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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The energy output of a cardiac contraction can be divided into several phenomenologically measured components, although it must be emphasized that such subdivisions are often thermodynamically misleading. There is an activation term that relates to Ca++ release and retrieval, a work term and a stress or load-dependent heat term. The work and load-dependent energy terms presumably have their origin in the actin-activated myosin ATPase. It can be shown that the enthalpy: load relationship has a similar format across both mammalian and amphibian hearts: the scaling of both the energy and load axes is however altered by changes in contractility. The fact that enthalpy production is so clearly load-dependent indicates that there is a Fenn effect in cardiac muscle, although the discovery that energy output is greatest in an isometric contraction clearly contradicts one of the two central findings of Fenn's skeletal muscle investigations. Cardiac oxygen consumption per beat can be linearly correlated with ventricular systolic pressure--volume area (PVA) which is defined in terms of stroke work and potential energy components. If the basal and activation components are subtracted out cardiac muscle can be shown to operate at a constant PVA efficiency. The existing myothermic and polarographic data can be reconciled with the PVA concept.
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PMID:Cardiac energetics and the Fenn effect. 295 66

We have previously shown that swim conditioning corrects the depressed mechanical function and myosin adenosinetriphosphatase (ATPase) activities associated with renovascular hypertension (HTN) in the rat. The present study was designed to assess the effects of swim conditioning on another form of systolic overload, subdiaphragmatic suprarenal aortic stenosis. Cardiac mechanics in an isolated working heart apparatus and myosin enzymology were studied in four groups of rats: controls (C), animals with chronic systolic overload secondary to aortic constriction (St), swim-conditioning animals (Sw), and animals exposed to a combined load (St-Sw). Heart weight was increased by 23% in St, 27% in Sw, and 36% in St-Sw. In contrast to HTN, cardiac pump and muscle function were not depressed in St. Sw was associated with improved cardiac output, stroke work, and velocity of circumferential fiber shortening. St-Sw showed improved mechanical cardiac performance relative to both C and St. The percent of ventricular myosin of the V1 type and Ca2+-activated myosin ATPase activity relative to C was unchanged in Sw but was depressed in St and St-Sw. These data demonstrate that the salutory mechanical effects of Sw can be superimposed on the systolic overload of St. However, the dissociation between mechanics and myosin enzymology suggests that factors in excitation-contraction coupling other than myosin isoenzyme shifts are responsible for this finding.
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PMID:Effects of systolic overload and swim training on cardiac mechanics and biochemistry in rats. 296 13

The goal was to describe the metabolic profile of ganglionic and cortical arteries and arterioles in aging normotensive male rats. Five enzymes indicative of key metabolic pathways in the vessel walls were semiquantitatively evaluated using bright-field histochemical microscopy. Lactate dehydrogenase showed significant reactivity which increased with vessel diameter in cortical and ganglionic vessels in all age groups tested. Succinate dehydrogenase and cytochrome oxidase showed little reactivity in both cortical and ganglionic vessels, suggesting a reduced role for aerobic metabolic pathways. Myosin ATPase reactivity was high in cortical and ganglionic vessels. Only this enzyme showed an increased reactivity that was correlated with the age and diameter of the vessel. Glucose-6-phosphate dehydrogenase reactivity was more pronounced in cortical than ganglionic vessels, suggesting that the hexose-monophosphate-shunt may be more active in the cortical vessels. There were no regional differences in enzyme reactivity throughout the caudatoputamen. In conclusion, both the cortical and ganglionic vessels are metabolically active, with significant anaerobic glycolysis, and reduced, but observable capacity for aerobic metabolism. The decreased myosin ATPase reactivity and the low level of glucose-6-phosphate dehydrogenase reactivity in the ganglionic arterioles of senescent rats may contribute to the susceptibility of these vessels to cerebrovascular accidents.
Stroke
PMID:A histochemical study of cerebral cortical vessels and ganglionic vessels of the caudatoputamen in aging normotensive rats. 315 35

