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.

The effect of calcium on cardiac phosphorylase activation, contractile force and cyclic AMP in euthyroid and hyperthyroid rat hearts

1976 ◽  
Vol 54 (4) ◽  
pp. 590-595 ◽  
Author(s):  
Elizabeth J. Hartley ◽  
John H. McNeill
Keyword(s):  
Enzyme Activity ◽  
Thyroid Hormone ◽  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Chronotropic Effect ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Isolated Perfused Rat Hearts

Calcium chloride injected into isolated perfused rat hearts produced a positive inotropic effect and increased the levels of phosphorylase a (EC 2.4.1.1). The increase in enzyme activity lagged behind the inotropic effect. Pretreatment of animals with thyroid hormone enhanced the ability of noradrenaline to activate phosphorylase but did not affect the inotropic or phosphorylase activating effect of calcium. Thyroid hormone pretreatment did enhance the chronotropic effect of calcium. Calcium did not affect the cardiac levels of cyclic AMP. It is concluded that calcium can activate phosphorylase by a mechanism other than cyclic AMP and that the enhancement of adrenergic amine-induced phosphorylase activation by thyroid hormone is not a calcium mediated event.

200 years of digitalis: the emerging central role of the sodium ion in the control of cardiac force

1985 ◽  
Vol 249 (5) ◽  
pp. C367-C378 ◽  
Author(s):  
C. O. Lee
Keyword(s):  
Cardiac Muscle ◽  
Time Course ◽  
Positive Inotropic Effect ◽  
Quantitative Relationship ◽  
Complete Recovery ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Parallel Increase ◽  
Small Rise ◽  
High Concentrations

Digitalis has been used therapeutically for two centuries, but the mechanism by which it enhances the ability of cardiac muscle to produce force (the positive inotropic effect) has not been fully elucidated. The major controversy concerns the question of whether the inhibition of the Na+-K+ pump by digitalis, particularly at low (therapeutic) concentrations, increases the intracellular Na+ concentration and thus is causally related to the positive inotropic effect. Na+-selective microelectrodes, introduced recently, have made it possible to measure small changes in intracellular Na+ activity (aiNa) in beating preparations of cardiac muscle and, in particular, to follow the exact time course of change in both aiNa and contractile force during the positive inotropic effect of digitalis. It has been demonstrated that digitalis at low and high concentrations produces a parallel increase in aiNa and in contractile force during the onset of its effect; washout of the drug results in a parallel and complete recovery of aiNa and contractile force. Additional strong evidence for a correlation between the pump inhibition and digitalis inotropy is the fact that the magnitude of increase in aiNa and contractile force produced by digitalis depends on the level of aiNa and therefore on the rate of Na+ extrusion by the Na+-K+ pump. The study on the quantitative relationship between aiNa and contractile force reveals that the force of contraction is a power function of aiNa, such that a small rise in aiNa produces a significant increase in contractile force. Direct measurements of aiNa and intracellular free Ca2+ during digitalis inotropy strongly support the hypothesis that an increase in aiNa raises intracellular Ca2+ via Na+-Ca2+ exchange, thus producing the positive inotropic effect. In conclusion, the recent data available from the simultaneous and continuous measurements of aiNa and contractile force strongly indicate that the inhibition of the Na+-K+ pump is causally related to the positive inotropic effect of digitalis on cardiac muscle.

Developmental increase in the inotropic and cyclic AMP response to isoproterenol in embryonic and newly hatched chicks

1989 ◽  
Vol 67 (9) ◽  
pp. 1109-1111 ◽  
Author(s):  
Ken Nakazawa ◽  
Yutaka Kusuya ◽  
Koki Shigenobu
Keyword(s):  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Developmental Stages ◽  
Sympathetic Innervation ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Chick Embryos

