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Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats
Author(s) -
Bae Soochan,
Gilbert Raymond D.,
Ducsay Charles A.,
Zhang Lubo
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.082701
Subject(s) - offspring , medicine , prenatal cocaine exposure , endocrinology , ischemia , saline , gestation , myocardial infarction , pregnancy , physiology , biology , prenatal exposure , genetics
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.