Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium‐derived hyperpolarizing factor (EDHF)

Gerber, Robert; Anwar, Muhammad; Poston, Lucilla

doi:10.1038/sj.bjp.0702099

Cited by 92 publications

(102 citation statements)

References 33 publications

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“…3,6,9 Similarly in pregnant rats, vasorelaxation is suggested as being mediated primarily through a combination of NO-and EDHF-mediated pathways. 25 Results from the present study demonstrated a significant contribution of NO, EDHF, and PGI 2 to vasorelaxation (induced by either BK or ACh) in normal plasma-treated vessels. In contrast, the residual relaxation after treatment with RUPP plasma appeared to be mediated via pathways independent of NO.…”

Section: Discussionsupporting

confidence: 51%

Plasma-Mediated Vascular Dysfunction in the Reduced Uterine Perfusion Pressure Model of Preeclampsia

et al. 2009

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Abstract-Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (PϽ0.001 The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N -nitro-L-arginine methyl ester (acetylcholine: 57Ϯ7 versus 63Ϯ7%, ns; bradykinin: 37Ϯ5 versus 35Ϯ5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels. Key Words: preeclampsia Ⅲ reduced uterine perfusion pressure Ⅲ endothelium Ⅲ hypertension Ⅲ plasma Ⅲ nitric oxide P reeclampsia (PE) is a multisystemic disorder of pregnancy which affects more than 8 million pregnancies worldwide annually. 1 The underlying etiology is incompletely understood, but current thinking suggests the development of a relatively hypoperfused placenta stimulates the maternal response, including alterations in the maternal vascular endothelium. 2 Impaired endothelium-dependent responses have been reported in systemic vessels isolated from women with PE. 3,4 Moreover, numerous studies have demonstrated disparities in terms of the relative contributions of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin (PGI 2 ) to vasodilatation in both physiological 5-8 and pathophysiological pregnancies. 3,6,9 In addition, the vascular dysfunction associated with PE has been shown to be induced by one or more circulating mediators as impaired relaxation was detected in resistance vessels exposed to plasma from women with PE. 10,11 Several animal models of pregnancy-induced hypertension (PIH) exist including the reduced uterine perfusion pressure (RUPP) rat, which involves the chronic reduction of uteroplacental perfusion resulting in a pregnancy-dependent hypertensive state. 12,13 Although a number of gene knockout models of PIH (Comt Ϫ/Ϫ 14 and BPH/5 15 mice) have emerged, those using chronic reduction of uteroplacental perfusion are still largely considered to be more sympathetic to the human condition as they are characterized by hypertension, reduced glomerular filtration rate, proteinuria, intrauterine growth restriction, and endothelial dysfunction. 13 Although PE is a complex con...

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Section: Discussionsupporting

confidence: 51%

Plasma-Mediated Vascular Dysfunction in the Reduced Uterine Perfusion Pressure Model of Preeclampsia

et al. 2009

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“…More recently, a role for EDHF in the increased endothelium-dependent relaxation during pregnancy has been gradually recognized. Thus several studies demonstrated that EDHF-type responses to several endothelium-dependent agonists might be increased in rat (15) or human resistance arteries in normal pregnancy (26,37). Our results indeed further strengthen the importance of EDHF to endothelium-dependent dilatation.…”