The cyclic adenosine 3′,5′-monophosphate (cyclic AMP) levels of ventricles isolated from 15- to 20-day-old chick embryos and 0- to 3-day-old hatched chicks were compared to clarify the mechanism underlying the change in sensitivity to isoproterenol during perinatal developmental stages when the functional sympathetic innervation has been completely achieved. Isoproterenol produced a positive inotropic effect on ventricles isolated from both embryonic and hatched chicks, but the ventricles from the hatched chicks were more sensitive. At both developmental stages sotalol was an equipotent antagonist of isoproterenol. 3-Isobutyl-1-methylxanthine (IBMX) produced an increment in the contractile force of the ventricles at both stages, but the ventricles from the hatched chicks responded to lower doses of IBMX. The reactivity to isoproterenol in increasing cyclic AMP level was significantly higher in the hatched ventricles than in the embryonic ventricles. The results suggest that the different sensitivities to isoproterenol between embryonic and newly hatched chick ventricles may be due to some changes in the process for cyclic AMP production.Key words: chick ventricle, development, β-adrenergic sensitivity, cyclic AMP.

Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae

2001 ◽  
Vol 101 (6) ◽  
pp. 637-643 ◽  
Author(s):  
Ole SAETRUM OPGAARD ◽  
Mikael KNUTSSON ◽  
René DE VRIES ◽  
Beril TOM ◽  
Pramod R. SAXENA ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Vasoactive Intestinal Peptide ◽  
Right Atrium ◽  
Human Heart ◽  
Positive Inotropic Effect ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
The Right ◽  
Ventricular Trabeculae

The aim of the present study was to assess the inotropic effects of vasoactive intestinal peptide (VIP) on isolated myocardial trabeculae from the right atrium and the left ventricle of human hearts. Furthermore, using reverse transcriptase-PCR, we wanted to determine the presence of mRNAs encoding the three cloned human VIP receptors, VPAC1, VPAC2 and PAC1. The trabeculae were paced at 1.0Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. VIP had a potent positive inotropic effect in some of the atrial and ventricular trabeculae tested. This effect was almost completely blocked by the VIP-receptor antagonist VIP-(6-28). mRNAs encoding the human VPAC1, VPAC2 and PAC1 receptors were detected in human myocardial trabeculae from both the right atrium and the left ventricle. In conclusion, VIP has a direct positive inotropic effect in both the atria and the ventricles of the human heart. The presence of mRNAs for the VPAC1, VPAC2 and PAC1 receptors suggest that VIP may mediate its effect via these receptors.

scholarly journals Adenosine inhibits the positive inotropic effect of 3-isobutyl-1-methylxanthine in papillary muscles without effect on cyclic AMP or cyclic GMP

1988 ◽  
Vol 93 (4) ◽  
pp. 729-738 ◽  
Author(s):  
Michael Böhm ◽  
Reinhard Brückner ◽  
Joachim Neumann ◽  
Monika Nose ◽  
Wilhelm Schmitz ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles

scholarly journals The Differential Effects of a Selective Kappa-Opioid Receptor Agonist, U50488, in Guinea Pig Heart Tissues

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Chi-Feng Hung ◽  
Hsin-Ju Li ◽  
Hsun-Hao Chang ◽  
Gon-Ann Lee ◽  
Ming Jai Su
Keyword(s):  
Guinea Pig ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Right Atrium ◽  
Receptor Agonist ◽  
Negative Inotropic Effect ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Opioid Receptor Agonist ◽  
Right Atria

The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selectiveκ-receptor antagonist, and pertussis toxin (PTX) abolished the negative inotropic effect of U50488. In contrast, the inhibitory effect was not affected by the pretreatment of atropine or propranolol. Even though U50488 exerted a negative inotropic effect in the left atrium, it did not affect the contractile force of the right atrium and ventricles paced at 2 Hz. Similarly, the beating rate of the spontaneously beating right atrium was also unaffected by U50488. These results indicate that the activation ofκ-opioid receptors can only produce negative inotropic effect in left atria via activation of PTX-sensitive G protein in guinea pigs. The absence of negative inotropic effects in right atria and ventricles suggests that there may be a greater distribution of functionalκ-opioid receptors in guinea pig left atria than in right atria and ventricles, and the distribution of the receptors may be species-specific.

A positive inotropic effect of adenosine in cardiac preparations of right atria from diseased human hearts

2008 ◽  
Vol 379 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Ulrich Gergs ◽  
Peter Boknik ◽  
Wilhelm Schmitz ◽  
Andreas Simm ◽  
Rolf-Edgar Silber ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Right Atria
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