Enhanced Contractile Responsiveness to Cytosolic Ca2+by Delta-2 Opioid Agonist Deltorphin in Intact Guinea Pig Hearts

Fujita, Satoshi; Smart, Steven C.; Stowe, David F.

doi:10.1006/jmcc.2000.1199

Cited by 15 publications

(2 citation statements)

References 34 publications

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“…Others have measured systolic-diastolic [Ca 2ϩ ] (phasic [Ca 2ϩ ]) and contractile force in intact hearts using Ca 2ϩ -sensitive fluorescence probes (6,15,29). We have compared simultaneous changes in phasic [Ca 2ϩ ] and left ventricular (LV) pressure (LVP) (3,18,49,56) and their peak positive and negative derivatives (11) in hearts under normoxic and ischemic conditions. Ischemia and cardiotonic drugs alter the relationships between cytosolic Ca 2ϩ and contractility and relaxation.…”

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confidence: 99%

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Camara

Chen²,

Rhodes³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Negative inotropic agents may differentially modulate indexes of cytosolic [Ca(2+)]-left ventricular (LV) pressure (LVP) relationships when given before and after ischemia. We measured and calculated [Ca(2+)], LVP, velocity ratios [[(d[Ca(2+)]/dt(max))/(dLVP/dt(max)); VR(max)] and [(d[Ca(2+)]/dt(min))/(dLVP/dt(min)); VR(min)]], and area ratio (AR; area [Ca(2+)]/area LVP per beat) before and after global ischemia in guinea pig isolated hearts. Ca(2+) transients were recorded by indo 1-AM fluorescence via a fiberoptic probe placed at the LV free wall. [Ca(2+)]-LVP loops were acquired by plotting LVP as a function of [Ca(2+)] at multiple time points during the cardiac cycle. Hearts were perfused with bimakalim, 2,3-butanedione monoxime (BDM), nifedipine, or lidocaine before and after 30 min of ischemia. Before ischemia, each drug depressed LVP, but only nifedipine decreased both LVP and [Ca(2+)] with a downward and leftward shift of the [Ca(2+)]-LVP loop. After ischemia, each drug depressed LVP and [Ca(2+)] with a downward and leftward shift of the [Ca(2+)]-LVP loop. Each drug except BDM decreased d[Ca(2+)]/dt(max); nifedipine decreased d[Ca(2+)]/dt(min), whereas lidocaine increased it, and bimakalim and BDM had no effect on d[Ca(2+)]/dt(min). Each drug except bimakalim increased VR(max) and VR(min) before ischemia; after ischemia, only BDM and nifedipine increased VR(max) and VR(min). Before and after ischemia, BDM and nifedipine increased AR, whereas lidocaine and bimakalim had no effect. At 30 min of reperfusion, control hearts exhibited marked Ca(2+) overload and depressed LVP. In each drug-pretreated group Ca(2+) overload was reduced on reperfusion, but only the group pretreated with nifedipine exhibited both higher LVP and lower [Ca(2+)]. These results show that negative inotropic drugs are less capable of reducing [Ca(2+)] after ischemia so that there is a relatively larger Ca(2+) expenditure for contraction/relaxation after ischemia than before ischemia. Moreover, the differential effects of pretreatment with negative inotropic drugs on [Ca(2+)]-LVP relationships after ischemia suggest that these drugs, especially nifedipine, can elicit cardiac preconditioning.

