Positive inotropic effect of α-adrenergic stimulation in intact dog hearts

1979 ◽  
Vol 43 (2) ◽  
pp. 381
Keyword(s):  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Adrenergic Stimulation

scholarly journals Na+/Ca2+ exchanger overexpression impairs frequency- and ouabain-dependent cell shortening in adult rat cardiomyocytes

2004 ◽  
Vol 287 (4) ◽  
pp. H1435-H1445 ◽  
Author(s):  
Birgit Bölck ◽  
Götz Münch ◽  
Peter Mackenstein ◽  
Martin Hellmich ◽  
Ingo Hirsch ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gene Transfer ◽  
Mode Of Action ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Adrenergic Stimulation ◽  
Human Heart Failure ◽  
Rat Cardiomyocytes ◽  
Cell Shortening ◽  
Reverse Mode

The Na+/Ca2+ exchanger (NCX) may influence cardiac function depending on its predominant mode of action, forward mode or reverse mode, during the contraction-relaxation cycle. The intracellular Na+ concentration ([Na+]i) and the duration of the action potential as well as the level of NCX protein expression regulate the mode of action of NCX. [Na+]i and NCX expression have been reported to be increased in human heart failure. Nevertheless, the consequences of altered NCX expression in heart failure are still a matter of discussion. We aimed to characterize the influence of NCX expression on intracellular Ca2+ transport in rat cardiomyocytes by adenoviral-mediated gene transfer. A five- to ninefold (dose dependent) overexpression of NCX protein was achieved after 48 h by somatic gene transfer (Ad.NCX.GFP) versus control (Ad.GFP). NCX activity, determined by Na+ gradient-dependent 45Ca2+-uptake, was significantly increased. The protein expressions of sarco(endo)plasmic reticulum Ca2+-ATPase, phospholamban, and calsequestrin were unaffected by NCX overexpression. Fractional shortening (FS) of isolated cardiomyocytes was significantly increased at low stimulation rates in Ad.NCX.GFP. After a step-wise enhancing frequency of stimulation to 3.0 Hz, FS remained unaffected in Ad.GFP cells but declined in Ad.NCX.GFP cells. The positive inotropic effect of the cardiac glycoside ouabain was less effective in Ad.NCX.GFP cells, whereas the positive inotropic effect of β-adrenergic stimulation remained unchanged. In conclusion, NCX overexpression results in a reduced cell shortening at higher stimulation frequencies as well as after inhibition of sarcolemmal Na+-K+-ATPase, i.e., in conditions with enhanced [Na+]i. At low stimulation rates, increased NCX expression enhances both intracellular systolic Ca2+ and contraction amplitude.

Overexpression of Cyclic Adenosine Monophosphate Effluent Protein MRP4 Induces an Altered Response to β-Adrenergic Stimulation in the Senescent Rat Heart

2015 ◽  
Vol 122 (2) ◽  
pp. 334-342 ◽  
Author(s):  
Aude Carillion ◽  
Sarah Feldman ◽  
Cheng Jiang ◽  
Fabrice Atassi ◽  
Na Na ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Cyclic Adenosine Monophosphate ◽  
Calcium Transient ◽  
Adenosine Monophosphate ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Inotropic Response ◽  
Adrenergic Stimulation

Abstract Background: In the senescent heart, the positive inotropic response to β-adrenoceptor stimulation is reduced, partly by dysregulation of β1- and β3-adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the control of intracellular cyclic adenosine monophosphate concentration by controlling its efflux but the role of MRP4 in the β-adrenergic dysfunction of the senescent heart remains unknown. Methods: The β-adrenergic responses to isoproterenol were investigated in vivo (stress echocardiography) and in vitro (isolated cardiomyocyte by Ionoptix® with sarcomere shortening and calcium transient) in young (3 months old) and senescent (24 months old) rats pretreated or not with MK571, a specific MRP4 inhibitor. MRP4 was quantified in left ventricular homogenates by Western blotting. Data are mean ± SD expressed as percent of baseline value. Results: The positive inotropic effect of isoproterenol was reduced in senescent rats in vivo (left ventricular shortening fraction 120 ± 16% vs. 158 ± 20%, P < 0.001, n = 16 rats) and in vitro (sarcomere shortening 129 ± 37% vs. 148 ± 35%, P = 0.004, n = 41 or 43 cells) as compared to young rats. MRP4 expression increased 3.6-fold in senescent compared to young rat myocardium (P = 0.012, n = 8 rats per group). In senescent rats, inhibition of MRP4 by MK571 restored the positive inotropic effect of isoproterenol in vivo (143 ± 11%, n = 8 rats). In vitro in senescent cardiomyocytes pretreated with MK571, both sarcomere shortening (161 ± 45% vs. 129 ± 37%, P = 0.007, n = 41 cells per group) and calcium transient amplitude (132 ± 25% vs. 113 ± 27%, P = 0.007) increased significantly. Conclusion: MRP4 overexpression contributes to the reduction of the positive inotropic response to β-adrenoceptor stimulation in the senescent heart.

scholarly journals Oxidation of ryanodine receptor after ischemia-reperfusion increases propensity of Ca2+ waves during β-adrenergic receptor stimulation

