Prostaglandin E2 does not attenuate adrenergic-induced cardiac contractile response
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Prostaglandin E2 does not attenuate adrenergic-induced cardiac contractile response. / Pecha, Simon; Mudersbach, Eileen; Söhren, Klaus-Dieter; Hakmi, Samer; Reichenspurner, Hermann; Eschenhagen, Thomas; Christ, Torsten.
in: N-S ARCH PHARMACOL, Jahrgang 387, Nr. 10, 2014, S. 963-968.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Prostaglandin E2 does not attenuate adrenergic-induced cardiac contractile response
AU - Pecha, Simon
AU - Mudersbach, Eileen
AU - Söhren, Klaus-Dieter
AU - Hakmi, Samer
AU - Reichenspurner, Hermann
AU - Eschenhagen, Thomas
AU - Christ, Torsten
PY - 2014
Y1 - 2014
N2 - Systemic inflammation may contribute to heart failure. PGE2 was recently suggested to mediate inflammation-induced impairment of cardiac function by desensitizing the murine heart to isoprenaline. Given the magnitude of the reported effect and the potential relevance, we sought to reproduce it in the human heart. Human trabeculae were prepared from the right atrial tissue obtained during heart surgery and from the right ventricle of two explanted human failing hearts. Muscle strips were electrically driven and isometric force development was measured. PGE2 was given at a single concentration (0.1 μM). Norepinephrine was used to activate β1-adrenoceptors, epinephrine to activate β2-adrenoceptors in atrial trabeculae. Isoprenaline was used in ventricular tissue. All patients were in sinus rhythm. Murine ventricular strips were used for comparison and stimulated with isoprenaline. The pharmacological activity of the PGE2 batch was confirmed by assessing concentration-dependent vasoconstriction in murine aorta. We used atrial and ventricular trabeculae from humans. Exposure to PGE2 (15 min) did not affect contractility when compared to time-matched controls. PGE2 neither altered the sensitivity or efficacy of β1- or β2-adrenoceptor-mediated stimulation of force in human atrial or in ventricular trabeculae for nonselective β1- or β2-adrenoceptor-stimulation. Surprisingly, PGE2 also did not affect -logEC50 values or maximum catecholamine-stimulated force in ventricular strips from mice, whereas it induced vasoconstriction in aortic rings with an -logEC50 of 5.0 (n = 6). Our data do not support a role for PGE2 in regulating catecholamine inotropy, neither in mice nor in humans.
AB - Systemic inflammation may contribute to heart failure. PGE2 was recently suggested to mediate inflammation-induced impairment of cardiac function by desensitizing the murine heart to isoprenaline. Given the magnitude of the reported effect and the potential relevance, we sought to reproduce it in the human heart. Human trabeculae were prepared from the right atrial tissue obtained during heart surgery and from the right ventricle of two explanted human failing hearts. Muscle strips were electrically driven and isometric force development was measured. PGE2 was given at a single concentration (0.1 μM). Norepinephrine was used to activate β1-adrenoceptors, epinephrine to activate β2-adrenoceptors in atrial trabeculae. Isoprenaline was used in ventricular tissue. All patients were in sinus rhythm. Murine ventricular strips were used for comparison and stimulated with isoprenaline. The pharmacological activity of the PGE2 batch was confirmed by assessing concentration-dependent vasoconstriction in murine aorta. We used atrial and ventricular trabeculae from humans. Exposure to PGE2 (15 min) did not affect contractility when compared to time-matched controls. PGE2 neither altered the sensitivity or efficacy of β1- or β2-adrenoceptor-mediated stimulation of force in human atrial or in ventricular trabeculae for nonselective β1- or β2-adrenoceptor-stimulation. Surprisingly, PGE2 also did not affect -logEC50 values or maximum catecholamine-stimulated force in ventricular strips from mice, whereas it induced vasoconstriction in aortic rings with an -logEC50 of 5.0 (n = 6). Our data do not support a role for PGE2 in regulating catecholamine inotropy, neither in mice nor in humans.
U2 - 10.1007/s00210-014-1012-2
DO - 10.1007/s00210-014-1012-2
M3 - SCORING: Journal article
C2 - 24974239
VL - 387
SP - 963
EP - 968
JO - N-S ARCH PHARMACOL
JF - N-S ARCH PHARMACOL
SN - 0028-1298
IS - 10
ER -