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confidence: 99%

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Camara

Chen²,

Rhodes³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…There are studies showing that DOR agonist depressed cardiac function in Bio 14.6 hamster (3), while others demonstrated the escalation of cardiac contractility (9, 22). There is also a report showing that both DOR agonists and antagonists have negative inotropism (23).…”

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confidence: 99%

Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

Nguyen¹,

Guillory

et al. 2012

Peptides

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Cardiac epinephrine and calcitonin gene-related peptide (CGRP) are produced by intrinsic cardiac adrenergic cells (ICA cells) residing in human and animal hearts. ICA cells are neuroparicine cells expressing δ-opioid receptors (DOR). We hypothesized that δ-opioid stimulation of ICA cells enhances epinephrine and CGRP release, which results in the augmentation of heart contraction. Methods Rats were injected with DOR-agonist DPDPE (100 μg/kg) with or without 10-min pretreatment with either β-adrenergic receptor (β-AR) blocker propranolol (2 mg/kg) or CGRP-receptor (CGRPR) blocker CGRP8-37 (300 μg/kg), or their combination. Hemodynamics were monitored with echocardiogram and systolic blood pressure (SBP) was monitored via a tail arterial catheter. Results Changes in left ventricular fraction-shortening (LVFS) and heart rate (HR) were observed at 5-min after DPDPE infusion. At 5-min DPDPE induced a 36±18% (p<0.001) increase of the LVFS, which continues to increase to 51±24% (p<0.0001) by 10 min, and 68±19% (p<0.001) by 20 min. The increase in LVFS was accompanied by the decrease of HR by 9±5% (p<0.01) by 5 min and 11±6% (p<0.001) by 15 min post DPDPE infusion. This magnitude of HR reduction was observed for the remainder of the 20 min. Despite the HR-reduction, cardiac output was increased by 17±8% (p<0.05) and 28±5% (p<0.001) by 5- and 20-min post DPDPE administration, respectively. There was a modest (9±9%, p=0.03) decrease in SBP that was not apparent until 20 min post DPDPE infusion. The positive inotropism of DPDPE was abrogated in animals pretreated with propranolol, CGRP8-37, or combined propranolol+CGRP8-37. Furthermore, in whole animal and cardiomyocyte cell culture preparations, DPDPE induced myocardial protein-kinase A (PKA) activation which was abrogated in the animals pretreated with propranolol+CGRP8-37. Conclusion DOR agonists augment myocardial contraction through enhanced β-AR and CGRPR co-signaling.

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Effects of μ-Opioid Receptor Agonist DAMGO on Heart Contractility and Necrotic Injury to Cardiomyocytes during Ischemia and Reperfusion of Isolated Rat Heart

2015

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We studied the effects of μ-opioid receptor activation in vivo and in vitro on the tolerance of isolated perfused rat heart to global ischemia (45 min) and reperfusion (30 min). Stimulation of μ-receptors in vivo by intraperitoneal administration of μ-opioid receptor agonist DAMGO (0.1 mg/kg) reduced reperfusion release of creatinine phosphokinase and promoted aggravation of postischemic systolic and diastolic dysfunction of the isolated heart. Activation of μ-opioid receptors in vitro by addition of selective agonist DAMGO in a concentration of 170 nM to perfusion solution had no effect on necrotic death of cardiomyocytes and aggravated reperfusion stunning of the heart.

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Enhanced Contractile Responsiveness to Cytosolic Ca2+by Delta-2 Opioid Agonist Deltorphin in Intact Guinea Pig Hearts

Cited by 15 publications

References 34 publications

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

Effects of μ-Opioid Receptor Agonist DAMGO on Heart Contractility and Necrotic Injury to Cardiomyocytes during Ischemia and Reperfusion of Isolated Rat Heart

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Enhanced Contractile Responsiveness to Cytosolic Ca2+by Delta-2 Opioid Agonist Deltorphin in Intact Guinea Pig Hearts

Cited by 15 publications

References 34 publications

Negative inotropic drugs alter indexes of cytosolic [Ca2+]-left ventricular pressure relationships after ischemia

Negative inotropic drugs alter indexes of cytosolic [Ca2+]-left ventricular pressure relationships after ischemia

Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling

Effects of μ-Opioid Receptor Agonist DAMGO on Heart Contractility and Necrotic Injury to Cardiomyocytes during Ischemia and Reperfusion of Isolated Rat Heart

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Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia

Negative inotropic drugs alter indexes of cytosolic [Ca²⁺]-left ventricular pressure relationships after ischemia