2018 ◽  
Vol 315 (4) ◽  
pp. H1032-H1040 ◽  
Author(s):  
Elisa Bovo ◽  
Stefan R. Mazurek ◽  
Aleksey V. Zima
Keyword(s):  
Oxidative Stress ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Adrenergic Receptor ◽  
Positive Inotropic Effect ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Inotropic Effect ◽  
Adrenergic Stimulation ◽  
Promising Strategy

β-Adrenergic receptor (β-AR) activation produces the main positive inotropic response of the heart. During ischemia-reperfusion (I/R), however, β-AR activation can trigger life-threatening arrhythmias. Because I/R is frequently associated with oxidative stress, we investigated whether ryanodine receptor (RyR) oxidation contributes to proarrythmogenic Ca2+ waves during β-AR activation. Measurements of contractile and electrical activity from Langendorff-perfused rabbit hearts revealed that I/R produces tachyarrhythmias. Ventricular myocytes isolated from I/R hearts had an increased level of oxidized glutathione (i.e., oxidative stress) and a decreased level of free thiols in RyRs (i.e., RyR oxidation). Furthermore, myocytes from I/R hearts were characterized by increased sarcoplasmic reticulum (SR) Ca2+ leak and enhanced fractional SR Ca2+ release. In myocytes from nonischemic hearts, β-AR activation with isoproterenol (10 nM) produced only a positive inotropic effect, whereas in myocytes from ischemic hearts, isoproterenol at the same concentration triggered spontaneous Ca2+ waves. β-AR activation produced a similar effect on RyR phosphorylation in control and I/R myocytes. Treatment of myocytes from I/R hearts with the reducing agent mercaptopropionylglycine (100 μM) attenuated RyR oxidization and decreased Ca2+ wave frequency during β-AR activation. On the other hand, treatment of myocytes from nonischemic hearts with H2O2 (50 μM) increased SR Ca2+ leak and triggered Ca2+ waves during β-AR activation. Collectively, these results suggest that RyR oxidation after I/R plays a critical role in the transition from positive inotropic to arrhythmogenic effects during β-AR stimulation. Prevention of RyR oxidation can be a promising strategy to inhibit arrhythmias and preserve positive inotropic effect of β-AR activation during myocardial infarction. NEW & NOTEWORTHY Oxidative stress induced by ischemia plays a critical role in triggering arrhythmias during adrenergic stimulation. The combined increase in sarcoplasmic reticulum Ca2+ leak (because of ryanodine receptor oxidation) and sarcoplasmic reticulum Ca2+ load (because of adrenergic stimulation) can trigger proarrythmogenic Ca2+ waves. Restoring normal ryanodine receptor redox status can be a promising strategy to prevent arrhythmias and preserve positive inotropic effect of adrenergic stimulation during myocardial infarction.

The inotropic effect of nitric oxide on mammalian papillary muscle is dependent on the level of β1-adrenergic stimulation

2002 ◽  
Vol 80 (6) ◽  
pp. 569-577 ◽  
Author(s):  
S A Reading ◽  
J K Barclay
Keyword(s):  
Nitric Oxide ◽  
Cardiac Muscle ◽  
Papillary Muscle ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Adrenergic Stimulation ◽  
No Donor ◽  
Bicarbonate Buffer ◽  
Inotropic Effects ◽  
Cgmp Analog

We tested the hypothesis that nitric oxide has a positive inotropic effect on mammalian cardiac muscle contractility and that this effect sums with the positive inotropic effect of β1-adrenergic agonists when both are present. Feline right ventricular papillary muscles were stimulated to contract isometrically at 0.2 Hz in Krebs–Henseleit bicarbonate buffer (KREBS) gassed with 95% O2 and 5% CO2 (26°C; pH 7.34). The nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP, 10–5 M), and the membrane permeable cGMP analog 8-bromoguanosine-3',5'-cyclo phosphate sodium (Br-cGMP, 10–5 M), significantly increased developed force by 13.3 ± 1.5% (n = 11) and 7.8 ± 2.8% (n = 7), respectively. SNAP, at 10-5 M, significantly increased the force developed by papillary muscle treated with 10–11 M or 10–9 M dobutamine hydrochloride (a β1-adrenergic agonist) (n = 25, 11.3 ± 2.9% and 10.0 ± 3.6%, respectively) when compared with the addition of KREBS (n = 27, 2.6 ± 0.9% and 5.5 ± 0.9%), but the increase was less than predicted by the sum of inotropic effects of SNAP and dobutamine. SNAP at 10-5 M did not change developed force in muscles treated with 10–7 M dobutamine but it significantly decreased developed force in muscles challenged with 10–5 M dobutamine (n = 18, 29.3 ± 5.0%) when compared with KREBS (n = 10, 41.5 ± 6.8%). Similarly, 10–4 M 8-bromo-adenosine cyclic 3',5'-hydrogen phosphate monosodium (a membrane permeable cAMP analog) increased developed force 14.9 ± 3.3% and the addition of 10–5 M Br-cGMP to those muscles significantly reduced developed force by 3.5% ± 1.1% (n = 7). Thus, the positive inotropic effect of NO decreased and ultimately became an attenuation as the level of β1-adrenergic stimulation increased due, at least in part, to an interaction between the cAMP and cGMP second messenger pathways.Key words: nitric oxide, β1-adrenergic, cGMP, cAMP, contractility, cardiac muscle.

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