The Role of Endogenous Endothelin in the Regulation of Uteroplacental and Renal Blood Flow During Pregnancy in Conscious Rats

Ajne, Gunilla; Nisell, Henry; Wolff, Kerstin; Jansson, Thomas

doi:10.1016/s0143-4004(03)00113-9

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…ET B antagonism during pregnancy results in vasoconstriction and decreased perfusion of the kidney. Ajne also reported decreased renal blood flow with administration of a mixed ET A /ET B antagonist as well as with L-NAME administration during pregnancy in the rat (30,35). In humans, Schmidt et al demonstrated that administration of a NOS inhibitor resulted in a significant reduction in renal plasma flow, and that co-administration of an ET A antagonist improved renal perfusion (36).…”

Section: Discussionmentioning

confidence: 93%

Impact of Endothelin A Receptor Antagonist Selectivity in Chronic Nitric Oxide Synthase Inhibition-Induced Fetal Growth Restriction in the Rat

Neerhof

Synowiec

Khan

et al. 2010

Hypertension in Pregnancy

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Objective Endothelin receptor A (ETA) antagonism improves fetal and placental growth and placental perfusion on days 1 and 4, but not day 7 of a 7-day infusion of a nitric oxide synthase (NOS) inhibitor. Our purpose was to evaluate the significance of the degree of ETA antagonist selectivity on uteroplacental perfusion and fetal growth on day 7 of chronic NOS inhibition. Methods Timed-pregnant rats were treated with the NOS inhibitor nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg/h) with and without one of the following ETA antagonists or their respective vehicles for 7 days beginning on day 14 of gestation: A-127722 (2,000-fold selective for ETA over ETB), FR139317 (8,000-fold ETA-selective), or ABT-546 (28,000-fold ETA-selective). Uterine and placental perfusion, as well as fetal and placental weight, was evaluated at the 7th day of treatment (gestation day 21). Results L-NAME administration resulted in a significant reduction in uterine and placental perfusion as well as fetal and placental growth. In the setting of NOS inhibition, ETA antagonism did not improve uterine or placental perfusion or fetal growth after 7 days of infusion irrespective of the degree of selectivity of the antagonist used. Conclusions ETA antagonism, irrespective of the degree of receptor selectivity, does not improve fetal growth or uteroplacental perfusion on day 7 of chronic NOS inhibition.

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Section: Discussionmentioning

confidence: 93%

Impact of Endothelin A Receptor Antagonist Selectivity in Chronic Nitric Oxide Synthase Inhibition-Induced Fetal Growth Restriction in the Rat

Neerhof

Synowiec

Khan

et al. 2010

Hypertension in Pregnancy

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“…However, most studies addressing ET-1 functional role in BP control originated from animal studies. ET-1 supports utero-placental vasculature contractile tone, which decreases near pregnancy term [ 398 ]. Activation of ETB receptor in rats is required for optimal pregnancy outcomes [ 399 ].…”

Section: Et-1 and Pregnancy Complicationsmentioning

confidence: 99%

Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine

et al. 2021

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Endothelin-1 (ET-1) is involved in the regulation of a myriad of processes highly relevant for physical and mental well-being; female and male health; in the modulation of senses, pain, stress reactions and drug sensitivity as well as healing processes, amongst others. Shifted ET-1 homeostasis may influence and predict the development and progression of suboptimal health conditions, metabolic impairments with cascading complications, ageing and related pathologies, cardiovascular diseases, neurodegenerative pathologies, aggressive malignancies, modulating, therefore, individual outcomes of both non-communicable and infectious diseases such as COVID-19. This article provides an in-depth analysis of the involvement of ET-1 and related regulatory pathways in physiological and pathophysiological processes and estimates its capacity as a predictor of ageing and related pathologies, a sensor of lifestyle quality and progression of suboptimal health conditions to diseases for their targeted prevention and as a potent target for cost-effective treatments tailored to the person.

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“…Activation of the ET/ET B pathway in healthy pregnancy is thought to be stimulated by the pregnancy hormone relaxin (10,42), and other factors including estrogen, vascular endothelial growth factor, and placental growth factor may play a role in this response as well (31,43,44). In addition, ET-1 contributes to the contractile tone of the uteroplacental vasculature, and this tone diminishes near term (2). These studies demonstrate that activation of the ET system is critical in maintaining a normal cardiovascular response to pregnancy.…”

Section: Et System In Normal Pregnancymentioning

confidence: 99%

Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females

Gillis

Sasser

Sullivan

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Endothelin-1 (ET-1) is a potent vasoconstrictor, and dysregulation of the endothelin (ET) system has been implicated in the development of hypertension. Sex differences in the ET system have been identified in ET receptor expression and activation, levels of ET-1, and downstream mediators of the ET system. More specifically, males have greater ET-1/ETA receptor activation, whereas females exhibit greater ETB receptor activation. These differences have been suggested to contribute to the sex differences observed in blood pressure control, with greater ETB receptor activation in females potentially acting as an important pathway contributing to the lower prevalence of hypertension in young females compared with age-matched males. This hypothesis is further supported by studies in pregnancy; the role of the ET system is enhanced during pregnancy, with dysregulation of the ET system resulting in preeclampsia. Further research is necessary to elucidate the relative roles of the ET system in blood pressure control in both sexes and to further explore the potential benefits of pharmacological ET blockade in women.

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The Role of Endogenous Endothelin in the Regulation of Uteroplacental and Renal Blood Flow During Pregnancy in Conscious Rats

Cited by 9 publications

References 23 publications

Impact of Endothelin A Receptor Antagonist Selectivity in Chronic Nitric Oxide Synthase Inhibition-Induced Fetal Growth Restriction in the Rat

Impact of Endothelin A Receptor Antagonist Selectivity in Chronic Nitric Oxide Synthase Inhibition-Induced Fetal Growth Restriction in the Rat

Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine

Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females

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