title: Inhibition of the nitric oxide/cyclic guanosine monophosphate pathway limited the cardioprotective effect of post-conditioning in hearts with apical myocardial infarction.
abstract: Reperfusion damage involves opening of the mitochondrial permeability transition pore (mPTP) and loss of ATP synthesis. Several cardioprotective pathways are activated by ischemic or pharmacological post-conditioning (PC). The mechanisms that are activated by PC in no co-morbidity murine models include: activation of rescue kinases, oxidative stress reduction, glycolytic flux regulation and preservation of ATP synthesis. However, relatively scarce efforts have been made to define whether the efficacy of PC signaling is blunted by risk factors or systemic diseases associated with ischemic heart pathology. Experimental evidence has shown that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling is a main mechanism activated by PC in hearts without pathological history. In this work we evaluated the participation of the NO pathway, through downstream kinase activation and inhibition of mPTP in hearts with previous infarct. Myocardial infarction was induced with a single dose of isoproterenol (85 mg/kg i.p.) to male Wistar rats. After 24 h, the hearts were mounted into the Langendorff system and subjected to 30 min of ischemia and 60 min of reperfusion. PC consisted of 5 cycles of 30 s of reperfusion/30 s of ischemia, then the hearts were reperfused with or without inhibitors of the NO/cGMP pathway. PC activates the NO/cGMP pathway, as increased cGMP and NO levels were detected in isoproterenol-treated hearts. The cardioprotective effect of PC was abolished with both L-NAME (inhibitor of constitutive NO synthase) and ODQ (inhibitor of soluble guanylate cyclase), whereas the NO donor (DETA-NO) restored cardioprotection even in the presence of L-NAME or ODQ. We also found that mitochondrial structure and function was preserved in PC hearts. We conclude that PC exerts cardioprotection in hearts with previous infarct by maintaining mitochondrial structure and function through NO-dependent pathway.
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, I. Ch., Juan Badiano No. 1., Col. Sección XVI, México D.F. 14080, Mexico. Electronic address: glicoproteico@gmail.com.
authors.forename: Francisco
authors.initials: F
authors.lastname: Correa
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, I. Ch., Juan Badiano No. 1., Col. Sección XVI, México D.F. 14080, Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., Mexico.
authors.forename: Victoria
authors.initials: V
authors.lastname: Chagoya
authors.affiliation: Centro de Innovación y Transferencia en Salud de la Escuela de Medicina del Tecnológico de Monterrey, Cátedra de Cardiología y Medicina Vascular, Instituto de Cardiología y Medicina Vascular del Tecnológico de Monterrey, Monterrey, N.L. 64710, Mexico.
authors.forename: Gerardo
authors.initials: G
authors.lastname: García-Rivas
authors.affiliation: Laboratorio de Histomorfología, Torre de Investigación, Instituto Nacional de Pediatría, SS, México D.F. 04530, Mexico.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Vigueras
authors.affiliation: Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, 04510 México DF, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, I. Ch., Juan Badiano No. 1., Col. Sección XVI, México D.F. 14080, Mexico.
authors.forename: Wylly Ramsés
authors.initials: WR
authors.lastname: García-Niño
authors.affiliation: Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco De Quiroga 15, Tlalpan, México D.F., Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Sección de Patología Experimental, Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco De Quiroga 15, Tlalpan, México D.F., Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: León-Contreras
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, I. Ch., Juan Badiano No. 1., Col. Sección XVI, México D.F. 14080, Mexico.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
mesh_terms: D000818:Animals; D006157:Guanosine Monophosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D006157:Guanosine Monophosphate; D019331:NG-Nitroarginine Methyl Ester
keywords: Isoproterenol; Post-conditioning; Reperfusion injury; cGMP