Prenatal Exposure to Methamphetamine Causes Vascular Dysfunction in Adult Male Rat Offspring

Chavva, Hasitha; Belcher, Adam M.; Brazeau, Daniel A.; Rorabaugh, Boyd R.

doi:10.3389/fcvm.2022.830983

Cited by 3 publications

(4 citation statements)

References 63 publications

(89 reference statements)

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“…However, comparison of methamphetamine induced changes during the prenatal period and during early adulthood revealed no similarities in the identity of the genes that were changed. Notably, 5 of the top 6 changes in gene expression (in terms of the magnitude of the changes) in hearts from females that were exposed to methamphetamine as adults involved genes that regulate the circadian clock ( Dbp, Per2, Per3, Arntl , and Npas2 ) (Chavva et al, 2022 ). These genes were not altered in hearts of adult rats following prenatal exposure to methamphetamine.…”

Section: Discussionmentioning

confidence: 99%

“…We recently reported that chronic fetal exposure to methamphetamine leads to vascular dysfunction in adult offspring. Adult (5 months old) rats that were exposed to methamphetamine throughout the gestational period exhibited vascular dysfunction characterized by potentiation of angiotensin II‐induced vasoconstriction and attenuation of perivascular adipose tissue (PVAT)‐dependent relaxation (Chavva et al, 2022 ). In contrast to the effects of prenatal methamphetamine on the ischemic heart (Rorabaugh et al, 2016 ), the effects of prenatal methamphetamine on vascular function occurred exclusively in male offspring.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, few studies have investigated the impact of prenatal exposure to methamphetamine on adult cardiovascular function. We recently reported that prenatal exposure to methamphetamine induces sex‐dependent changes in the cardiovascular system that extend into adulthood (Chavva et al, 2022 ). Adult male rats (but not their female littermates) that were prenatally exposed to methamphetamine exhibit vascular dysfunction that is characterized by potentiation of angiotensin II‐induced contraction of the aorta, attenuation of acetylcholine‐induced relaxation, and alterations in the function of perivascular adipose tissue that plays an important role in regulating vascular tone (Chavva et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…We recently reported that prenatal exposure to methamphetamine induces sex‐dependent changes in the cardiovascular system that extend into adulthood (Chavva et al, 2022 ). Adult male rats (but not their female littermates) that were prenatally exposed to methamphetamine exhibit vascular dysfunction that is characterized by potentiation of angiotensin II‐induced contraction of the aorta, attenuation of acetylcholine‐induced relaxation, and alterations in the function of perivascular adipose tissue that plays an important role in regulating vascular tone (Chavva et al, 2022 ). We have also found that adult female rats (but not their male littermates) that were prenatally exposed to methamphetamine developed myocardial hypersensitivity to ischemic injury (Rorabaugh et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Maternal use of methamphetamine induces sex‐dependent changes in myocardial gene expression in adult offspring

Dague

Chavva

Brazeau

et al. 2022

Physiological Reports

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Methamphetamine is a commonly abused illicit stimulant that has prevalent use among women of child‐bearing age. While there are extensive studies on the neurological effects of prenatal methamphetamine exposure, relatively little is known about the effect of prenatal methamphetamine on the adult cardiovascular system. Earlier work demonstrated that prenatal methamphetamine exposure sex dependently (females only) sensitizes the adult heart to ischemic injury. These data suggest that prenatal exposure to methamphetamine may induce sex‐dependent changes in cardiac gene expression that persist in adult offspring. The goal of this study was to test the hypothesis that prenatal methamphetamine exposure induces changes in cardiac gene expression that persist in the adult heart. Hearts of prenatally exposed female offspring exhibited a greater number of changes in gene expression compared to male offspring (184 changes compared with 74 in male offspring and 89 changes common between both sexes). Dimethylarginine dimethylaminohydrolase 2 and 3‐hydroxybutyrate dehydrogenase 1 (genes implicated in heart failure) were shown by Western Blot to be under expressed in adult females that were prenatally exposed to methamphetamine, while males were deficient in 3‐Hydroxybutyrate Dehydrogenase 1 only. These data indicate that prenatal methamphetamine exposure induces changes in gene expression that persist into adulthood. This is consistent with previous findings that prenatal methamphetamine sex dependently sensitizes the adult heart to ischemic injury and may increase the risk of developing cardiac disorders during adulthood.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Maternal use of methamphetamine induces sex‐dependent changes in myocardial gene expression in adult offspring

Dague

Chavva

Brazeau

et al. 2022

Physiological Reports

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Maternal use of methamphetamine alters cardiovascular function in the adult offspring

Belcher

Rorabaugh

2023

Biochem. Cell Biol.

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Methamphetamine is one of the most commonly used illicit drugs during pregnancy. Most studies investigating the impact of maternal use of methamphetamine on children have focused on neurological outcomes. In contrast cardiovascular outcomes in these children have not been characterized. Recent studies in rodents provide evidence that prenatal exposure to methamphetamine induces changes in cardiac gene expression, changes in the heart’s susceptibility to ischemic injury, and changes in vascular function that may increase the risk of developing cardiovascular disorders later in life. Importantly, these changes are sex-dependent. This review summarizes our current understanding of how methamphetamine use during pregnancy impacts the cardiovascular function of adult offspring and highlight gaps in our knowledge of the potential cardiovascular risks associated with prenatal exposure to methamphetamine.

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Methamphetamine use during the first or second half of pregnancy worsens cardiac ischemic injury in adult female offspring

Chavva¹,

Rorabaugh

2022

Physiol Res

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There is growing evidence that methamphetamine use during pregnancy may produce detrimental cardiovascular effects in the adult offspring. Prior work demonstrated that chronic methamphetamine exposure throughout the gestational period causes adult female offspring to become hypersensitive to myocardial ischemic injury. The goal of the present study was to determine whether this methamphetamine-induced effect occurs early or late in the gestational period. Pregnant female rats were divided into 4 experimental groups. Groups 1 and 2 received subcutaneous injections of saline (group 1) or methamphetamine (5 mg/kg) (group 2) throughout the gestational period. Group 3 received methamphetamine injections on days 1-11 and saline on days 12-22, and group 4 received saline on days 1-11 and methamphetamine on days 12-22. Hearts were isolated from adult (8 weeks) female offspring and subjected to 30 min ischemia and 2 hours reperfusion on a Langendorff isolated heart apparatus. Contractile function was measured via an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Infarcts were significantly larger in methamphetamine exposed offspring regardless of whether they had been exposed to methamphetamine during the first half or the second half of the gestational period. Prenatal exposure to methamphetamine had no effect on preischemic contractile function or postischemic recovery of contractile function. These data indicate that methamphetamine use during either the first half or second half of pregnancy increases susceptibility to myocardial infarction in adult female offspring. These data provide further evidence that prenatal exposure to methamphetamine may increase the risk of developing cardiovascular diseases during adulthood.

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Prenatal Exposure to Methamphetamine Causes Vascular Dysfunction in Adult Male Rat Offspring

Cited by 3 publications

References 63 publications

Maternal use of methamphetamine induces sex‐dependent changes in myocardial gene expression in adult offspring

Maternal use of methamphetamine induces sex‐dependent changes in myocardial gene expression in adult offspring

Maternal use of methamphetamine alters cardiovascular function in the adult offspring

Methamphetamine use during the first or second half of pregnancy worsens cardiac ischemic injury in adult female offspring

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