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)

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.
Stroke 1989 Sep
PMID:Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats. 247 24

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28-29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70-80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as "chronotropic incompetence") found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac adaptations to endurance training in rats with a chronic myocardial infarction. 252 73

Smooth muscle relaxation due to activation of Na+-K+-adenosinetriphosphatase (ATPase) (K+ relaxation) was studied in isolated tail arteries from stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats. Exposure to K+ (7 mM) relaxed a norepinephrine (1 microM) contraction induced in K+-free physiological salt solution (PSS) by 46 +/- 3% in WKY and by 81 +/- 3% in SHRSP. Incubation with monensin (10 microM) augmented the K+-relaxation in WKY to 61 +/- 5%. Incubation with amiloride (10 microM) or with low-Na+ (10 mM) PSS attenuated the K+ relaxation in SHRSP to 34 +/- 3 and 5 +/- 2%, respectively. Incubation with high-Ca2+ (6.6 mM) PSS attenuated the K+ relaxation in WKY to 25 +/- 3% but resulted in only a slight decrease in the relaxation in SHRSP (to 73 +/- 2%). We conclude 1) that a greater Na+ leakiness of the plasma membrane in SHRSP than in WKY while the Na+ pump is inactive in K+-free PSS can explain the greater relaxation observed when the Na+ pump is reactivated and 2) that the Na+ leakiness of the membrane is more attenuated by Ca2+ in the WKY than in the SHRSP. We hypothesize that this Ca2+ effect reflects a normally large amount of this ion that can be bound to and thereby stabilize the membrane of the WKY, decreasing its permeability to Na+. The membrane of the SHRSP is deficient in its Ca2+-binding sites. Hence the added Ca2+ does not further stabilize its membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potassium-induced relaxation of arteries in hypertension: modulation by extracellular calcium. 253 82

The capability of cyclohexylphenol exaprolol of protecting the ischaemic myocardium during ischaemic cardiac arrest was assessed in the isolated working rat heart. Exaprolol added to the perfusion medium in a dose of 10(-7) mol.l-1 only minimally influenced the left ventricular function (reduced the stroke volume by 18.84% and cardiac output by 14.63%). The hearts were subjected to global ischaemia for 75 min at 26 degrees C and subsequently reperfused for 60 min at 37 degrees C. The recovery of left ventricular function following reperfusion, expressed as a percentage of preischaemic functional performance was used as an indicator of the ischaemic tolerance of the heart. The effect of exaprolol on sarcolemmal (Na+ + K+)-, Mg2+- and Ca2+-ATPase activities was also examined. Exaprolol-pretreated hearts revealed better postischaemic recovery of the left ventricular dP/dt max and stroke volume as well as improved efficiency in the transformation of chemical energy to mechanical work. Exaprolol in 10(-4) mol.l-1 concentration significantly stimulated the specific activity of sarcolemmal (Na+ + K+)-ATPase. Possible mechanisms of the salutary effect of exaprolol on the ischaemic heart are discussed.
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PMID:The influence of exaprolol upon the ischaemic rat heart and its interaction with sarcolemmal (Na+ + K+)-ATPase. 256 82

The Na,K-adenosine triphosphatase (ATPase) alpha 2 subunit gene was found to display restriction fragment length polymorphisms (RFLPs) between the genomes of normotensive and hypertensive rats when digested with the restriction enzymes Bgl II and Hind III. In normotensive rats, we tested the spontaneously hypertensive rat (SHR) and its substrain, the stroke-prone spontaneously hypertensive rat (SHR-SP). Rat (SD) complementary (c) DNA encoding the alpha 2 subunit of Na,K-ATPase was used as a probe. When the probe was dissected these RFLPs were found to occur in the vicinity of the genomic locus encoding the middle part of the messenger (m) RNA for the alpha 2 subunit of Na,K-ATPase. A Northern blot analysis indicated that these RFLPs did not influence the alpha 2 subunit with regard to either size or amount of mRNA.
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PMID:The Na,K-ATPase alpha 2 subunit gene displays restriction fragment length polymorphisms between the genomes of normotensive and hypertensive rats. 257 29

