Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiomyopathic hamsters (UM-X7.1) show clinical signs of congestive heart failure and an abnormal EKG pattern. The sarcolemmal fraction obtained from the failing hearts at advanced stages of myopathy exhibited no change in the basal adenylate cyclase activity; however, the activity of this enzyme in the presence of catecholamines or NaF was lower in the failing heart sarcolemma than that in the control. The activities of Ca2+-ATPase, Mg2+-ATPase, and Na+-K+-ATPase in the failing heart sarcolemma were also less than the control values. These results suggest an association of membrane defect with heart failure.
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PMID:Membrane alteration in failing hearts of cardiomyopathic hamsters. 12 77

It is shown that the concentration of ouabain necessary for 50 per cent inhibition of the Na+K activated membrane ATPase of red cells is similar in man and horse. This is taken to indicate that the two species have similar sensitivity towards cardiac glycosides in general. In five adult healthy horses plasma digoxin concentration was measured with a radioimmunoassay technique after a single intravenous injection of 1 mg/100 kg body weight digoxin. The half time of elimination was 23 h and the apparent volume of distribution 7.3 litres/kg. An approximate estimate of plasma protein binding of digoxin was obtained by measuring digoxin with a fluorimetric assay in the ultrafiltrate from horse plasma containing 2-20 mug/ml. At concentrations below 10(-5)(g/ml 20 to 40 per cent of digoxin present in horse plasma is bound to protein. With this information and by using effective digoxin concentration measured in humans an average daily maintenance dose of 0-5-0-75 mg/100 kg body weight was calculated which may serve as a guideline in the treatment of congestive heart failure with digoxin in the horse.
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PMID:Pharmacological experiments as a basis for the administration of digoxin in the horse. 13 Jun 70

The Ca2+-activated myosin ATPase and the amino acid compositions of actin and myosin were determined for preparations from chronically failing dog hearts. Hypertrophy and congestive heart failure were produced by combined tricuspid valve insufficiency and pulmonary artery stenosis. Control, shamoperated, and noncardiac circulatory failure (inferior vena cava constriction) dogs also were studied. All hearts were divided into right ventricle, septum and left ventricle and each sample was individually analyzed. Calcium-activated ATPase decreased in the failing hearts and showed a distinct gradient of depression from right to left ventricles. There were no changes in ATPase activity among the other groups. The amino acid composition of actin was the same regardless of origin. The amino acid composition of myosin was unaltered except that cystine/2 residues were markedly decreased in failing heart myosin. The same gradient of depression was present as was found for Ca2+-activated myosin ATPase. This study suggests that protein metabolism is abnormal and that altered proteins are produced in hypertrophy and congestive heart failure. It appears that these changes do not affect all proteins, since actin was normal by the parameters studied. It is clear that the stressed ventricle is the most severely involved, but the entire heart is altered to some degree. Thus, we conclude that altered protein metabolism may be an important primary factor in the genesis of heart failure.
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PMID:The amino acid composition of actin and myosin and Ca2+-activated myosin adenosine triphosphatase in chronic canine congestive heart failure. 13 12

Myocardial hypertrophy in response to elevated myocardial wall stress largely results from myocyte hypertrophy. In congestive heart failure, this hypertrophy can have compensatory as well as critical relevance. On the one hand, it reduces myocardial wall stress in the case of hemodynamic overload by enhancing ventricular wall thickness. On the other hand, risks and problems may result from the tissue changes associated with myocardial "overload-hypertrophy", such as alterations in myocyte phenotype, augmentation of connective tissue in the myocardium, reductions in coronary reserve (even without altherosclerotic coronary stenoses), and alterations in the local formation of growth cofactors (i.e., enhanced myocardial expression of angiotensinogen and converting enzyme). Changes in myocyte phenotype occur in receptor signal transduction, in isoform shifts of contractile proteins and of key enzymes in energy metabolism towards a more fetal-like pattern, and in a "fragility" of Ca(++)-homeostasis (due to reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and enhanced expression of membrane Na+/Ca(++)-exchange in presence of maintained density of Ca(++)-channels). Additionally, the fraction of contractile fibers and mitochondria per myocyte cross-section can be reduced with attenuated systolic function. The fragility of Ca(++)-homeostasis must be regarded as potentially critical because of retarded inactivation of contraction and because of susceptibility to diastolic Ca(++)-overload with delayed after-depolarizations. Additionally, diastolic dysfunction may result from interstitial fibrosis and ischemia due to reduced coronary reserve (altered vascular structure and endothelial dysfunction).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The significance of myocardial hypertrophy in heart failure]. 129 Mar 5

