Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats

Journal of Physiology - Tập 565 Số 1 - Trang 149-158 - 2005
Soochan Bae1, Raymond D. Gilbert, Charles A. Ducsay, Li Zhang
1Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA

Tóm tắt

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 PKCɛ and phospho‐PKCɛ 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 PKCɛ gene expression in the male heart may play an important role.

Từ khóa


Tài liệu tham khảo

10.1152/ajpheart.00005.2003

10.1038/sj.bjp.0706129

10.1016/S0093-691X(99)00258-7

10.1161/01.RES.72.4.757

10.1161/hh1001.090858

10.1016/S0008-6363(03)00541-8

10.1073/pnas.191369098

10.1073/pnas.161120198

10.1002/dvdy.1139

10.1096/fj.01-0629com

10.1016/0892-0362(95)00010-O

10.1074/jbc.M311459200

10.3109/00207458509149763

10.1161/01.RES.82.11.1111

10.1161/hh2201.099434

10.1037//0735-7044.109.4.734

10.1161/01.CIR.0000081943.93653.73

10.1016/S0892-0362(99)00058-6

10.1146/annurev.physiol.60.1.309

10.1002/bdd.2510140408

10.1152/ajpheart.00898.2003

10.1016/S1071-5576(03)00074-1

10.1124/jpet.104.073494

10.1016/S0022-3476(05)81842-6

10.1152/ajpheart.2001.281.1.H404

10.1152/ajpheart.00348.2001

10.1161/01.CIR.99.13.1685

10.1111/j.1749-6632.1998.tb09731.x

Mehta SK, 1993, Transient myocardial ischemia in infants prenatally exposed to cocaine, J Pediatr, 122, 945, 10.1016/S0022-3476(09)90025-7

10.1016/0031-9384(94)90083-3

10.1542/peds.113.S3.1058

10.1016/j.abb.2003.08.038

10.1097/00003465-199201000-00003

10.1016/S0008-6363(99)00271-0

10.1111/j.1749-6632.1998.tb08238.x

10.1007/s00424-001-0766-9

10.1161/01.RES.88.1.59

10.1161/01.CIR.96.5.1598

10.1161/01.RES.74.2.299

10.1006/jmcc.2002.2020

10.1152/ajpheart.00247.2004

10.1111/j.1749-6632.1998.tb09728.x

10.1007/BF00439542

10.1016/S0892-0362(02)00194-0

10.1161/hh1001.091864

10.1016/S1071-5576(03)00106-0

Van de Bor M, 1990, Decreased cardiac output in infants of mothers who abused cocaine, Pediatrics, 85, 30, 10.1542/peds.85.1.30

10.2165/00003088-199222020-00001

10.1037//0735-7044.112.2.419

Xiao Y, 2000, Cocaine induces apoptosis in fetal myocardial cells through a mitochondria‐dependent pathway, J Pharmacol Exp Ther, 292, 8

10.1097/00005344-200106000-00001

10.1161/01.CIR.97.3.276

10.1161/01.RES.86.6.692

10.1016/j.jsgi.2004.09.004

Thông tin
Thông tin xuất bản

Journal of Physiology

Tập 565 Số 1

149-158

Thông tin tác giả