scholarly journals Effects of a new cardiotonic agent 1,2-dihydro-6-methyl-2-oxo-5-(imidazo(1,2-a)pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (E-1020) on contractile force and cyclic AMP metabolism in canine ventricular muscle.

1990 ◽  
Vol 52 (2) ◽  
pp. 215-224 ◽  
Author(s):  
Hiroshi SATOH ◽  
Masao ENDOH
Keyword(s):  
Cyclic Amp ◽  
Contractile Force ◽  
Ventricular Muscle ◽  
Cardiotonic Agent ◽  
Hydrochloride Monohydrate

Abnormal contraction caused by expression of Gi-coupled receptor in transgenic model of dilated cardiomyopathy

2001 ◽  
Vol 280 (4) ◽  
pp. H1653-H1659 ◽  
Author(s):  
Anthony J. Baker ◽  
Charles H. Redfern ◽  
Mark D. Harwood ◽  
Paul C. Simpson ◽  
Bruce R. Conklin
Keyword(s):  
Transgenic Mice ◽  
Right Ventricular ◽  
Dilated Cardiomyopathy ◽  
Myocardial Function ◽  
Expression System ◽  
Contractile Force ◽  
Ventricular Muscle ◽  
Time To Peak ◽  
Contraction And Relaxation

Although increased Gi signaling has been associated with dilated cardiomyopathy in humans, its role is not clear. Our goal was to determine the effects of chronically increased Gi signaling on myocardial function. We studied transgenic mice that expressed a Gi-coupled receptor (Ro1) that was targeted to the heart and regulated by a tetracycline-controlled expression system. Ro1 expression for 8 wk resulted in abnormal contractions of right ventricular muscle strips in vitro. Ro1 expression reduced myocardial force by >60% (from 35 ± 3 to 13 ± 2 mN/mm2, P < 0.001). Nevertheless, sensitivity to extracellular Ca2+ was enhanced. The extracellular [Ca2+] resulting in half-maximal force was lower with Ro1 expression compared with control (0.41 ± 0.05 vs. 0.88 ± 0.05 mM, P < 0.001). Ro1 expression slowed both contraction and relaxation kinetics, increasing the twitch time to peak (143 ± 6 vs. 100 ± 4 ms in control, P < 0.001) and the time to half relaxation (124 ± 6 vs. 75 ± 6 ms in control, P < 0.001). Increased pacing frequency increased contractile force threefold in control myocardium ( P < 0.001) but caused no increase of force in Ro1-expressing myocardium. When stimulation was interrupted with rests, postrest force increased in control myocardium, but there was postrest decay of force in Ro1-expressing myocardium. These results suggest that defects in contractility mediated by Gi signaling may contribute to the development of dilated cardiomyopathy.

The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity to isoprenaline and papaverine in guinea-pig atria

1978 ◽  
Vol 48 (1) ◽  
pp. 107-116 ◽  
Author(s):  
Dietrich Reinhardt ◽  
Reinhard Butzheinen ◽  
Otto-Erich Brodde ◽  
Hans Joachim Schümann
Keyword(s):  
Cyclic Amp ◽  
Guinea Pig ◽  
Contractile Force ◽  
Temperature Dependent ◽  
Guinea Pig Atria

Cyclic AMP and the positive inotropic effect of norepinephrine and phenylephrine

1977 ◽  
Vol 55 (2) ◽  
pp. 279-287 ◽  
Author(s):  
T. T. Martinez ◽  
J. H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Cell Membrane ◽  
Time Course ◽  
Positive Inotropic Effect ◽  
Contractile Response ◽  
Contractile Force ◽  
Time Response ◽  
Inotropic Effect ◽  
Chronotropic Response ◽  
Right Atria

Time-response studies of the effects of norepinephrine and phenylephrine revealed that both agonists caused an increase in cyclic AMP levels before increases in contractile force in either the electrically stimulated left atria or spontaneously beating right atria of the rat. Norepinephrine caused a nearly sixfold increase in cyclic AMP, whereas phenylephrine produced only a 50% increase in the nucleotide. Pretreatment with reserpine did not affect the norepinephrine cyclic AMP response; however, the phenylephrine cyclic AMP response was abolished. Reserpine pretreatment did not significantly affect the contractile responses of either amine. In the presence of propranolol, norepinephrine was found to have the ability to produce an increase in contractile force in which cyclic AMP was apparently not involved. The time course of the contractile response induced by adrenergic amines was found to be remarkably influenced by the chronotropic response in spontaneously beating preparations while the cyclic AMP response was not greatly affected. This difference in the contractile response may be due to the ability of the chronotropic response to influence the flux of calcium through the cell membrane.

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