Because the Na+ pump is considered to modulate the contractile force development by the cardiac muscle and depressed cardiac pump function is the hallmark of congestive heart failure, we characterized the sarcolemmal Na(+)-K(+)-ATPase activity in failing rat hearts after myocardial infarction. For this purpose, the left ventricular coronary artery was ligated, and hearts were examined 4, 8, and 16 wk later; sham-operated animals served as controls. Hemodynamic assessment revealed the presence of abnormal cardiac function at 4, 8, and 16 wk. Although accumulation of ascites in the abdominal cavity was present in experimental animals at 4 wk, other clinical signs of congestive heart failure in experimental rats including lung congestion and cardiac dilatation were evident 8 and 16 wk after induction of myocardial infarction. The depression in Na(+)-K(+)-ATPase activity in purified sarcolemmal membrane from the uninfarcted experimental left ventricle at 8 wk was associated with depressed Vmax without any changes in the affinities for Mg-ATP, Na+, and K+ or the pH optimum for the enzyme. The Kd values of both the high- and low-affinity binding sites for [3H]ouabain, which is believed to interact with Na(+)-K(+)-ATPase, were increased; however, no change in the density of either class of ouabain binding site was evident. The depression of Na(+)-K(+)-ATPase activity in failing hearts at 16 wk of myocardial infarction was not different from that observed at 8 wk but the enzyme activity was not altered at 4 wk of coronary occlusion. These data support the view that depression of Na(+)-K(+)-ATPase activity may serve as an adaptive mechanism during the development of congestive heart failure.
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PMID:Sarcolemmal Na(+)-K(+)-ATPase activity in congestive heart failure due to myocardial infarction. 131 80

To examine the status of sarcoplasmic reticulum (SR) with respect to Ca2+ transport in congestive heart failure due to myocardial infarction, the left coronary artery in rats was ligated for 4, 8, and 16 wk. The left heart function was assessed with an intraventricular pressure transducer, and SR membrane fractions from the right ventricle and the viable left ventricle were isolated for measuring the ATP-dependent Ca2+ uptake activities. In comparison to sham-operated controls, SR Ca2+ uptake activity was decreased in viable left ventricle of the experimental animals at 4, 8, and 16 wk. On the other hand, SR Ca2+ uptake activity in the right ventricle was increased at 4 and 8 wk, but no change was apparent at 16 wk of coronary occlusion. The decrease in SR Ca2+ uptake in left ventricle and increase in right ventricle were associated with corresponding changes in maximal velocity values without any alterations in the affinity for Ca2+. These opposite changes in the right and left ventricles were dependent on the scar size as well as time after inducing the myocardial infarction. The SR Ca(2+)-stimulated adenosinetriphosphatase activity was decreased in left ventricle and increased in the right ventricle from 4 wk experimental animals. The results suggest differential remodeling of the SR membranes with respect to Ca(2+)-pump mechanisms in left and right ventricles during the development of congestive heart failure.
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PMID:Differential changes in left and right ventricular SR calcium transport in congestive heart failure. 131 49

Because Na(+)-Ca2+ exchange and Ca2+ pump are thought to play a role in sarcolemmal Ca2+ movements, we examined the Na(+)-dependent Ca(2+)-uptake and ATP-dependent Ca(2+)-uptake activities in failing heart after myocardial infarction in rats. The left coronary artery was ligated, and the viable left ventricle was used 4, 8, and 16 wk later; sham-operated animals served as controls. Increased left ventricular diastolic pressure and decreased positive and negative change in pressure over time were observed in experimental animals at 4, 8, and 16 wk; these changes were associated with accumulation of fluid in the abdominal cavity. The sarcolemmal Na(+)-dependent Ca2+ uptake was depressed in 4-, 8-, and 16-wk experimental hearts. The decrease in sarcolemmal Na(+)-dependent Ca2+ uptake in failing hearts was seen when the activity was assayed either as a function of time or Ca2+ concentration; a depression of maximal velocity without any change in activity constant for Ca2+ was observed. No alteration in the Ca2+ pump (ATP-dependent Ca2+ accumulation and Ca(2+)-stimulated adenosinetriphosphatase) activities was evident in the 4-, 8-, and 16-wk experimental groups. These data suggest that changes in the Na(+)-dependent Ca2+ handling by the sarcolemmal membrane may be associated with contractile abnormalities in this model of congestive heart failure.
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PMID:Sarcolemmal calcium transport in congestive heart failure due to myocardial infarction in rats. 131 26

