Endogenous norepinephrine stimulates both α1- and β-adrenoceptors in myocardium from children with congenital heart defects

Borthne, Kjell; Hågå, P; Langslet, A; Lindberg, Harald; Skomedal, Tor; Osnes, Jan‐Bjørn

doi:10.1016/s0022-2828(08)80060-0

Cited by 15 publications

(11 citation statements)

References 7 publications

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“…This effect may be due to a direct effect on cardiac β receptors [42] and/or via release of endogenous norepinephrine [43], [44]. In the present study, we demonstrated that dobutamine increased cardiac contractility and heart rate.…”

Section: Discussionsupporting

confidence: 63%

Cardiac Peroxisome Proliferator-Activated Receptor δ (PPARδ) as a New Target for Increased Contractility without Altering Heart Rate

et al. 2013

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Background and AimsAgents having a positive inotropic effect on the heart are widely used for the treatment of heart failure. However, these agents have the side effect of altering heart rate. It has been established that peroxisome proliferator-activated receptor δ (PPARδ) is mediated in cardiac contraction, however the effect on heart rate is unknown. Thus, we used an agonist of PPARδ, GW0742, to investigate this issue in the present study.Methods and ResultsWe used isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats to measure the actions of GW0742 extra-vivo and in vivo. In diabetic rats with heart failure, GW0742 at a dose sufficient to activate PPARδ reversed cardiac contraction without changes in heart rate. In normal rats, PPARδ enhanced cardiac contractility and hemodynamic dP/dtmax significantly more than dobutamine. Both actions were diminished by GSK0660 at a dose enough to block PPARδ. However, GW0742 at the same dose failed to modify heart rate, although it did produce a mild increase in blood pressure. Detection of intracellular calcium level and Western blotting analysis showed that the intracellular calcium concentration and troponin I phosphorylation were both enhanced by GW0742.ConclusionActivation of PPARδ by GW0742 increases cardiac contractility but not heart rate. Thus, PPARδ may be a suitable target for the development of inotropic agents to treat heart failure without changing heart rate.

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Section: Discussionsupporting

confidence: 63%

Cardiac Peroxisome Proliferator-Activated Receptor δ (PPARδ) as a New Target for Increased Contractility without Altering Heart Rate

et al. 2013

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“…In earlier papers ( Borthne et al . 1994 , Borthne et al . 1995 ) we showed that field stimulated atrial myocardial preparations from children with congenital heart defects were influenced by the endogenous transmitter noradrenaline, probably released from sympathetic nerve endings by the electric field pulses used to drive the myocardial trabeculae.…”

Section: Discussionmentioning

confidence: 99%

“…We previously showed that in field stimulated atrial myocardial specimens from children operated for congenital heart defects, a substantial inotropic effect was exerted by endogenous noradrenaline, probably released by concomitant stimulation of sympathetic nerves in the muscle preparation ( Borthne et al . 1994 , Borthne et al . 1995 ).…”

mentioning

confidence: 99%

Endogenous muscarinic activity attenuates adrenergic inotropic effects in field stimulated atrial myocardium from children with congenital heart defects

Borthne¹,

Langslet²,

Lindberg

et al. 1999

Acta Physiologica Scandinavica

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To analyse the possible influence of endogenous muscarinic activity on the inotropic effects of endogenously released noradrenaline in field stimulated myocardial preparations from atria of children with congenital heart defects, we studied the maximal effect of the muscarinic antagonist atropine (1.5 micromol L(-1)). Maximal force of contraction increased by 12.8 +/- 2.0% (SEM), while the maximal rate of development of the force increased by 16.7 +/- 2.7% (SEM). Time to half maximal developed force was 57 +/- 5 s (SEM). Time to peak force, time to relax to the 20% level and relaxation time all decreased significantly after atropine. Compared with endogenous adrenoceptor stimulation alone, the combined effects of partial muscarinic and adrenergic receptor stimulation thus were moderate reductions of the maximal force of contraction and maximal rate of development of the force and increased time to peak force, time to relax to the 20% level and relaxation time. The main effect of the endogenous muscarinic activity probably was to attenuate the effect of the beta-adrenoceptor stimulation. The endogenous muscarinic activity in field stimulated atrial preparations from children is significant, and has to be taken into account in experimental set-ups.

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“…The importance of the cardiac α 1 ‐adrenoreceptor in health and disease has become appreciated only relatively recently. The maximum relative contribution of α 1 ‐adrenoreceptors to nonspecific adrenergic stimulation in human neonates remains unknown, but varies between 0 and 44% in children (38,39). All three α 1 ‐adrenoreceptor subtypes are expressed in neonatal mammalian myocytes, and are activated by norepinephrine (40), though there may be some differences between subtype expression and functionality (41).…”

Section: Adrenergic Receptor Stimulationmentioning

confidence: 99%

“…In addition to developmental changes, haemodynamic status is known to have a significant influence on the relative density and functional expression of cardiac α 1 ‐adrenoreceptors in children (38). Chronic activation of cardiac α 1 ‐adrenoreceptors leads to myocyte hypertrophy, mediated by multiple mitogen‐activated kinases.…”

Section: Adrenergic Receptor Stimulationmentioning

confidence: 99%

Pharmacological support for children with myocardial dysfunction

Booker

2002

Pediatric Anesthesia

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Endogenous norepinephrine stimulates both α1- and β-adrenoceptors in myocardium from children with congenital heart defects

Cited by 15 publications

References 7 publications

Cardiac Peroxisome Proliferator-Activated Receptor δ (PPARδ) as a New Target for Increased Contractility without Altering Heart Rate

Cardiac Peroxisome Proliferator-Activated Receptor δ (PPARδ) as a New Target for Increased Contractility without Altering Heart Rate

Endogenous muscarinic activity attenuates adrenergic inotropic effects in field stimulated atrial myocardium from children with congenital heart defects

Pharmacological support for children with myocardial dysfunction

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