Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats

Wang, Jinwei; Li, Aiying; Guo, Qiuhong; Guo, Yajing; Weiss, J. Woodrow; Ji, En-Sheng

doi:10.14814/phy2.13050

Cited by 10 publications

(4 citation statements)

References 43 publications

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“…At 4 months of age, ET-1 tissue levels were increased in coronary arteries from prenatal hypoxia females only, while ET-1-mediated vasoconstriction and plasma levels of ET-1 were not affected by prenatal hypoxia in either sex. Previous research in an adult rat model of chronic intermittent hypoxia reported an enhanced ET-1 expression in coronary vessels that was accompanied with an enhanced ET-1-mediated response [ 63 ]. Thus, it can be suggested that prenatal hypoxia may have an adaptive response in that, although there was an increase in ET-1 expression, this was not accompanied by an increased ET-1-mediated coronary artery responsiveness.…”

Section: Discussionmentioning

confidence: 99%

The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring

et al. 2022

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Prenatal hypoxia predisposes the offspring to the development of cardiovascular (CV) dysfunction in adult life. Using a rat model, we assessed the effect of prenatal hypoxia on vasoconstrictive and vasodilative mechanisms in left anterior descending coronary arteries of 4- and 9.5-month-old offspring. Endothelium-dependent relaxation to methylcholine and vasoconstriction responses to endothelin-1 (ET-1) were assessed by wire myography. Prenatal hypoxia impaired endothelium-dependent vasodilation in 4- and 9.5-month-old offspring. Inhibition of nitric oxide (NO) synthase prevented coronary artery relaxation in all groups. Inhibition of prostaglandin H synthase (PGHS) improved relaxation in prenatally hypoxic males and tended to improve vasorelaxation in females, suggesting that impaired vasodilation was mediated via increased PGHS-dependent vasoconstriction. An enhanced contribution of endothelium-dependent hyperpolarization to coronary artery vasodilation was observed in prenatally hypoxic males and females. No changes in endothelial NO synthase (eNOS) and PGHS-1 expressions were observed, while PGHS-2 expression was decreased in only prenatally hypoxic males. At 4 months, ET-1 responses were similar between groups, while ETB inhibition (with BQ788) tended to decrease ET-1-mediated responses in only prenatally hypoxic females. At 9.5 months, ET-1-mediated responses were decreased in only prenatally hypoxic females. Our data suggest that prenatal hypoxia has long-term similar effects on the mechanisms of impaired endothelium-dependent vasodilation in coronary arteries from adult male and female offspring; however, coronary artery contractile capacity is impaired only in prenatally hypoxic females. Understanding the mechanistic pathways involved in the programming of CV disease may allow for the development of therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring

et al. 2022

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“…Both hypoxia-inducible factors (HIF) 1 and 2 and NF-B respond to IH by modulating the oxidative stress and inflammatory pathways and cell apoptosis in endothelial cells (26,53). Moreover, IH elicits changes in the gene expression and secretion of proinflammatory cytokines (51) and adipokines (27), affects nitric oxide coupling (6), and endothelin-1 and endothelin receptors (69), and increases the circulating levels of vascular endothelial growth factor (2), which has been shown to be implicated in endothelial wound healing with serum of OSA patients (10). In this context of IH, it could be possible that the response of each cell to a time-varying environment could involve slowand fast-response mechanisms, which would be mainly driven by the average hypoxia throughout the cycle and by the rate and magnitude of hypoxic cycling, respectively.…”

Section: Discussionmentioning

confidence: 99%

Frequency and magnitude of intermittent hypoxia modulate endothelial wound healing in a cell culture model of sleep apnea

