Resistance Artery Adaptation to Pregnancy Counteracts the Vasoconstricting Influence of Plasma From Normal Pregnant Women

Amburgey, Ödül A.; Reeves, Shane; Bernstein, Ira M.; Cipolla, Marilyn J.

doi:10.1177/1933719109345288

Cited by 14 publications

(17 citation statements)

References 45 publications

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“…In addition, CE+HTN serum caused the greatest vasoconstriction and the highest amount of tone, with a significant difference compared to LVD+HTN group. MAs had significantly lower tone than PCAs in all groups, as shown previously [26]. However, the presence of both LVD and CE+HTN serum caused an increase in tone in MAs compared to control PSS and LVD+HTN serum.…”

Section: Resultssupporting

confidence: 87%

Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function

Canavero

Sherburne

Tremble

et al. 2016

Transl. Stroke Res.

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We investigated the effects of circulating factors in serum obtained from patients in the acute phase of different subtypes of ischemic stroke on non-ischemic cerebral and mesenteric arteries, as a potential mechanism involved in influencing regional perfusion and thus clinical evolution. Posterior cerebral arteries (PCAs) and mesentery arteries (MAs) isolated from Wistar Kyoto rats were perfused with serum from acute stroke patients with large vessel disease without (LVD) or with hypertension (LVD+HTN), cardioembolism with hypertension (CE+HTN) or physiologic saline as controls. Myogenic activity and nitric oxide-dependent vasorelaxation were assessed after 2 hours of intraluminal exposure to serum. Vascular function was differentially affected by sera. Exposure to LVD serum increased myogenic tone and produced endothelial dysfunction in both PCAs and MAs. However, CE+HTN serum increased tone and decreased smooth muscle sensitivity to NO in vessels from both vascular beds. LVD+HTN serum was associated with reduced smooth muscle sensitivity to NO in vessels from both vascular beds but increased tone only in PCAs. Inflammation and oxidative stress, determined by measurement of high sensitivity C-reactive protein, uric acid and free 8-isoprostane, were enhanced in all the serum groups. These results demonstrate vasoactive properties of acute stroke serum related to stroke subtypes that could potentially contribute to the pathogenesis of early hemodynamic-based clinical events.

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Section: Resultssupporting

confidence: 87%

Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function

Canavero

Sherburne

Tremble

et al. 2016

Transl. Stroke Res.

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“…The influence of EDHF in PCAs perfused with normal pregnant or preeclamptic plasma was assessed by measuring vasodilation to the addition of A23187 in the presence of NOS and COX inhibition (Figure 6). This is a common approach for assessing EDHF-related mechanisms17. Under these conditions, A23187 caused dilation in all vessels that was not different between groups.…”

Section: Resultsmentioning

confidence: 97%

“…It has been hypothesized that circulating factors in preeclampsia contribute to the development of brain edema and the neurological complications of severe preeclampsia 17–19. However, an effect of preeclamptic plasma on BBB permeability has not been previously examined.…”

Section: Discussionmentioning

confidence: 99%

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Plasma From Preeclamptic Women Increases Blood-Brain Barrier Permeability

et al. 2010

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Abstract-Circulating factors in preeclamptic women are thought to cause endothelial dysfunction and thereby contribute to the progression of this hypertensive condition. Despite the involvement of neurological complications in preeclampsia, there is a paucity of data regarding the effect of circulating factors on cerebrovascular function. Using a rat model of pregnancy, we investigated blood-brain barrier permeability, myogenic activity, and the influence of endothelial vasodilator mechanisms in cerebral vessels exposed intraluminally to plasma from normal pregnant or preeclamptic women. In addition, the role of vascular endothelial growth factor signaling in mediating changes in permeability in response to plasma was investigated. A 3-hour exposure to 20% normal pregnant or preeclamptic plasma increased blood-brain barrier permeability by Ϸ6.5-and 18.0-fold, respectively, compared with no plasma exposure (PϽ0.01). Inhibition of vascular endothelial growth factor receptor kinase activity prevented the increase in permeability in response to preeclamptic plasma but had no effect on changes in permeability of vessels exposed to normal pregnant plasma. Circulating factors in preeclamptic plasma did not affect myogenic activity or the influence of endothelium on vascular tone. These findings demonstrate that acute exposure to preeclamptic plasma has little effect on reactivity of cerebral arteries but significantly increases blood-brain barrier permeability. Prevention of increased permeability by inhibition of vascular endothelial growth factor signaling suggests that activation of this pathway may be responsible for increased blood-brain barrier permeability after exposure to preeclamptic plasma. (Hypertension. 2010;56:1003-1008.)Key Words: circulating factors Ⅲ plasma Ⅲ preeclampsia Ⅲ blood-brain barrier Ⅲ permeability Ⅲ vascular endothelial growth factor P reeclampsia affects 3% to 8% of all pregnancies and represents a major cause of maternal and perinatal morbidity. 1 Although the pathophysiology behind the development of preeclampsia remains elusive and highly debated, one theory is that abnormal remodeling of uteroplacental bed spiral arteries leads to placental hypoperfusion, prompting release of factors into the maternal circulation. 2-4 These circulating factors include angiogenic and antiangiogenic molecules like soluble fms-like tyrosine kinase 1 receptor (sflt-1) and select cytokines. 3,5 For example, sflt-1, the soluble receptor for vascular endothelial growth factor (VEGF) receptor (VEGFR) 1, is elevated in preeclamptic plasma and has been shown to inhibit certain actions of VEGF. 3,5 In this manner, sflt-1 is thought to provoke endothelial dysfunction resulting in decreased endotheliumdependent vasodilation and increased vessel reactivity. Such changes may increase total peripheral vascular resistance, contributing to a major feature of preeclampsia, namely, hypertension. [2][3][4] One of the most serious sequelae of preeclampsia are eclamptic seizures, a leading cause of maternal and fetal morbidit...

