title: Prenatal cocaine exposure increases heart susceptibility to ischaemia-reperfusion injury in adult male but not female rats.
abstract: The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia-reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg(-1)) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKCepsilon and phospho-PKCepsilon levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKCepsilon gene expression in the male heart may play an important role.
authors.affiliation: Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
authors.forename: Soochan
authors.initials: S
authors.lastname: Bae
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Gilbert
authors.forename: Charles A
authors.initials: CA
authors.lastname: Ducsay
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D004198:Disease Susceptibility / Q000139:chemically induced / Q000196:embryology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000196:embryology* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011493:Protein Kinase C / Q000378:metabolism; D051744:Protein Kinase C-epsilon; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced* / Q000196:embryology* / Q000503:physiopathology; D012737:Sex Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D011518:Proto-Oncogene Proteins; C497257:Prkce protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D003042:Cocaine