To explore the interactions of physiologic and pathologic hypertrophy, four groups of hearts were studied in an isolated working rat heart apparatus. Cardiac contractile proteins were also evaluated. The groups were hearts of female control sedentary rats; rats subjected to a 10-week swimming programme; rats with renal hypertension; and hypertensive rats subjected to a 10-week swimming programme. The swimming programme in normotensive female rats caused a 30% cardiac hypertrophy, in hypertensive animals 46% hypertrophy, and in combined hypertension and swimming 70% hypertrophy. Ca2+-myosin ATPase activity and actin-activated myosin ATPase were elevated in hearts of swimmers, depressed in hearts of hypertensive sedentary animals and similar to control values in hearts of hypertensive swimmers. Myosin V1 isoenzyme content was increased in hearts of swimmers, depressed in hearts of hypertensives, but normal in hearts of hypertensive swimmers. Reciprocal relationships were seen with the V3 isoenzyme. Stroke work, mean velocity of circumferential fibre shortening, and per cent fractional shortening at the midwall showed increased values for hearts of swimmers, depressed values for hearts of hypertensives, and normal values or values above the control for hearts of hypertensive swimmers. Myocardial flow measured with microspheres was increased in the left ventricle of swimmers, depressed in hearts of hypertensives and still depressed in hypertensive swimmers, but significantly higher than in the hypertensives alone. The correlation of actin-activated ATPase activity and of fractional shortening was linear among the four groups. These studies demonstrate that physiologic and pathologic hypertrophy in the rat have distinctly opposite effects on contractile proteins and contractile performance. When one type of hypertrophy is superimposed on the other the effects are additive.
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PMID:Correlation of myosin isoenzyme alterations with myocardial function in physiologic and pathologic hypertrophy. 624 4

We performed a chronologic investigation of left (LV) and right (RV) ventricular myosin ATPase activity and hemodynamics in newborn lambs. We found an elevation in myosin ATPase activity for the LV, which was achieved by 6 to 8 weeks of age and which correlated directly with increasing ventricular stroke work. Myosin ATPase activity did not increase with age for the RV, a finding which was associated with a postnatal decrease in ventricular stroke work. These findings may represent an important postnatal adaptation of newborn myocardium to the demands of extrauterine life.
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PMID:Maturational changes in cardiac muscle myosin adenosine triphosphatase activity relative to hemodynamic alterations in newborn lambs. 646 50

In an attempt to elucidate the effects of two major risk factors of heart failure in humans, high blood pressure and coronary artery disease, renal hypertension and coronary artery constriction were induced singularly and in combination in rats, and the functional, structural, and biochemical alterations of the myocardium were examined 12-13 wk later. Renal hypertension (RH), coronary narrowing (CN), and their association (NH) resulted in left ventricular failure demonstrated by a significant increase in left ventricular end-diastolic pressure, a decrease in +dP/dt and -dP/dt, and a reduction in stroke volume and cardiac output. Measurements of ventricular loading documented that RH was characterized by elevations in systolic and diastolic wall stress of 42 and 160%, respectively. Corresponding changes with NH were 80 and 315%. CN was accompanied by an augmentation of diastolic wall stress only (280%). The abnormalities in mural stress were coupled with reductions in systolic and diastolic wall thickness-to-chamber radius ratios of 39 and 29% after CN. These anatomic parameters were preserved with RH, whereas the systolic wall thickness-to-chamber radius ratio was reduced 31% with NH. Structurally, multiple foci of replacement fibrosis were found with each intervention. The sites of tissue injury and their volume percent in the myocardium were comparable with CN and RH but were significantly more numerous and occupied a larger fraction of the ventricular wall in the presence of NH. Biochemically, the calcium dose-response curve of myofibrillar Mg2+ adenosinetriphosphatase (ATPase) activity did not vary with CN, RH, and NH. In contrast, a marked decrease in Ca2+ myosin ATPase activity was found in NH rats in association with a shift in myosin isoenzymes from V1 to V3. In conclusion, multiple physiological, morphological, and biochemical factors may participate in the generation of the abnormalities in ventricular loading with hypertension and/or coronary artery stenosis.
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PMID:Effects of hypertension and coronary constriction on cardiac function, morphology, and contractile proteins in rats. 836 72