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“…This may be due to either development of resistance to vasoconstrictors circulating during pregnancy or increased sensitivity to vasodilators also circulating in pregnancy. Interestingly, this finding was specific to the cerebral vasculature, since the effect of pregnant plasma was not seen in mesenteric arteries (3). Thus the adaptation of the cerebral circulation during pregnancy is unique compared with the adaptation of other organ systems.…”

Section: Vasomotor Responses To Circulating Factorsmentioning

confidence: 92%

The Cerebral Circulation During Pregnancy: Adapting to Preserve Normalcy

Johnson

Cipolla

2015

Physiology

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The adaptation of the brain and cerebral circulation to pregnancy are unique compared with other organs and circulatory systems, ultimately functioning to maintain brain homeostasis. In this review, the effect of pregnancy on critical functions of the cerebral circulation is discussed, including changes occurring at the endothelium and blood-brain barrier, and changes in the structure and function of cerebral arteries and arterioles, hemodynamics, and cerebral blood flow autoregulation. The brain is an organ of high metabolic demand that consumes ϳ20% of the body's oxygen at rest, despite comprising only 2% of body weight (77). Importantly, the brain has a relatively narrow capacity to tolerate changes in ion and water balance, and blood flow (77). The brain is also unique in that it is enclosed in a rigid skull, and therefore increased vascular permeability or volume could result in detrimentally increased intracranial pressure that can cause serious neurological symptoms, brain herniation, and even death. Thus there is a need to maintain tight control of cerebral blood flow (CBF) and water flux in the face of a 40 -50% increase in plasma volume and cardiac output during pregnancy and a decline in systemic vascular resistance necessary for the maintenance of a healthy blood pressure (28). In contrast to other organs outside the central nervous system that undergo substantial increases in both perfusion and transvascular filtration during pregnancy, including the uterus, kidney, and heart, the cerebral circulation must resist these adaptations to counterbalance global hemodynamic changes to maintain the delicate microenvironment of the brain. Thus the adaptation of the brain and cerebral circulation to pregnancy appears to be to maintain normalcy despite substantial hormonal and cardiovascular changes in almost every other organ. Throughout this review, the effect of pregnancy on several aspects of the cerebral circulation will be discussed, including the cerebral endothelium and blood-brain barrier (BBB), the structure and function of the cerebrovasculature, hemodynamics, and CBF autoregulation. Furthermore, in the context of these cerebrovascular adaptations, the risk for neurological complications that arises in women with preeclampsia, a dangerous hypertensive complication of pregnancy, will be considered. Preeclampsia affects 3-8% of all pregnancies and is defined as the appearance of hypertension and proteinuria after week 20 of gestation. Many organs are affected by preeclampsia, including the brain, putting women at risk of seizure and hemorrhage. In fact, the cerebral circulation has a central role in neurological complications of preeclampsia, and thus understanding how pregnancy and preeclampsia affect the cerebrovasculature is of interest. Vasomotor Responses to Circulating FactorsOne of the most important adaptations of the cerebral circulation during pregnancy is to counteract the effects of circulating vasoactive factors. During pregnancy, large amounts of hormones are secreted from the placenta, ...

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Resistance Artery Adaptation to Pregnancy Counteracts the Vasoconstricting Influence of Plasma From Normal Pregnant Women

Cited by 14 publications

References 45 publications

Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function

Effects of Acute Stroke Serum on Non-Ischemic Cerebral and Mesenteric Vascular Function

Plasma From Preeclamptic Women Increases Blood-Brain Barrier Permeability

The Cerebral Circulation During Pregnancy: Adapting to Preserve Normalcy

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