Na+,K(+)-ATPase is a major determinant of myocyte homeostasis and excitation-contraction. Cardiac glycosides such as digitalis and ouabain increase the inotropic state of the heart through the inhibition of Na+,K(+)-ATPase. While cardiac glycosides are commonly used in the setting of congestive heart failure, optimal therapy would depend upon an intact Na+,K(+)-ATPase system. Changes in Na+,K(+)-ATPase activity and glycoside receptor density with the development of cardiomyopathy have not been well defined. Accordingly, left ventricular (LV) function and Na+,K(+)-ATPase activity and glycoside binding were examined in 7 pigs with dilated cardiomyopathy and in 7 controls. Dilated cardiomyopathy was produced by pacing induced supraventricular tachycardia (SVT) for 3 weeks at 240 bpm. Left ventricular function was examined by simultaneous echocardiography and catheterization. Left ventricular fractional shortening significantly decreased with SVT (34 +/- 2 vs. 10 +/- 2%, P less than 0.05) and LV diastolic dimension and pressure significantly increased (3.8 +/- 0.3 vs. 5.1 +/- 0.4 cm, and 8 +/- 2 vs. 27 +/- 2 mmHg, respectively, P less than 0.05) as compared to controls. Na+,K(+)-ATPase activity was assayed as potassium dependent p-nitrophenol-phosphatase activity. Glycoside receptor density (Bmax) and affinity (KD) was determined using [3H]-ouabain binding assays. Na+,K(+)-ATPase activity, Bmax, and KD all significantly fell from control values with SVT induced cardiomyopathy (0.64 +/- 0.06 vs. 0.45 +/- 0.12 micrograms pNP/mg/h, 5.5 +/- 0.4 vs. 1.9 +/- 0.4 pmol/mg, and 15 +/- 3 vs. 9 +/- 3 nM, respectively, P less than 0.05). The distribution of Na+,K(+)-ATPase in LV sections taken from control and SVT hearts were examined using immunohistochemical techniques. A patchy distribution of Na+,K(+)-ATPase along the sarcolemma in SVT sections was observed as opposed to a more uniform distribution in control myocytes. There was no observable change in the relative content and distribution of the Na+,K(+)-ATPase isoforms alpha 2 and alpha 3 in the SVT sections as compared to controls. In an additional set of experiments, changes in LV as well as isolated myocyte responsiveness to ouabain were examined. Left ventricular fractional shortening and peak dP/dt were measured following administration of 20-60 micrograms/Kg of ouabain in control (n = 3) and SVT (n = 3) pigs. In the control group, 40 micrograms/Kg caused a 25% in LV fractional shortening and a 60% increase in peak dP/dt from baseline. Cumulative doses of 60 micrograms/Kg in the control pigs resulted in over a 75% increase in peak dP/dt from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myocardial Na+,K(+)-ATPase in tachycardia induced cardiomyopathy. 132 Jul 3

OPC-18790 [(+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]- 2(1H)-quinolinone], a novel positive inotropic agent, was investigated in several in vitro and in vivo experiments to elucidate its cardiovascular effects and its mechanism of action. In isolated blood-perfused dog heart preparations, OPC-18790 increased contractile force at 10 to 1,000 nmol i.a.; increased coronary arterial blood flow at 30 to 1,000 nmol; and decreased sinus rate slightly at 1,000 nmol. Atrio-ventricular nodal conduction was slightly facilitated with OPC-18790 (10 to 1,000 nmol), whereas ventricular automaticity tended to decrease. OPC-18790 (10(-6) to 10(-4) M) increased contractile force in isolated ventricular muscles of dogs, cats, rabbits and guinea pigs but not rats. OPC-18790 increased left ventricular contractile force dose-dependently in anesthetized open-chest dogs and in conscious dogs with slight or no changes in heart rate and blood pressure. The positive inotropic effect of OPC-18790 was not affected by beta-blockade. OPC-18790 (10(-5) to 10(-4) M) prolonged the duration of action potential in guinea pig papillary muscles. Na+, K(+)-ATPase was not inhibited, but peak-III phosphodiesterase (low Km cyclic AMP specific fraction, inhibited by cyclic GMP) was inhibited by OPC-18790 (IC50 = 0.41 x 10(-6) M) in dog myocardium. However, such an inhibitory action of phosphodiesterase can hardly be reconciled with the lack of a positive chronotropic effect shown by OPC-18790. Thus, these results suggest that OPC-18790 may have an additional mechanism. The cardiovascular effects revealed by this study suggest that OPC-18790 may exert a beneficial effect in the treatment of congestive heart failure.
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PMID:Cardiovascular actions of OPC-18790: a novel positive inotropic agent with little chronotropic action. 132 45

The beta adrenergic-modulated Na+/K+ ATPase pump rate of red blood cells was measured in vitro in 18 non diabetic obese patients. After challenge of erythrocytes with beta adrenergic selective agonist Salbutamol, the decrement of the K+ concentration in the suspending medium was assumed to be related to the Na+/K+ ATPase pump rate or to the number of beta 2 receptors. The mean K+ uptake was markedly increased in the erythrocytes of obese patients (1.58 mEq/l SD 0.18) if compared with 38 normal subjects (1.30 mEq/l SD 0.11) and with a population of 30 atopic patients that we have previously reported to have a reduced red cells beta 2 receptor activity (1.09 mEq/L SD 0.11). These results are not consistent with the hypothesis that a reduction in the Na+/K+ ATPase pump rate (at least in red blood cells) may be responsible for decreased metabolic rates leading to obesity. Since the autonomic nervous system is involved in the regulation of the cardiovascular system, it is conceivable that an increased Na+ ATPase pump rate (or supersensitivity) may be responsible of the increased incidence of hypertension, congestive heart failure and unexplained sudden death associated with obesity in some patients.
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PMID:Catecholamine-stimulated potassium transport in erythrocytes from normal and obese subjects. 133 39


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