The myosin motor protein generates force in muscle by hydrolyzing Adenosine 5'-triphosphate (ATP) while interacting transiently with actin. Structural evidence suggests the myosin globular head (subfragment 1 or S1) is articulated with semi-rigid catalytic and lever-arm domains joined by a flexible converter domain. According to the prevailing hypothesis for energy transduction, ATP binding and hydrolysis in the catalytic domain drives the relative movement of the lever arm. Actin binding and reversal of the lever-arm movement (power stroke) applies force to actin. These domains interface at the reactive lysine, Lys84, where trinitrophenylation (TNP-Lys84-S1) was observed in this work to block actin activation of myosin ATPase and in vitro sliding of actin over myosin. TNP-Lys84-S1's properties and interactions with actin were examined to determine how trinitrophenylation causes these effects. Weak and strong actin binding, the rate of mantADP release from actomyosin, and actomyosin dissociation by ATP were equivalent in TNP-Lys84-S1 and native S1. Molecular dynamics calculations indicate that lever-arm movement inhibition during ATP hydrolysis and the power stroke is caused by steric clashes between TNP and the converter or lever-arm domains. Together these findings suggest that TNP uncouples actin activation of myosin ATPase and the power stroke from other steps in the contraction cycle by inhibiting the converter and lever-arm domain movements.
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PMID:Chemical decoupling of ATPase activation and force production from the contractile cycle in myosin by steric hindrance of lever-arm movement. 1254 86

Cardiac troponin C is the Ca2+-dependent switch for heart muscle contraction. Troponin C is associated with various other proteins including troponin I and troponin T. The interaction between the subunits within the troponin complex is of critical importance in understanding contractility. Following a Ca2+ signal to begin contraction, the inhibitory region of troponin I comprising residues Thr128-Arg147 relocates from its binding surface on actin to troponin C, triggering movement of troponin-tropomyosin within the thin filament and thereby freeing actin-binding site(s) for interactions with the myosin ATPase of the thick filament to generate the power stroke. The structure of calcium-saturated cardiac troponin C (C-domain) in complex with the inhibitory region of troponin I was determined using multinuclear and multidimensional nuclear magnetic resonance spectroscopy. The structure of this complex reveals that the inhibitory region adopts a helical conformation spanning residues Leu134-Lys139, with a novel orientation between the E- and H-helices of troponin C, which is largely stabilized by electrostatic interactions. By using isotope labeling, we have studied the dynamics of the protein and peptide in the binary complex. The structure of this inhibited complex provides a framework for understanding into interactions within the troponin complex upon heart contraction.
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PMID:Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I. 1273 41

Muscle contraction is driven by a cycle of conformational changes in the myosin II head. After myosin binds ATP and releases from the actin fibril, myosin prepares for the next power stroke by rotating back the converter domain that carries the lever arm by 60 degrees . This recovery stroke is coupled to the activation of myosin ATPase by a mechanism that is essential for an efficient motor cycle. The mechanics of this coupling have been proposed to occur via two distinct and successive motions of the two helices that hold the converter domain: in a first phase a seesaw motion of the relay helix, followed by a piston-like motion of the SH1 helix in a second phase. To test this model, we have determined the principal motions of these structural elements during equilibrium molecular dynamics simulations of the crystallographic end states of the recovery-stroke by using principal component analysis. This reveals that the only principal motions of these two helices that make a large-amplitude contribution towards the conformational change of the recovery stroke are indeed the predicted seesaw and piston motions. Moreover, the results demonstrate that the seesaw motion of the relay helix dominates in the dynamics of the pre-recovery stroke structure, but not in the dynamics of the post-recovery stroke structure, and vice versa for the piston motion of the SH1 helix. This is consistent with the order of the proposed two-phase model for the coupling mechanism of the recovery stroke. Molecular movies of these principal motions are available at http://www.iwr.uni-heidelberg.de/groups/biocomp/fischer.
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PMID:The principal motions involved in the coupling mechanism of the recovery stroke of the myosin motor. 1727 22


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