Consequences of maternal cocaine on cerebral microvascular functions in piglets

Yakubu, Momoh Audu; Pourcyrous, Massroor; Randolph, Mildred M.; Blaho, Kari; Mandrell, Timothy D.; Bada, Henrietta S.; Leffler, Charles W.

doi:10.1016/s0006-8993(02)02917-7

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…In contrast, norepinephrine-mediated contractions of aortas were not affected by the cocaine treatment, suggesting that fetal cocaine causes a tissue-selective programming of resistance vascular reactivity to the sympathetic neurotransmitter in adult offspring. Consistent with the present finding of altered agonist-mediated vascular contractions, Yakubu et al7 have reported that prenatal cocaine exposure significantly enhances 5-HT-, ET-1- and clonidine-induced constrictions of cerebral arterioles in neonate piglets.…”

Section: Discussionsupporting

confidence: 92%

“…Recently, we have demonstrated in a rat model that fetal exposure to cocaine during gestation results in an increase in heart susceptibility to ischemia and reperfusion injury in adult male offspring 6. Additionally, other studies have demonstrated that prenatal cocaine exposure results in an attenuated vasodilation and enhanced responses to vasoconstrictors in cerebral arteries in the neonate 7,8…”

Section: Introductionmentioning

confidence: 99%

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Prenatal Cocaine Exposure Differentially Causes Vascular Dysfunction in Adult Offspring

Xiao

Huang

et al. 2009

Hypertension

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Abstract-Epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of cardiovascular diseases and hypertension in adult life. The present study tested the hypothesis that prenatal cocaine exposure causes reprogramming of vascular reactivity, leading to an increased risk of hypertension in adult offspring. Pregnant rats received cocaine (30 mg kg Ϫ1 day Ϫ1) or saline from days 15 to 21 of gestational age, and experiments were conducted in 3-month-old offspring. Cocaine had no effect on the baseline blood pressure but significantly increased norepinephrine-stimulated blood pressure and decreased the baroreflex sensitivity in male but not female offspring. The cocaine treatment significantly increased norepinephrine-induced contractions in pressurized resistance-sized mesenteric arteries but not in aortas, which was primarily because of a loss of endothelial NO synthase-mediated inhibition and an enhanced Ca 2ϩ sensitivity in mesenteric arteries. In addition, the cocaine treatment significantly attenuated the endothelium-dependent relaxation in mesenteric arteries in male but not female offspring. Endothelial NO synthase protein levels in aortas but not mesenteric arteries were significantly increased in the cocaine-treated animals. However, cocaine significantly decreased phosphorylation levels of endothelial NO synthase in both aortas and mesenteric arteries. The results suggest that prenatal cocaine exposure programs vascular contractility via changes in endothelial NO synthase-regulated Ca 2ϩ sensitivity of myofilaments in the sex-and tissue-dependent manners in resistance arteries leading to an increased risk of hypertension in male offspring. [1][2][3][4] In utero exposure to cocaine is a significant public health problem. Offspring born to mothers with a history of cocaine abuse have a high incidence of congenital cardiovascular malformations. 5 Recently, we have demonstrated in a rat model that fetal exposure to cocaine during gestation results in an increase in heart susceptibility to ischemia and reperfusion injury in adult male offspring. 6 In addition, other studies have demonstrated that prenatal cocaine exposure results in an attenuated vasodilation and enhanced responses to vasoconstrictors in cerebral arteries in the neonate. 7,8 It is unknown whether or to what extent fetal cocaine exposure affects the vascular reactivity of resistance vessels in adult offspring. Given the importance of resistance arteries in the regulation of blood pressure (BP), dysfunction of resistance arteries is likely to contribute to the development of hypertension observed frequently in adult offspring who experienced an adverse intrauterine environment before birth. 9,10 To investigate the fetal programming of cardiovascular function in response to fetal cocaine exposure, the present study was designed to test the hypothesis that maternal cocaine administration during pregnancy causes reprogramming of vascular reactivity leading to an increased risk of hypertension...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Prenatal Cocaine Exposure Differentially Causes Vascular Dysfunction in Adult Offspring

