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Choerospondias axillaris (Hog plum)
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Wild Plants, 2020
Aconitine was used to induce arrhythmia in the rats, ouabain was used to induce arrhythmia in guinea pigs, and arrhythmia was induced by ligation of coronary artery in the rats. C. axillaris extract significantly prolonged the lasting time of ventricular ectopic beats, ventricular tachycardia, ventricular fibrillation, and heart arrest induced by using aconitine in the rats. Similarly, the extract significantly prolonged the lasting time of arrhythmias induced by using ouabain in guinea pigs. The extract greatly reduced ectopic beats, delayed the beginning time of arrhythmias, shortened the persisting time of ventricular tachycardia, and decreased the frequency of ventricular fibrillation in the rats of ligation of coronary artery (Yang et al. 2008).
Genetic Basis of Blood Pressure and Hypertension
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Sandosh Padmanabhan, Alisha Aman, Anna F. Dominiczak
Ion transport by vascular smooth muscle cells may contribute to HTN-associated abnormalities of vascular tone and vascular growth, both of which are modulated by intracellular pH. An increased Na+/H+ exchanger (SLC9A1) can stimulate vascular tone and cell growth by increasing sodium reabsorption in renal proximal tubule cells (93). Other ion transporters considered are Na+ bicarbonate transporter (SLC4A10) and the Na+-Ca+ exchanger NCX (SLC8A1). One hypothesis for the mechanism by which excess salt intake elevates BP is through the observed rise in cardiotonic steroids such as ouabain in response to salt intake (94). It is believed that ouabain inhibits the plasma membrane Na+/K+ ATPase, leading to an increase in cytosolic Na+ concentration, which raises the cytosolic Ca2+ concentration through the involvement of the Na+/Ca2+ exchanger NCX (SLC8A1) and thereby increases contraction in vascular or heart muscle (95).
Endogenous Digitalis-Like Factors: Past Progress and Future Prospects
Published in Antonio Coca, Ricardo P. Garay, Ionic Transport in Hypertension: New Perspectives, 2019
Finally, in a related article by Harris et al.,49 the circulating endogenous levels of ouabain in humans are reported to be slightly greater than 100 fmol/ml of plasma. Comparison of this concentration to reports of the plasma concentration of ouabain required for a minimal biological effect clearly suggests a problem of potency. For example, Hougen and Smith50 have shown that the minimum plasma concentration of ouabain which will effect active cation transport in the heart is approximately 10 pmol/ml, i.e., 100-fold higher than the levels reported by Harris et al. Further review of the literature (see Reference 51 for an excellent discussion of the therapeutic levels of ouabain) indicate that even higher circulating levels of ouabain are needed to produce minimally measurable effects on Na, K-ATPase activity. Thus, it is difficult to believe that the ouabain apparently isolated and assayed by Mathews et al. could account for the effects on vascular Rb uptake seen in the work of Haddy et al.3,31 or the effects on lymphocyte Rb transport reported by Poston et al.,32,33 to cite but two examples. Indeed, this is the reason that both our laboratory15 and that of Godfraind52 have suggested and provided some evidence that the potency of an endogenous digitalis-like factor would be approximately 1000-fold greater than ouabain.
Role of TRPV1 channels on glycogen synthase kinase-3β and oxidative stress in ouabain-induced bipolar disease
Published in Journal of Receptors and Signal Transduction, 2022
Osman Kukula, Mustafa Nusret Çiçekli, Sinan Şafak, Caner Günaydın
In experimental models of psychiatric diseases, the method should exhibit face, construct, and predictive validity [6]. Mimicking the bipolar disease symptoms such as increased locomotion and depression is face valid. Pathophysiological aspects such as increased oxidative stress and dysregulated neurotransmission are considered to construct validity. Additionally, evaluating therapeutic agents used in treating the disorder, whether preventive or inhibitory in the disease state, is predictive validity. The model we used in this study is generally considered the only model that fulfills the mentioned three criteria for an adequate animal model of bipolar illness. Previous studies demonstrated that ouabain causes a manic-like state and significantly increases locomotion which persists until the tenth day of experiments [8,9]. Therefore, we selected the one-week treatment period to thoroughly evaluate the role of TRPV1 channels in mania and depression. Studies demonstrated that a decline in the Na+/K+-ATPase activity in acute manic episodes compared to recovered euthymic individuals [38]. Na+/K+-ATPase induces neuronal excitation, directly related to the increased locomotor activity in rats and manic episodes in bipolar patients [39]. In line with these studies, ouabain caused a significant increase in locomotor activity and anxiety-like behavior in our study.
Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: a new strategy to revisit mycobacterial targets and repurpose old drugs
Published in Expert Review of Anti-infective Therapy, 2020
Liliana Rodrigues, Pedro Cravo, Miguel Viveiros
Ouabain is a cardiac glycoside similar to digitoxin that is used to treat congestive heart failure, supraventricular arrhythmias and to control ventricular rate in the treatment of chronic atrial fibrillation [138,139]. This compound inhibits the Na+/K+-ATPase membrane transporter, causing an increase in intracellular sodium and calcium concentrations, which may promote activation of contractile proteins such as actin and myosin [140]. Ouabain has been demonstrated to potentiate the intracellular killing of M. tuberculosis by macrophages [141,142]. Recently, Kaur and collaborators performed a virtual screening to search for novel drugs against secretory lipid-catabolizing enzymes in M. tuberculosis. Ouabain was identified as a suitable drug for the enzyme LipU [143]. We have predicted a probable metal cation transporter P-type ATPase A (Rv1997) as a possible target for ouabain. These evidences suggest that this compound affects several cell processes and, thus, more studies are needed to clarify its mode of action.
Modulation of rat synaptosomal ATPases and acetylcholinesterase activities induced by chronic exposure to the static magnetic field
Published in International Journal of Radiation Biology, 2018
Marko Dinčić, Danijela Z. Krstić, Mirjana B. Čolović, Jelena Nešović Ostojić, Sanjin Kovačević, Silvio R. De Luka, Drago M. Djordjević, Saša Ćirković, Predrag Brkić, Jasna Todorović
The specific activity of total ATPase was determined in a standard reaction medium (200 μl), containing 50 mM Tris-HCl (pH 7.4), 100 mM NaCl, 20 mM KCl, 5 mM MgCl2, 2 mM ATP and 25 μl synaptosomal preparation. Assay for ecto-ATPase activity contained 50 mM Tris-HCl (pH 7.4), 5 mM MgCl2, 1 mM oubain, 2 mM ATP and 25 μl synaptosomal preparation. After preincubation for 10 min at 37 °C, the reaction was initiated by addition of ATP and stopped after 10 min by adding 22 μl ice cold of 3 M HClO4 and immediate cooling on ice. The concentration of liberated orthophosphate (Pi) from the hydrolysis of ATP was determined by modified spectrophotometric method (Vasic et al. 1999). The activity obtained in the presence of ouabain was attributed to ecto-ATPases activity. Na+/K+-ATPase activity was calculated by subtracting the ecto-ATPase activity from the total ATPase activity. The activities of Na+/K+-ATPase and ecto-ATPase were expressed as μmolPi/(h × mg protein).