Section: Relative Contribution Of No Pgi 2 and Edhf To Bk-induced mentioning

confidence: 99%

The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women

Luksha¹,

Nisell²,

Kublickiene³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Luksha, Leonid, Henry Nisell, and Karolina Kublickiene. The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women. Am J Physiol Regul Integr Comp Physiol 286: R1102-R1109, 2004. First published January 29, 2004 10.1152/ajpregu.00550.2003.-We studied the importance of endothelium-derived hyperpolarizing factor (EDHF) vs. nitric oxide (NO) and prostacyclin (PGI2) in bradykinin (BK)-induced relaxation in isolated small subcutaneous arteries from normal pregnant women. We also explored the contribution of cytochrome P-450 (CYP450) product of arachidonic acid (AA) metabolism, hydrogen peroxide (H2O2), and gap junctions that have been suggested to be involved in EDHF-mediated responses. Isolated arteries obtained from subcutaneous fat biopsies of normal pregnant women (n ϭ 30) undergoing planned cesarean section were mounted in a wire-myography system. In norepinephrine-constricted vessels, incubation with N G -nitro-Larginine methyl ester (L-NAME) resulted in a significant reduction in relaxation to BK. Simultaneous incubation with L-NAME and indomethacin failed to modify this response further. BK-mediated dilatation in the presence of K ϩ -modified solution was decreased to similar level as obtained after incubation with L-NAME. Incubation with L-NAME abolished BK-induced responses in K ϩ -modified solution. Sulfaphenazole, a specific inhibitor of CYP450 epoxygenase, and catalase (an enzyme that decomposes H2O2) did not affect the EDHFmediated relaxation because concentration-response curves to BK were similar in arteries after incubation with L-NAME vs. L-NAME ϩ sulfaphenazole and L-NAME ϩ catalase. The inhibitor of gap junctions, 18␣-glycyrrhetinic acid, significantly reduced BK-mediated relaxation both without and with incubation with L-NAME. We found that both NO and EDHF, but not PGI2, are involved in the endothelium-dependent dilatation to BK. BK-induced relaxation is almost equally mediated by NO and EDHF. CYP450 epoxygenase metabolites of AA or H2O2 do not account for EDHF-mediated response; however, gap junctions are involved in the EDHF-mediated responses to BK in subcutaneous small arteries in normal pregnancy. endothelium-dependent relaxation; gap junctions; endothelium-derived hyperpolarizing factor; hydrogen peroxide MATERNAL CARDIOVASCULAR ADAPTATION to normal pregnancy is associated with decreased peripheral vascular resistance that plays an important role for blood pressure reduction despite an increase in plasma volume and cardiac output. The vascular adaptation to normal pregnancy is believed to be dependent on an enhanced endothelium-dependent dilatation (3,18,25). However, the pathways underlying these changes are not fully understood and need further investigation because an impaired cardiovascular adaptation is associated with the development of preeclampsia (18,25,42). It is generally accepted that preeclampsia is an endothelial cell disorder, and the increased vascular resistance and blood pressure during this pregnancyrelated disease are due to en...

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“…Results from two published reports indicated that the chronic estrogen elevations accompanying pregnancy were associated with increased release of a non-NO/non-prostanoid hyperpolarizing factor in mesenteric arteries (117) and aorta (118) when ACh was applied. On the other hand, in cerebral arteries, a seemingly opposite estrogen-related effect was observed.…”

Section: Regulation Of Endothelium-derived Hyperpolarizing Factor In mentioning

confidence: 99%

Estrogen and Cerebrovascular Physiology and Pathophysiology

Pelligrino

Galea

2001

Japanese Journal of Pharmacology

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ABSTRACT-Numerous studies have uncovered a wide variety of estrogen effects with apparent cardiovascular benefits, the most recognized ones being vasodilation, anti-atherogenesis, diminished post-ischemic inflammation and anti-oxidant effects. This article provides an overview of the influence of estrogen on the cerebral vasculature, under physiologic and pathophysiologic conditions, and covers both acute and chronic effects. The discussion is primarily focused on the vasodilatory and anti-inflammatory actions of estrogen, since those particular estrogen influences have received the greatest attention in studies published to date. With respect to vasodilation, although some consideration is given to the role of other vasodilating mechanisms and factors, the emphasis is mostly placed on the endothelial isoform of nitric oxide synthase, eNOS, which has emerged as a clear target of estrogen. Some consideration is given to recent findings that suggest that estrogen can stimulate eNOS activity by decreasing the expression of the eNOS inhibitor caveolin-1. With regard to the ability of estrogen to counteract inflammation, potential mechanisms by which estrogen limits the post-ischemic leukocyte adhesion, and the expression of the inducible NOS, are discussed.

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Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium‐derived hyperpolarizing factor (EDHF)

Cited by 92 publications

References 33 publications

Plasma-Mediated Vascular Dysfunction in the Reduced Uterine Perfusion Pressure Model of Preeclampsia

Plasma-Mediated Vascular Dysfunction in the Reduced Uterine Perfusion Pressure Model of Preeclampsia

The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women

Estrogen and Cerebrovascular Physiology and Pathophysiology

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