Xiao

Huang

et al. 2009

Hypertension

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“…Yakubu et at. (23) observed increased cerebral vasoconstrictive responses to endothelin-l in cocaine-exposed piglets compared to nonexposed. We found enhanced cerebrovascular constriction in response to norepinephrine in cocaine-exposed piglets.…”

Section: Discussionmentioning

confidence: 67%

Chronic Prenatal Exposure to Cocaine Alters Cerebrovascular Responses in Newborn Pigs

Pourcyrous

Bada

Blaho

et al. 2004

Exp Biol Med (Maywood)

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Maternal cocaine abuse may increase the incidence of perinatal asphyxia. In nonexposed asphyxiated neonates, decreased cerebrospinal fluid (CSF) cAMP concentrations are associated with poor neurological outcome. On the other hand, cocaine increases central nervous system (CNS) cAMP. Therefore, we hypothesized that in utero cocaine exposure may increase brain cAMP and thereby preserve cerebrovascular responses to cAMP-dependent stimuli following asphyxia. Pregnant pigs received either cocaine (1 mg/kg, i.v.) twice weekly during the last trimester or normal saline vehicle (sham-control) and were allowed to deliver vaginally at term. Cranial windows were implanted in the newborn pigs within the first week of life and used to collect CSF for cAMP determinations and to assess changes in pial arteriolar diameters (PAD). In the first part of the study, pial arteriolar responses to different vasodilator and vasoconstrictor stimuli were evaluated in piglets prior to asphyxia (n = 20). In newborn pigs exposed to cocaine, cerebrovascular responses to hypercapnia and norepinephrine were significantly exaggerated compared to controls. Then, piglets were randomly selected for the second part of the study that involved prolonged asphyxia (n = 12). In cocaine-exposed but not sham-control piglets, CSF cAMP increased markedly during asphyxia. In the sham piglets, but not the cocaine-exposed piglets, CSF cAMP fell progressively below the baseline during recovery. Cerebrovascular reactivity to cAMP-dependent stimuli (hypercapnia and isoproterenol) was preserved during recovery from asphyxia in the cocaine-exposed piglets but significantly attenuated in the sham controls. We conclude that piglets with chronic prenatal exposure to cocaine show exaggerated cerebrovascular responses to vasogenic stimuli and preserved cAMP-dependent cerebral vasoreactivity following asphyxia.

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“…The ability of prenatal cocaine to alter vascular function is not unique to rodents. Potentiation of norepinephrine-, endothelin-, and serotonin-induced vasoconstriction have been reported in the cerebral vasculature of piglets that were prenatally exposed to cocaine (37,38). These studies provide evidence that prenatal exposure to cocaine can have long term effects on the vasculature that may increase the risk of developing hypertension or other vascular disorders later in life.…”

Section: Impact Of Prenatal Exposure To Cns Stimulants On the Adult Cmentioning

confidence: 61%

Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?

Rorabaugh

2021

Front. Cardiovasc. Med.

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Prenatal exposure to an adverse uterine environment can have long lasting effects on adult offspring through DNA methylation, histone acetylation, and other epigenetic effects that alter gene expression and physiology. It is well-known that consumption of CNS stimulants such as caffeine, nicotine, amphetamines, and cocaine during pregnancy can adversely impact the offspring. However, most work in this area has focused on neurological and behavioral outcomes and has been limited to assessments in young offspring. The impact of prenatal exposure to these agents on the adult cardiovascular system has received relatively little attention. Evidence from both animal and human studies indicate that exposure to CNS stimulants during the gestational period can negatively impact the adult heart and vasculature, potentially leading to cardiovascular diseases later in life. This review discusses our current understanding of the impact of prenatal exposure to cocaine, methamphetamine, nicotine, and caffeine on the adult cardiovascular system.

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Consequences of maternal cocaine on cerebral microvascular functions in piglets

Cited by 6 publications

References 27 publications

Prenatal Cocaine Exposure Differentially Causes Vascular Dysfunction in Adult Offspring

Prenatal Cocaine Exposure Differentially Causes Vascular Dysfunction in Adult Offspring

Chronic Prenatal Exposure to Cocaine Alters Cerebrovascular Responses in Newborn Pigs

Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?

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