Cocaine Decreases Uteroplacental Blood Flow in the Rat

Patel, Tejal G.; Laungani, Rajesh; Grose, Elizabeth A.; Dow-Edwards, Diana

doi:10.1016/s0892-0362(99)00022-7

Cited by 19 publications

(9 citation statements)

References 21 publications

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“…Suppression of PKCε expression results from cocaine-or nicotineinduced methylation of CpG dinucleotide sequences in the promoter region of DNA encoding this cardioprotective protein (24,30,47). A common link between cocaine, nicotine, and methamphetamine is that prenatal use of each of these substances decreases uterine blood flow (9,27,32,33,40,43) and decreases the partial pressure of oxygen in fetal circulation (1,16,42). Fetal hypoxia also decreases cardiac PKCε expression (34) and increases myocardial sensitivity to ischemic injury (26,46) in adult offspring.…”

Section: Discussionmentioning

confidence: 99%

Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts

Rorabaugh

Seeley

Bui

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Rorabaugh BR, Seeley SL, Bui AD, Sprague L, D'Souza MS. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts. Am J Physiol Heart Circ Physiol 310: H516 -H523, 2016. First published December 18, 2015 doi:10.1152/ajpheart.00642.2015-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 Ϫ1 ·day Ϫ1 ) 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 enddiastolic 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. prenatal methamphetamine; ischemia; heart; pregnancy; drug abuse NEW & NOTEWORTHY Prenatal exposure to methamphetamine increases myocardial sensitivity to ischemic injury and alters proteins involved in cardioprotective signaling pathways in the adult female rat heart. These changes were not observed in male hearts. The responses of adult male and female hearts to an ischemic insult are differentially altered by prenatal methamphetamine.METHAMPHETAMINE is one of the most common illicit drugs abused during pregnancy (2, 29). One study found that 5.2% of pregnant women use methamphetamine at some point during their pregnancy (2). Most studies of prenatal methamphetamine have focused on the impact of this drug on behavior and cognitive effects during early childhood. Prenatal methamphetamine produces a variety of neurological effects, including structural changes in the brain (8, 37), increased prevalence of cognitive and behavioral problems (11, 23), delayed development of gross motor skills (42), and decreased verbal and spatial memory (8). In contrast to these neurological effects, the impact of prenatal methamphetamin...

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Section: Discussionmentioning

confidence: 99%

Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts

Rorabaugh

Seeley

Bui

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…The low dose may have been insufficient to produce this change. High doses of cocaine may produce relatively greater impairment of uterine blood flow, greater hypoxia and malnutrition than lower doses would (Patel et al 1999). Also, it is unlikely that persistently high fetal levels of cocaine resulted in the development of tolerance since cocaine clears from the fetal circulation within a few hours (Dow-Edwards 1990).…”

Section: Discussionmentioning

confidence: 99%

The effects of prenatal cocaine, post-weaning housing and sex on conditioned place preference in adolescent rats

et al. 2014

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Rationale Gestational exposure to cocaine now affects several million people including adolescents and young adults. Whether prenatal drug exposures alter an individual's tendency to take and/or abuse drugs is still a matter of debate. Objectives This study sought to answer the question does prenatal exposure to cocaine, in a dose-response fashion, alter the rewarding effects of cocaine using a conditioned place preference (CPP) procedure during adolescence in the rat. Further, we wanted to assess possible sex differences and the role of being raised in an enriched vs impoverished environment. Methods Virgin female Sprague-Dawley rats were dosed daily with cocaine at 30mg/kg (C30), 60mg/kg (C60) or vehicle intragastrically prior to mating and throughout gestation. Pups were culled, fostered and on postnatal day (PND) 23 placed into isolation cages or enriched cages with 3 same-sex littermates and stimulus objects. On PND43-47, CPP was determined across a range of cocaine doses. Results C30 exposure increased sensitivity to the rewarding effects of cocaine in adolescent males and being raised in an enriched environment further enhanced this effect. Rats exposed to C60 resembled the controls in cocaine CPP. Overall, females were modestly affected by prenatal cocaine and enrichment. Conclusions These data support the unique sensitivity of males to the effects of gestational cocaine, that moderate prenatal cocaine doses produce greater effects on developing reward circuits than high doses, and that housing condition interacts with prenatal treatment and sex such that enrichment increases cocaine CPP most in adolescent males prenatally exposed to moderate cocaine doses.

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“…17 Patel and colleagues demonstrated in a rat model that a gastric cocaine dose of 60 mg/kg decreased uterine blood flow by 27% and placental blood flow by 30%. 18 When placentas from healthy women following normal vaginal delivery were incubated in 0, 30, 300 or 3000 ng/mL preparations of cocaine, there was an increase in the placental production of thromboxane and a decrease in the production of prostacyclin, leading to placental vasoconstriction. 19 The use of cocaine in the presence of impaired uteroplacental perfusion as found in diabetes or preeclampsia is of particular concern.…”

Section: Discussionmentioning

confidence: 99%

Topical vasoconstrictor use for nasal intubation during pregnancy complicated by cardiomyopathy and preeclampsia

Arendt

Khan

Curry

et al. 2011

International Journal of Obstetric Anesthesia

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Cocaine Decreases Uteroplacental Blood Flow in the Rat

Cited by 19 publications

References 21 publications

Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts

Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts

The effects of prenatal cocaine, post-weaning housing and sex on conditioned place preference in adolescent rats

Topical vasoconstrictor use for nasal intubation during pregnancy complicated by cardiomyopathy and preeclampsia

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