β-Adrenoceptor Subtype Expression in Human Placenta and Umbilical Arteries in Normal and Preeclamptic Pregnancies

Hynes, Paul G.; Friel, Anne M.; Smith, Terry J.

doi:10.1080/10641950701826554

Cited by 13 publications

(21 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the vascular responses during pregnancy may not be uniform and may vary depending on the vascular bed studied and the vessel size down the arterial tree, i.e., large, intermediate, small, and microvessels. The differences in the responses of various blood vessels can be related to differences in vasoconstrictor receptor distribution, receptor-coupling mechanisms, and postreceptor mechanisms particularly [Ca 2ϩ ] i control mechanisms and [Ca 2ϩ ] i sensitization path-ways (7,31,45). Previous studies (6) have shown that the mesenteric vascular resistance is elevated in rat models of HTN-Preg.…”

mentioning

confidence: 99%

Differential [Ca²⁺]_i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Chen¹,

Khalil²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Chen W, Khalil RA. Differential [Ca 2ϩ ]i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats. Am J Physiol Regul Integr Comp Physiol 295: R1962-R1972, 2008. First published October 8, 2008 doi:10.1152/ajpregu.90523.2008.-Vascular resistance and blood pressure (BP) are reduced during late normal pregnancy (Norm-Preg). In contrast, studies in human preeclampsia and in animal models of hypertension in pregnancy (HTN-Preg) have suggested that localized reduction in uterine perfusion pressure (RUPP) in late pregnancy is associated with increased systemic vascular resistance and BP; however, the vascular mechanisms involved are unclear. Because Ca 2ϩ is a major determinant of vascular contraction, we hypothesized that the intracellular free calcium concentration ([Ca 2ϩ ]i) signaling of vasoconstriction is differentially regulated in systemic microvessels during normal and RUPP in late pregnancy. Pressurized mesenteric microvessels from Norm-Preg and RUPP rats were loaded with fura 2 in preparation for simultaneous measurement of diameter and ]i in Norm-Preg (45.5 Ϯ 3.3 and 0.89 Ϯ 0.02%) and RUPP rats (46.3 Ϯ 2.1 and 0.87 Ϯ 0.01%). Maximum vasoconstriction to Phe, ANG II, and ET-1 was not significantly different between Norm-Preg (28.6 Ϯ 4.8, 32.5 Ϯ 6.3, and 40 Ϯ 4.6%, respectively) and RUPP rats (27.8 Ϯ 5.9, 34.4 Ϯ 4.3, and 38.8 Ϯ 4.1%, respectively). In contrast, the initial Phe-, ANG II-, and ET-1-induced 340/380 ratio ([Ca 2ϩ ]i) was reduced in RUPP (0.83 Ϯ 0.02, 0.82 Ϯ 0.02, and 0.83 Ϯ 0.03, respectively) compared with Norm-Preg rats (0.95 Ϯ 0.04, 0.93 Ϯ 0.01, and 0.92 Ϯ 0.02, respectively). Also, the [Ca 2ϩ ]i-vasoconstriction relationship was similar in KCl-treated but shifted to the left in Phe-, ANG II-, and ET-1-treated microvessels of RUPP compared with Norm-Preg rats. The lower agonist-induced [Ca 2ϩ ]i signal of vasoconstriction and the leftward shift in the [Ca 2ϩ ]i-vasoconstriction relationship in microvessels of RUPP compared with Norm-Preg rats suggest activation of [Ca 2ϩ ]i sensitization pathway(s). The similarity in vasoconstriction in RUPP and Norm-Preg rats suggests that such a [Ca 2ϩ ]i sensitization pathway(s) may also provide a feedback effect on Ca 2ϩ mobilization/homeostatic mechanisms to protect against excessive vasoconstriction in systemic microvessels during RUPP in late pregnancy. resistance vessels; vascular smooth muscle; intracellular free calcium concentration; preeclampsia DURING NORMAL PREGNANCY (Norm-Preg) increases in plasma volume, heart rate, and renal blood flow, as well as decreases in systemic vascular resistance, blood pressure (BP), and vascular reactivity to circulating vasoconstrictors are often observed (8,18,37,65). In contrast, in 5-7% of pregnancy, women develop a condition called preeclampsia, which is characterized by increased intravascular coagulation, proteinuria, increased systemic vascular resistance, and hypertension in pregnancy Refs. 24,25,32,59,60,63,66). Although HTN-Preg is ...

show abstract

mentioning

confidence: 99%

Differential [Ca²⁺]_i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Chen¹,

Khalil²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…In preeclampsia, a hypertensive gestational state, ß 2 -AR and ß 3 -AR protein levels in placentae were similar to those of normal patients, suggesting that aberrations in the ß-AR signaling, rather than in the regulation of ß-AR-subtype expression, may occur in preeclampsia [34]. This hypothesis is supported by the fact that fenoterol-and BRL37344-induced relaxations were partly reduced due to the attenuation of cAMP levels, suggesting that ß 2 -and ß 3 -AR agonists may have considerable future pharmaceutical implications in the clinical management of pregnancyrelated disorders (eg, preterm labor) or other conditions (eg, intrauterine growth restrictions) in which improvement in fetoplacental exchanges may be of interest [33].…”

