Effect of anti-digoxin antiserum on endoxin and membrane ATPase activity in hypoxia-reoxygenation induced myocardial injury.
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AIM: To evaluate the protective effect of anti-digoxin antiserum on hypoxia-reoxygenation induced injured myocardium and its mechanism. METHODS: Anti-digoxin antiserum of different concentrations was used, its effect on endoxin and ATPase activity in cell membrane in hypoxia-reoxygenation myocardium model was observed. RESULTS: The level of endoxin was remarkably higher, ATPase activities in cell membrane were remarkably lower in hypoxic group and hypoxia-reoxygenation injury group than those of normal group; anti-digoxin antiserum could resume ATPase activity in a concentration-dependent manner. CONCLUSION: Rise of endoxin was the molecular biological basis of myocardial damage during myocardial hypoxia-reoxygenation. Anti-digoxin antiserum had lessened myocardial injury and had a protective effect on hypoxia-reoxygenation myocardium by antagonizing effect of endoxin. (+info)
Role of catecholamines in the central mechanism of emetic response induced by peruvoside and ouabain in cats.
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1 Peruvoside, (a glycoside obtained from the plant, Thevetia neriifolia Juss) and ouabain produce emesis in cats. Vomiting is not produced by these drugs in animals pretreated with catecholamine depleting drugs like reserpine, tetrabenazine or syrosingopine. Chloropromazine hydrochloride, mepyramine maleate, or BOL-148 administered intravenously or intracerebro-ventricularly do not afford protection.2 Phenoxybenzamine produces partial protection against peruvoside-induced emesis.3 Haloperidol (1 mg/kg i.v.) prevents vomiting induced by peruvoside or ouabain. Intracerebroventricularly administered haloperidol is ineffective.4 Cats pretreated with SKF-525-A, are not protected by haloperidol. Animals pretreated with phenobarbitone in a dose of 25 mg/kg for a week were protected by haloperidol, 250 mug/kg i.e. one quarter of the effective antiemetic dose in normal cats.5 It is postulated that catecholamines are involved in the mechanism of vomiting induced by cardiac gycosides. Further, a metabolite of haloperidol seems to be responsible for its effective antiemetic action. (+info)
Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension.
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An ouabain-like factor has been implicated repeatedly in salt-sensitive hypertension as a natriuretic agent. However, the response of plasma ouabain-like factor to acute and chronic variation of body sodium is unclear. We studied 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blind randomized crossover design involving chronically controlled sodium intake and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels of ouabain-like factor were higher during sodium depletion (acute: 338.8+/-17.4 and 402.7+/-22.8 pmol/L for baseline and low sodium, respectively, P<0.01; chronic: 320.4+/-32.0 versus 481.0+/-48.1 pmol/L, P=0.01). No significant change in plasma ouabain-like factor was observed after a 2-hour saline infusion (333.4+/-23.9 pmol/L) or controlled sodium (402.1+/-34.9 pmol/L). When patients were divided into salt-sensitive or salt-resistant groups, no differences in plasma ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocols: salt resistant (n=69, 340.1+/-25.9 pmol/L) versus salt sensitive (n=69, 337.4+/-23.6 pmol/L) and chronic salt resistant (n=11, 336.0+/-53.2) versus salt sensitive (n=9, 301.1+/-331.4 pmol/L). However, circulating ouabain-like factor was increased by sodium depletion in both groups. These results demonstrate that circulating ouabain-like factor is raised specifically by maneuvers that promote the loss of body sodium. Acute expansion of body fluids with isotonic saline is not a stimulus to plasma ouabain-like factor. Moreover, basal levels of plasma ouabain-like factor do not differ among patients with salt-sensitive or salt-resistant hypertension. Taken together, these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone. (+info)
Endoxin:a major factor regulating cardiovascular system.
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Endoxin is a factor with a digitalis-like biological activity. It is a Na+ pump inhibitor and may be an endogenous medium of digitalis receptor. There are abnormal plasma levels of endoxin in some pathophysiologic states such as hypertension, acute myocardial infarction, arrhythmia, heart failure, etc. Some studies have demonstrated that the abnormal endoxin levels may be implicated in pathogenesis of these diseases or pathophysiologic process involved. Therefore, to clarify the effects of endoxin has much significance in understanding pathogenesis, prevention and treatment of hypertension and other cardiovascular diseases. (+info)
Activation of cardiac ryanodine receptors by cardiac glycosides.
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This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 channel activity. Digoxin and actodigin increased single-channel activity at low concentrations normally associated with therapeutic plasma levels, yielding a 50% of maximal effect of approximately 0.2 nM for each agent. Channel activation by glycosides did not require MgATP and occurred only when digoxin was applied to the cytoplasmic side of the channel. Similar results were obtained in human RyR2 channels; however, neither the crude skeletal nor the purified cardiac channel was activated by glycosides. Channel activation was dependent on [Ca2+] on the luminal side of the bilayer with maximal stimulation occurring between 0.3 and 10 mM. Rat RyR2 channels were activated by digoxin only at 1 microM, consistent with the lower sensitivity to glycosides in rat heart. These results suggest a model in which RyR2 channel activation by digoxin occurs only when luminal [Ca2+] was increased above 300 microM (in the physiological range). Consequently, increasing SR load (by Na+ pump inhibition) serves to amplify SR release by promoting direct RyR2 channel activation via a luminal Ca2+-sensitive mechanism. This high-affinity effect of glycosides could contribute to increased SR Ca2+ release and might play a role in the inotropic and/or toxic actions of glycosides in vivo. (+info)
Endogenous ligand of alpha(1) sodium pump, marinobufagenin, is a novel mediator of sodium chloride--dependent hypertension.