Campillo

Falcones

Montserrat

et al. 2017

Journal of Applied Physiology

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Intermittent hypoxia (IH) has been implicated in the cardiovascular consequences of obstructive sleep apnea (OSA). However, the lack of suitable experimental systems has precluded assessment as to whether IH is detrimental, protective, or both for the endothelium. The aim of the work was to determine the effects of frequency and amplitude of IH oxygenation swings on aortic endothelial wound healing. Monolayers of human primary endothelial cells were wounded and subjected to constant oxygenation (1%, 4%, 13%, or 20% O) or IH at different frequencies (0.6, 6, or 60 cycles/h) and magnitude ranges (13-4% O or 20-1% O), using a novel well-controlled system, with wound healing being measured after 24 h. Cell monolayer repair was similar at 20% O and 13% O, but was considerably increased (approximately twofold) in constant hypoxia at 4% O The magnitude and frequency of IH considerably modulated wound healing. Cycles ranging 13-4% O at the lowest frequency (0.6 cycles/h) accelerated endothelial wound healing by 102%. However, for IH exposures consisting of 20% to 1% O oscillations, wound closure was reduced compared with oscillation in the 13-4% range (by 74% and 44% at 6 cycles/h and 0.6 cycles/h, respectively). High-frequency IH patterns simulating severe OSA (60 cycles/h) did not significantly modify endothelial wound closure, regardless of the oxygenation cycle amplitude. In conclusion, the frequency and magnitude of hypoxia cycling in IH markedly alter wound healing responses and emerge as key factors determining how cells will respond in OSA. Intermittent hypoxia (IH) induces cardiovascular consequences in obstructive sleep apnea (OSA) patients. However, the vast array of frequencies and severities of IH previously employed in OSA-related experimental studies has led to controversial results on the effects of IH. By employing an optimized IH experimental system here, we provide evidence that the frequency and magnitude of IH markedly alter human aortic endothelial wound healing, emerging as key factors determining how cells respond in OSA.

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“…ET produced by endothelial cells and other cell types is one of the most investigated molecules among vascular biology, which functions as an effective endothelium‐derived vasoconstrictor and may participate in mechanisms leading to hypertension . ET‐1 is one of the three isoforms of ET that functions as a powerful vasoconstrictor produced by the vascular endothelium cells and plays a significant role in the cardiovascular changes . Endothelins bind to ETRs to initiate their downstream effects.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of PPAR‐γ against pregnancy‐induced hypertension by differential ETR expression in rat models

Ruan

Shen

et al. 2017

J of Cellular Biochemistry

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This study aims to investigate the effects of PPAR-γ on rats with pregnancy-induced hypertension (PIH) by regulating endothelin receptor (ETR). A total of 60 pregnant Wistar rats were selected, and 50 rats were used to establish endotoxin induced PIH rat models. Rats were equally assigned into PIH-NS, PIH-5 mg/kg RM, PIH-10 mg/kg RM, PIH-100 mg/kg ETR, and PIH-200 mg/kg ETR groups, and the rest 10 rats were assigned to a the control group. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used for determining mRNA and protein expressions of PPAR-γ and ET R, respectively. Protein expression of ET-1 was detected by immunohistochemistry. Results show that On the 22nd day of pregnancy, compared with the PIH-NS group, SBP decreased in other groups, and platelet concentration increased most significantly in the PIH-10 mg/kg RM and PIH-200 mg/kg ETR groups. Compared with the control, PIH-10 mg/kg RM and PIH-200 mg/kg ETR groups, the increase in the expression of ET-1 and ET R was most significant in the PIH-NS group. Compared with the control and PIH-10 mg/kg RM groups, expression of PPAR-γ was lower in the PIH-NS, PIH-5 mg/kg RM, PIH-100 mg/kg ETR, and PIH-200 mg/kg ETR groups. Compared with the PIH-NS, PIH-100 mg/kg ETR and PIH-200 mg/kg ETR groups, PPAR-γ expression was significantly higher in the PIH-5 mg/kg RM group (all P < 0.05). Based on our findings, we conclude that PPAR-γ activation inhibits ETR expression and reduces the effect of ET-1 on vascular contraction thereby delaying PIH progression.

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Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats

Cited by 10 publications

References 43 publications

The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring

The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring

Frequency and magnitude of intermittent hypoxia modulate endothelial wound healing in a cell culture model of sleep apnea

Protective effects of PPAR‐γ against pregnancy‐induced hypertension by differential ETR expression in rat models

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