Section: Hypertensionmentioning

confidence: 85%

“…Nevertheless, it is important to note that the authors used endotheliumdenuded artery rings, whereas many studies performed in human and animal models suggest a preferential endothelial location of ß 3 -AR. Finally, ß 3 -AR also was described in human hepatic artery [31], and its presence was confirmed in umbilical and placental arteries [34]. Surprisingly, although nebivolol has been described as a ß 3 -AR agonist in human [12] and rat vessels [5], a recent study reports that nebivolol was not a ß 3 -AR agonist in rat and human urinary bladders [35].…”

Section: ß 3 -Adrenoceptors In Blood Vesselsmentioning

confidence: 99%

Beta-3 Adrenoceptors as New Therapeutic Targets for Cardiovascular Pathologies

Gauthier

Rozec

Manoury

et al. 2011

Curr Heart Fail Rep

View full text Add to dashboard Cite

Catecholamines play a key role in the regulation of cardiovascular function, classically through ß(1/2)-adrenoreceptors (AR) activation. After ß(3)-AR cloning in the late 1980s, convincing evidence for ß(3)-AR expression and function in cardiovascular tissues recently initiated a reexamination of their involvement in the pathophysiology of cardiovascular diseases. Their upregulation in diseased cardiovascular tissues and resistance to desensitization suggest they may be attractive therapeutic targets. They may substitute for inoperant ß(1/2)-AR to mediate vasodilation in diabetic or atherosclerotic vessels. In cardiac ventricle, their contractile effects are functionally antipathetic to those of ß(1/2)-AR; in normal heart, ß(3)-ARs may mediate a moderate negative inotropic effect, but in heart failure, it may protect against adverse effects of excessive catecholamine stimulation by action on excitation-contraction coupling, electrophysiology, or remodelling. Thus, prospective studies in animals and patients at different stages of heart failure should lead to identify the best therapeutic window to use ß(3)-AR agonists and/or antagonists.

show abstract

“…The roles played by β3-AR in embryonic development and fetal life remain poorly understood. However, studies report β3-AR expression in human and animal germ cells, where it induces motility ( 81 ), in pre-implantation embryos ( 82 , 83 ), during the first stages of embryogenesis ( 84 ), in embryo tissues, and in placenta ( 85 , 86 ). Moreover, β3-AR is upregulated in the human pregnant myometrium where inhibits spontaneous contractions and represents the predominant subtype over β2-AR ( 87 , 88 ).…”

Section: Introductionmentioning

confidence: 99%

β3-Adrenoceptors as Putative Regulator of Immune Tolerance in Cancer and Pregnancy

et al. 2020

View full text Add to dashboard Cite

Understanding the mechanisms of immune tolerance is currently one of the most important challenges of scientific research. Pregnancy affects the immune system balance, leading the host to tolerate embryo alloantigens. Previous reports demonstrated that β-adrenergic receptor (β-AR) signaling promotes immune tolerance by modulation of NK and Treg, mainly through the activation of β2-ARs, but recently we have demonstrated that also β3-ARs induce an immune-tolerant phenotype in mice bearing melanoma. In this report, we demonstrate that β3-ARs support host immune tolerance in the maternal microenvironment by modulating the same immune cells populations as recently demonstrated in cancer. Considering that β3-ARs are modulated by oxygen levels, we hypothesize that hypoxia, through the upregulation of β3-AR, promotes the biological shift toward a tolerant immunophenotype and that this is the same trick that embryo and cancer use to create an aura of immune-tolerance in a competent immune environment. This study confirms the analogies between fetal development and tumor progression and suggests that the expression of β3-ARs represents one of the strategies to induce fetal and tumor immune tolerance.

show abstract

β-Adrenoceptor Subtype Expression in Human Placenta and Umbilical Arteries in Normal and Preeclamptic Pregnancies

Abstract: Aberrations in the beta-adrenoceptor signalling systems, rather than in the regulation of expression of these receptors may occur in preeclampsia, as is the case in other hypertensive disorders.

Cited by 13 publications

References 18 publications

Differential [Ca²⁺]_i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Differential [Ca²⁺]_i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Beta-3 Adrenoceptors as New Therapeutic Targets for Cardiovascular Pathologies

β3-Adrenoceptors as Putative Regulator of Immune Tolerance in Cancer and Pregnancy

Contact Info

Product

Resources

About

β-Adrenoceptor Subtype Expression in Human Placenta and Umbilical Arteries in Normal and Preeclamptic Pregnancies

Abstract: Aberrations in the beta-adrenoceptor signalling systems, rather than in the regulation of expression of these receptors may occur in preeclampsia, as is the case in other hypertensive disorders.

Cited by 13 publications

References 18 publications

Differential [Ca2+]i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Differential [Ca2+]i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Beta-3 Adrenoceptors as New Therapeutic Targets for Cardiovascular Pathologies

β3-Adrenoceptors as Putative Regulator of Immune Tolerance in Cancer and Pregnancy

Contact Info

Product

Resources

About

Differential [Ca²⁺]_i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats

Differential [Ca²⁺]_i signaling of vasoconstriction in mesenteric microvessels of normal and reduced uterine perfusion pregnant rats