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BACKGROUND: Digitalis-like sodium pump ligands (SPLs) effect natriuresis via inhibition of renal tubular Na(+),K(+)-ATPase but may induce vasoconstriction. The present study investigated the potential roles of 2 putative endogenous SPLs, an ouabain-like compound (OLC) and an alpha(1) Na(+),K(+)-ATPase inhibitor, marinobufagenin (MBG), in regulating natriuresis and blood pressure (BP) responses to sustained and acute NaCl loading in Dahl salt-sensitive rats (DS). METHODS AND RESULTS: During 4 weeks of an 8% NaCl diet, DS exhibited a progressive increase in MBG renal excretion (66 +/-13 pmol/24 hours at week 4 versus 11 +/- 1 pmol/24 hours at baseline, n=48), which paralleled an increase in systolic BP (174 +/- 10 mm Hg at week 4 versus 110 +/- 2 mm Hg at baseline). By contrast, OLC excretion peaked at week 1 and returned to baseline levels. Administration of an anti-MBG, but not anti-ouabain antibody, to DS after 3 weeks of a high NaCl diet lowered BP (139 +/- 7 versus 175 +/- 5 mm Hg, P<0.001, n=5). Acute NaCl loading (2 hours) of DS (n=5) increased MBG and OLC excretion and natriuresis. Pretreatment of acutely NaCl-loaded DS with an anti-MBG antibody (n=5) reduced the excretion of sodium and MBG but not that of OLC. An anti-ouabain antibody (n=5) reduced sodium excretion and both OLC and MBG. CONCLUSIONS: An initial transient stimulation of OLC induced by NaCl loading of DS precedes an MBG response. A sustained increase in MBG production in DS contributes to the chronic BP elevation induced by a sustained high NaCl intake. (+info)
Systolic time intervals in constrictive pericarditis. A study before and after digitalis.
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Systolic time intervals were studied in 9 patients with documented constrictive pericarditis before and 15 to 20 minutes after intravenous administration of peruvoside (a quick acting digitalis-like glycoside) to determine underlying myocardial dysfunction. Data were compared with those of similarly studied normal subjects and patients with known myocardial dysfunction. Left ventricular ejection time index (LVETI) decreased in normal subjects (P less than 0.01) and in most patients with constrictive pericarditis, and increased marginally in those with myocardial dysfunction (NS) after peruvoside administration. Pre-ejection period index (PEPI) shortened significantly (P less than 0.01) after peruvoside in normal subjects and in patients with myocardial failure, but not in constrictive pericarditis. Likewise the predicted ejection fraction was insignificantly altered in constrictive pericarditis but significantly so (P less than 0.01) in myocardial failure and normal subjects. The response of one patient with constrictive pericarditis to parenteral peruvoside administration was similar to that seen in patients with myocardial failure. This patient had a delayed recovery after pericardiectomy. PEPI/LVETI ratio and ejection fraction were also abnormal in other patients with constrictive pericarditis when compared to normal subjects. Such abnormalities and the unusual response of some patients to administration of peruvoside may reflect underlying myocardial dysfunction in patients with constrictive pericarditis. However, it is possible that the rigid pericardium also contributes to these abnormalities to a varying extent. Systolic time indices and their response to digitalis appear to be a useful, atraumatic method for detecting underlying myocardial dysfunction in patients with constrictive pericarditis. (+info)
Simultaneous determination of cardenolides by sonic spray ionization liquid chromatography-ion trap mass spectrometry--a fatal case of oleander poisoning.
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Simultaneous determination of oleandrin and its three related compounds, desacetyloleandrin, oleandrigenin, and gitoxigenin in blood by using liquid chromatography-three-dimensional quadrupole mass spectrometry (LC-3DQMS) system equipped with sonic spray ionization (SSI) interface was conducted. This analyzing method was suitable for all of these compounds except gitoxigenin. The limits of detection of oleandrigenin and desacetyloleandrin from blood were 2 ng/mL and that of oleandrin was 3 ng/mL. The calibration curves for oleandrin, desacetyloleandrin, and oleandrigenin were linear in the range of 5-100 ng/mL. The coefficients of variation of oleandrin, desacetyloleandrin, and oleandrigenin in the blood were satisfactory ranging from 1.6% to 4.1%. This analysis method was applied to a fatal case of oleander poisoning. As a result of liquid chromatography-mass spectrometry (LC-MS) analysis, oleandrin was detected in heart blood and cerebrospinal fluid. Desacetyloleandrin, oleandrigenin, and gitoxigenin were not detected. In order to make identification of oleandrin reliable, LC-MS-MS analysis was performed. The concentrations of oleandrin found in the heart blood and cerebrospinal fluid were 9.8 and 10.1 ng/mL, respectively. (+info)