scholarly journals Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity

2015 ◽  
Vol 8 (4) ◽  
pp. 766-775 ◽  
Author(s):  
Jens Petter Bakkehaug ◽  
Anders Benjamin Kildal ◽  
Erik Torgersen Engstad ◽  
Neoma Boardman ◽  
Torvind Næsheim ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Atpase Activity ◽  
Myocardial Oxygen Consumption ◽  
Myosin Atpase ◽  
Cardiac Efficiency ◽  
Myosin Atpase Activity ◽  
Omecamtiv Mecarbil

Alterations in diaphragm contractility after nandrolone administration: an analysis of potential mechanisms

1999 ◽  
Vol 86 (3) ◽  
pp. 985-992 ◽  
Author(s):  
Michael I. Lewis ◽  
Mario Fournier ◽  
Amelia Y. Yeh ◽  
Paul E. Micevych ◽  
Gary C. Sieck
Keyword(s):  
Atpase Activity ◽  
Maximum Velocity ◽  
Interstitial Space ◽  
Myosin Atpase ◽  
Fiber Types ◽  
Intact Male ◽  
Cross Sectional ◽  
Myosin Atpase Activity ◽  
Relative Contribution

The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg ⋅ kg−1 ⋅ day−1; with weight gain, final dose: 2.7 mg ⋅ kg−1 ⋅ day−1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening ( V o) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as V o, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26–47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC2B with Nan. Ca2+-activated myosin ATPase activity was increased 35–39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of cross-bridge turnover and thus increased V o. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.

Methyl palmoxirate increases Ca2+-myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart

1985 ◽  
Vol 248 (5) ◽  
pp. E602-E606 ◽  
Author(s):  
W. H. Dillmann
Keyword(s):  
Atpase Activity ◽  
Cardiac Metabolism ◽  
Diabetic Rats ◽  
Myosin Atpase ◽  
Diabetic Rat ◽  
Glycolytic Flux ◽  
Acid Oxidation ◽  
Myosin Isoenzyme ◽  
Myosin Atpase Activity ◽  
Cardiac Ventricle

Previous studies have shown that in rats diabetes mellitus leads to a decrease in cardiac ventricle myosin V1 and an increase in myosin V3 levels. Insulin administration reverts myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on myosin isoenzyme distribution are a direct effect of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To gain further insight into this question diabetic rats received methyl palmoxirate, a potent inhibitor of long-chain fatty acid oxidation. Administration of 25 mg methyl palmoxirate X kg body wt-1 X day-1 to diabetic rats for 4 wk leads to a partial reversal of the effects of diabetes. Myosin V1 predominance is re-established and Ca2+-activated myosin ATPase activity increases by 60% (Ca2+-myosin ATPase normal rats 1.067 +/- 0.13 mumol Pi X mg protein-1 X min-1, diabetic rats 0.609 +/- 0.05 mumol Pi X mg protein-1 X min-1, diabetic + methyl palmoxirate rats 0.912 +/- 0.06 mumol Pi X mg protein-1 X min-1). The methyl palmoxirate-induced increase in myosin V1 levels and Ca2+-activated myosin ATPase activity occurred in the absence of changes in insulin and thyroid hormone levels. Methyl palmoxirate may have acted through its known inhibitory effect on cardiac beta-oxidation and/or the resultant stimulatory effect on glycolytic flux. Our findings may indicate that changes in cardiac substrate consumption can influence myosin isoenzyme predominance.

Regulation of Ca(2+)-dependent ATPase activity in detergent-skinned vascular smooth muscle

1994 ◽  
Vol 267 (3) ◽  
pp. H1032-H1039 ◽  
Author(s):  
Y. Zhang ◽  
R. S. Moreland
Keyword(s):  
Atpase Activity ◽  
Myosin Light Chain ◽  
Carotid Arteries ◽  
Myosin Atpase ◽  
Development Phase ◽  
Force Development ◽  
Myosin Atpase Activity ◽  
Force Maintenance ◽  
Triton X ◽  
Mlc Phosphorylation

We measured force, actin-activated myosin adenosinetriphosphatase (ATPase) activity, and myosin light-chain (MLC) phosphorylation levels in Triton X-100 detergent-skinned media of swine carotid arteries. Pseudo-ATPase activity composed of MLC kinase and phosphatase activities contributed maximally 12% to steady-state tissue ATPase activity. An increase in the Ca2+ concentration ([Ca2+]) induced an increase in force, MLC phosphorylation, and actin-activated myosin ATPase activity; this protocol was defined as the force development phase of contraction. Force maintenance was defined as the state induced by decreasing the [Ca2+] after a maximal contraction. Lowering the [Ca2+] decreased MLC phosphorylation to levels similar to those measured during force development at each [Ca2+]. In contrast, force remained at elevated levels while actin-activated myosin ATPase activity fell to significantly lower levels than those measured during the development phase for each [Ca2+]. We suggest that the significantly lower actin-activated myosin ATPase activity observed during a state of elevated force, compared with the development phase of a contraction, is evidence of slowly cycling latch bridges.

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