We previously reported that melanocortins afford cardioprotection in conditions of experimental myocardial ischemia/reperfusion, with involvement of the janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) signalings. We investigated the influence of the melanocortin analog [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) on short-term detrimental responses to cardiac arrest (CA) induced in rats by intravenous (i.v.) administration of potassium chloride, followed by cardiopulmonary resuscitation (CPR) plus epinephrine treatment. In CA/CPR rats i.v. treated with epinephrine (0.1mg/kg) and returned to spontaneous circulation (48%) we recorded low values of mean arterial pressure (MAP) and heart rate (HR), alteration of hemogasanalysis parameters, left ventricle low expression of the cardioprotective transcription factors pJAK2 and pTyr-STAT3 (JAK-dependent), increased oxidative stress, up-regulation of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and down-regulation of the anti-inflammatory cytokine IL-10, as assessed at 1h and 3h after CPR. On the other hand, i.v. treatment during CPR with epinephrine plus NDP-α-MSH (340μg/kg) almost completely restored the basal conditions of MAP and HR, reversed metabolic acidosis, induced left ventricle up-regulation of pJAK2, pTyr-STAT3 and IL-10, attenuated oxidative stress, down-regulated TNF-α and IL-6 levels, and improved survival rate by 81%. CA/CPR plus epinephrine alone or in combination with NDP-α-MSH did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and pERK1/2 levels. These results indicate that melanocortins improve return to spontaneous circulation, reverse metabolic acidosis, and inhibit heart oxidative stress and inflammatory cascade triggered by CA/CPR, likely via activation of the JAK/STAT signaling pathway.

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest / Ottani, Alessandra; Neri, Laura; Canalini, Fabrizio; Calevro, Anita; Rossi, Rosario; Cappelli, Gianni; Ballestri, M; Giuliani, Daniela; Guarini, Salvatore. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - STAMPA. - 745:(2014), pp. 108-116. [10.1016/j.ejphar.2014.10.022]

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

OTTANI, Alessandra;Neri, Laura;Canalini, Fabrizio;Calevro, Anita;ROSSI, Rosario;CAPPELLI, Gianni;GIULIANI, Daniela;GUARINI, Salvatore
2014

Abstract

We previously reported that melanocortins afford cardioprotection in conditions of experimental myocardial ischemia/reperfusion, with involvement of the janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) signalings. We investigated the influence of the melanocortin analog [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) on short-term detrimental responses to cardiac arrest (CA) induced in rats by intravenous (i.v.) administration of potassium chloride, followed by cardiopulmonary resuscitation (CPR) plus epinephrine treatment. In CA/CPR rats i.v. treated with epinephrine (0.1mg/kg) and returned to spontaneous circulation (48%) we recorded low values of mean arterial pressure (MAP) and heart rate (HR), alteration of hemogasanalysis parameters, left ventricle low expression of the cardioprotective transcription factors pJAK2 and pTyr-STAT3 (JAK-dependent), increased oxidative stress, up-regulation of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and down-regulation of the anti-inflammatory cytokine IL-10, as assessed at 1h and 3h after CPR. On the other hand, i.v. treatment during CPR with epinephrine plus NDP-α-MSH (340μg/kg) almost completely restored the basal conditions of MAP and HR, reversed metabolic acidosis, induced left ventricle up-regulation of pJAK2, pTyr-STAT3 and IL-10, attenuated oxidative stress, down-regulated TNF-α and IL-6 levels, and improved survival rate by 81%. CA/CPR plus epinephrine alone or in combination with NDP-α-MSH did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and pERK1/2 levels. These results indicate that melanocortins improve return to spontaneous circulation, reverse metabolic acidosis, and inhibit heart oxidative stress and inflammatory cascade triggered by CA/CPR, likely via activation of the JAK/STAT signaling pathway.
2014
745
108
116
Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest / Ottani, Alessandra; Neri, Laura; Canalini, Fabrizio; Calevro, Anita; Rossi, Rosario; Cappelli, Gianni; Ballestri, M; Giuliani, Daniela; Guarini, Salvatore. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - STAMPA. - 745:(2014), pp. 108-116. [10.1016/j.ejphar.2014.10.022]
Ottani, Alessandra; Neri, Laura; Canalini, Fabrizio; Calevro, Anita; Rossi, Rosario; Cappelli, Gianni; Ballestri, M; Giuliani, Daniela; Guarini, Salvatore
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1061782
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