How does ouabain influence hypertension?
Acute administration of ouabain promotes a positive inotropic effect (12) and increases blood pressure and the contraction of vascular smooth muscle (13,14). These findings suggest that ouabain increases vascular resistance and induces hypertension (Figure 1).
How does ouabain affect the heart?
Ouabain is a cardiac glycoside that acts by inhibiting the Na+/K+–ATPase sodium-potassium ion pump (but it is not selective). Once ouabain binds to this enzyme, the enzyme ceases to function, leading to an increase of intracellular sodium.
Do humans produce ouabain?
The human endogenous “ouabain” (EO) is a high affinity reversible inhibitor of the pump with inotropic and vasopressor activity. Circulating levels of EO depend upon the adrenal cortex and metabolic events preceding and following pregnenolone formation are involved in EO biosynthesis.
What is endogenous ouabain?
Endogenous Ouabain (EO) is cardiac glycoside acting as an adrenal stress hormone with cardiological, hemodynamic, and renal effects. This hormone increases to picomolar (10−12) range in the plasma of hypertensive humans [4. P. Manunta, P.
How does ouabain affect Na pump?
In cardiac cells, ouabain increases intracellular Ca2+ concentration and cardiac muscle contractility by inhibiting Na-K-ATPase activity, thus stimulating Na/Ca exchange (4). In some cells, however, ouabain at very low (pM to nM) concentrations increases Na-K-ATPase activity (23).
Why is ouabain toxic?
Cardenolides are steroids found in plant species all over the world. Many of them contain one or more glycone sugars and are recognized as toxic cardiac glycosides. Ouabain, a specific toxin from this group, has been studied for centuries due to its significant impact on heart disease.
How does ouabain cause death?
At low concentrations, ouabain selectively killed T98G cells. Knocking down the α3 subunit sensitized T98G cells to TMZ and caused more cell death.
What effect does ouabain have on the cell?
Ouabain binds, with high affinity and specificity, to the extracellular domain of the α-subunit of Na,K-ATPase. The binding inhibits the enzyme’s function, thereby altering the transmembrane electrochemical potential of the cell.
How does ouabain affect membrane potential?
The effect of ouabain on the resting membrane potential, therefore, was due to a change in the transmembrane potassium ion gradient. This, in turn, resulted from a decrease in intracellular potassium activity and, apparently, from an increased potassium activity at the cell surface.
What does ouabain do to a neuron?
Ouabain is well-known to prolong depolarization of neurons leading to osmolysis or calcium necrosis in brain tissues [8]. Upon ouabain binding, the Na, K-ATPase initiates a series of reactions that include interaction with neighboring proteins in what has been described as the Na, K-ATPase signal [9, 10].
How does ouabain cause cell death?
Ouabain-induced cell death was partially attenuated by the caspase inhibitor Z-VAD (100 μM). Consistently, the K+ ionophore valinomycin initiated apoptosis in LN229 cells in a K+ efflux-dependent manner. Ouabain caused an initial cell swell, which was followed by a sustained cell volume decrease.
What effect does ouabain have on the Na K pump?
What is the mechanism of action of ouabain?
Mechanism of Action Mechanism of Action information related to the record. Ouabain inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin).
How is ouabain used in the treatment of heart failure?
Pharmacology Pharmacology information related to this record. Ouabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.
Why does ouabain increase intracellular sodium and calcium?
Ouabain inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin).
How does ouabain affect the electrical activity of the heart?
Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Ouabain also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.