellular functions: Na-Ca exchange, Na-K cotransport, Ca-ATPase, slow calcium channels, adenylate cyclase system, phosphodiesterase, and calcium sensitivity of the contractile protein system. The dose-response curve for the positive inotropic and inhibitory effects on rat cardiac isoenzymes produced by LND-623 were clearly biphasic. The amplitude of the maximum inotropic effect, without any toxic effect, was up to three-fold higher with LND-623 than with the same maximum dose of ouabain used. The strong positive inotropic effect of LND-623 in rats could be related to a specific inhibition of the two rat cardiac isoforms of the Na, K-ATPase.

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REMODELING OF Na,K-ATPase, AND MEMBRANE FLUIDITY AFTER ATRIAL FIBRILLATION IN SHEEP

Maixent

Duran

Pierre

et al. 2002

Journal of Receptors and Signal Transduction

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Immunological Identification of Na,K‐ATPase Isoforms in Nonfailing and Failing Myocardium^a

Cited by 5 publications

References 2 publications

Preconditioning by Subinotropic Doses of Ouabain in the Langendorff perfused Rabbit Heart

Preconditioning by Subinotropic Doses of Ouabain in the Langendorff perfused Rabbit Heart

Untitled

REMODELING OF Na,K-ATPase, AND MEMBRANE FLUIDITY AFTER ATRIAL FIBRILLATION IN SHEEP

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Immunological Identification of Na,K‐ATPase Isoforms in Nonfailing and Failing Myocardiuma

Cited by 5 publications

References 2 publications

Preconditioning by Subinotropic Doses of Ouabain in the Langendorff perfused Rabbit Heart

Preconditioning by Subinotropic Doses of Ouabain in the Langendorff perfused Rabbit Heart

Untitled

REMODELING OF Na,K-ATPase, AND MEMBRANE FLUIDITY AFTER ATRIAL FIBRILLATION IN SHEEP

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Immunological Identification of Na,K‐ATPase Isoforms in Nonfailing and Failing Myocardium^a