Dexamethasone Alters Vascular Reactivity by Enhancing COX-Related Vasodilatation in Fetal Ovine Carotids

Angeles, Danilyn M.; Chang, Melody; Leong, Valerie; Oberg, Kerby C.; Pearce, William J.

doi:10.1159/000090340

Cited by 5 publications

(2 citation statements)

References 54 publications

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“…al. has demonstrated that attenuation of 5-hydroxytryptamine-induced constrictions in fetal carotid arteries incubated with dexamethasone can be reversed with Indo, suggesting that there is increased contribution of COX products in the modulation of carotid artery reactivity after exposure to dexamethasone (23). …”

Section: Discussionmentioning

confidence: 99%

Antenatal Betamethasone Alters Vascular Reactivity in Adult Female Ovine Cerebral Arteries

et al. 2010

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Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K+-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta-exposed and control sheep whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there appeared to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep.

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Section: Discussionmentioning

confidence: 99%

Antenatal Betamethasone Alters Vascular Reactivity in Adult Female Ovine Cerebral Arteries

et al. 2010

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“…For serotonin, ERK activation appeared as a significant downstream component of 5HT receptor activation, particularly in fetal arteries [85]. Incubation with dexamethasone also exhibited a time-dependent ability to attenuate 5HT-induced contractions through a cyclooxygenase-dependent pathway in fetal arteries [86]. Conversely, incubation with dopamine enhanced contractile responses to 5HT [87], suggesting that vasoactive compounds commonly administered to neonates in the NICU may have conflicting effects on cerebrovascular contractility.…”

Section: The 2000s: Calcium Cgmp Pkc and Fetal Cbfmentioning

confidence: 99%

The Fetal Cerebral Circulation: Three Decades of Exploration by the LLU Center for Perinatal Biology

Pearce

2014

Advances in Fetal and Neonatal Physiology

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For more than three decades, research programs in the Center of Perinatal Biology have focused on the vascular biology of the fetal cerebral circulation. In the 1980s, research in the Center demonstrated that cerebral auto-regulation operated over a narrower pressure range, and was more vulnerable to insults, in fetuses than in adults. Other studies were among the first to establish that compared to adult cerebral arteries, fetal cerebral arteries were more hydrated, contained smaller smooth muscle cells and less connective tissue, and had endothelium less capable of producing NO. Work in the 1990s revealed that pregnancy depressed reactivity to NO in extra-cerebral arteries, but elevated it in cerebral arteries through effects involving changes in cGMP metabolism. Comparative studies verified that fetal lamb cerebral arteries were an excellent model for cerebral arteries from human infants. Biochemical studies demonstrated that cGMP metabolism was dramatically upregulated, but that contraction was far more dependent on calcium influx, in fetal compared to adult cerebral arteries. Further studies established that chronic hypoxia accelerates functional maturation of fetal cerebral arteries, as indicated by increased contractile responses to adrenergic agonists and perivascular adrenergic nerves. In the 2000s, studies of signal transduction established age-dependent roles for PKG, PKC, PKA, ERK, ODC, IP3, myofilament calcium sensitivity, and many other mechanisms. These diverse studies clearly demonstrated that fetal cerebral arteries were functionally quite distinct compared to adult cerebral arteries. In the current decade, research in the Center has expanded to a more molecular focus on epigenetic mechanisms and their role in fetal vascular adaptation to chronic hypoxia, maternal drug abuse, and nutrient deprivation. Overall, the past three decades have transformed thinking about, and understanding of, the fetal cerebral circulation due in no small part to the sustained research efforts by faculty and staff in the Center for Perinatal Biology.

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Design, synthesis and biological evaluation of dehydroabietic acid derivative as potent vasodilatory agents

Shen

et al. 2022

Bioorganic Chemistry

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Dexamethasone Alters Vascular Reactivity by Enhancing COX-Related Vasodilatation in Fetal Ovine Carotids

Cited by 5 publications

References 54 publications

Antenatal Betamethasone Alters Vascular Reactivity in Adult Female Ovine Cerebral Arteries

Antenatal Betamethasone Alters Vascular Reactivity in Adult Female Ovine Cerebral Arteries

The Fetal Cerebral Circulation: Three Decades of Exploration by the LLU Center for Perinatal Biology

Design, synthesis and biological evaluation of dehydroabietic acid derivative as potent vasodilatory agents

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