title: Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.
abstract: Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart.
authors.affiliation: Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio b-rorabaugh@onu.edu.
authors.forename: Boyd R
authors.initials: BR
authors.lastname: Rorabaugh
authors.affiliation: Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Seeley
authors.affiliation: Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Bui
authors.affiliation: Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio.
authors.forename: Lisanne
authors.initials: L
authors.lastname: Sprague
authors.affiliation: Raabe College of Pharmacy, Ohio Northern University, Ada, Ohio.
authors.forename: Manoranjan S
authors.initials: MS
authors.lastname: D'Souza
mesh_terms: D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000139:chemically induced / Q000473:pathology; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051744:Protein Kinase C-epsilon / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; C497257:Prkce protein, rat; D051058:Oncogene Protein v-akt; D051744:Protein Kinase C-epsilon
keywords: drug abuse; heart; ischemia; pregnancy; prenatal methamphetamine