Swelling of astrocytes in the brain is a major cause of the morbidity and mortality associated with stroke and head trauma. Using a human astrocytoma cell line (UC-11MG) as a model system, we studied cell volume changes caused by ATP depletion under conditions mimicking hypoxia. ATP levels were reduced to less than 10% of control using the metabolic inhibitors KCN or antimycin in combination with glucose deprivation. This was sufficient to eliminate ouabain-sensitive 86Rb+ uptake, indicating the Na+-K+-adenosinetriphosphatase was not operating. Furosemide-sensitive 86Rb+ uptake was reduced by approximately 60%, indicating Na+-K+-2Cl- cotransport was also sensitive to ATP loss. ATP depletion resulted in a 30-40% reduction of cell volume within 60 min. ATP depletion also resulted in a net loss of intracellular K+. This loss of K+ could be blocked by Ba2+, indicating the K+ loss was through a conductive channel. When the net K+ loss was blocked by Ba2+, the volume decrease was also prevented. The cells remained viable throughout the time period as judged by exclusion of ethidium bromide by 99% of the cells and recovery of ATP levels to 75% of control within 60 min. We conclude that ATP depletion, following inhibition of glycolysis and oxidative phosphorylation, causes astrocytes to shrink because of a more rapid loss of K+ than uptake of Na+. Thus it appears that ATP depletion alone is not sufficient to account for the rapid phase of astrocytic swelling observed during cerebral ischemia.
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PMID:Energy-dependent cell volume maintenance in UC-11MG human astrocytomas. 280 31

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.
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PMID:Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats. 284 Feb 35

In Quin-2-loaded erythrocytes of two genetically hypertensive rat strains (spontaneously hypertensive rats, SHR, and the Milan hypertensive strain, MHS) intracellular Ca2+ (Ca2+i) concentration and 45Ca influx rate were increased by 25-30 and 15-20% respectively, in comparison with normotensive controls (Wistar-Kyoto rats, WKY, and rats of the Milan normotensive strain, MNS). After 4 h incubation in the presence of 5 mmol/l sodium vanadate (Na3VO4) as an inhibitor of Ca-ATPase, 45Ca content of intact erythrocytes of SHR was twofold higher while erythrocyte count of stroke-prone SHR (SHRSP) was threefold higher than in WKY. This increase was observed in SHR during the pre-hypertensive stage. Under the same conditions, no difference was noted between MHS and MNS rats. The rate of 32P influx, as well as the concentration of exchangeable chloride, was studied. We failed to detect any significant differences in either parameter between hypertensive and normotensive rats, suggesting that altered cell membrane potential was not responsible for allied Ca fluxes. Erythrocyte shrinking, however, resulted in a two to threefold increase in the rate of 45Ca influx. Neither the rate of 45Ca influx nor Ca2+i were modified by the inhibitor of calmodulin-dependent reactions, R24571 (10 mumol/l). It is suggested that the higher rate of Ca2+ influx in Quin-2-loaded erythrocytes of SHR, as well as the increment in 45Ca content in intact erythrocytes treated with orthovanadate, is due to a change in membrane skeleton organization and cell shrinkage.
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PMID:Calcium transport in erythrocytes of rats with spontaneous hypertension. 284 88

Development of heat stroke led to a decrease in main reactions of energy production and energy potential in erythrocytes, to a decrease in activity of Na+, K+-ATPase and in content of sodium and potassium as well as to alterations in forms and to decrease in volume of these cells.
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PMID:[Relation between energy metabolism, Na+ and K+ levels, and Na,K-ATPase activity in erythrocytes and their volume and shape during overheating]. 285 Dec 13

Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) were subjected to swimming training 6 times/wk, commencing at 4 wk of age, to determine whether this type of endurance exercise might alter contractile proteins and cardiac function in young adult SHR. The total duration of exercise was 190 h. Myofibrillar adenosinetriphosphatase (ATPase) activity was assayed at various free [Ca2+] ranging from 10(-7) to 10(-5) M. Ca2+-stimulated ATPase activity of actomyosin and purified myosin was determined at various Ca2+ concentrations both in the low and high ionic strength buffers. Actin-activated myosin ATPase activity of purified myosin was assayed at several concentrations of actin purified from rabbit skeletal muscle. Under all these conditions the contractile protein ATPase activity was comparable between trained and untrained WKY and SHR. Analysis of myosin isoenzymes on pyrophosphate gels showed a single band corresponding to V1 isoenzyme, and there were no differences between swimming-trained and nontrained WKY and SHR. Ventricular performance was assessed by measuring cardiac output and stroke volume after rapid intravenous volume overloading. Both cardiac index and stroke index were comparable in nontrained WKY and SHR but were significantly increased in the trained groups compared with their respective nontrained controls. These results suggest that myosin ATPase activity and distribution of myosin isoenzymes are not altered in the moderately hypertrophied left ventricle whether the hypertrophy is due to genetic hypertension (SHR) or to exercise training (trained WKY). Moreover, the data indicate that SHR, despite the persistence of a pressure overload, undergo similar increases in left ventricular mass and peak cardiac index after training, as do normotensive WKY.
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PMID:Effect of swimming training on cardiac function and myosin ATPase activity in SHR. 293 19


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