Endothelin-1 in Heart and Pulmonary Tissue in Experimental Heart Failure

Sirviö, Marja-Leena; Helin, Kristian; Stewen, Pia; Tikkanen, I.; Fyhrquist, Frej

doi:10.3109/08037059709062077

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Thus the pulmonary circulation appears to be the primary source of ET release in this porcine model of severe pacing-induced CHF. This is consistent with previous reports of increased levels of ET-1 in the lungs of CHF animals (15,46). Furthermore, Tsutamoto and co-workers (56) found a marked increase of pET levels from the pulmonary capillary wedge region compared with the pulmonary artery in patients with CHF, consistent with our findings.…”

Section: Discussionsupporting

confidence: 94%

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Kjekshus¹,

Smiseth²,

Klinge³

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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Endothelin (ET) contributes to the increased systemic vascular resistance and elevated cardiac filling pressures seen in congestive heart failure (CHF). We investigated to what extent ET-mediated vasoconstriction in CHF occurs through an endocrine action of elevated plasma ET or by an autocrine/paracrine mechanism related to induction of vascular ET gene expression. Three weeks of pacing (225 beats/min) induced a marked release of ET-1 from the pulmonary circulation with a sixfold elevation of arterial plasma ET in CHF pigs compared with sham-operated pigs. Arterial plasma ET was the strongest and only independent predictor of systemic vascular resistance. In contrast, vascular preproET-1 and ET-receptor mRNA expression were unaltered or decreased in CHF pigs and did not correlate with indexes of vascular tone. However, myocardial preproET-1 mRNA expression increased twofold in CHF pigs. PreproET-2 and preproET-3 mRNAs were not detectable in cardiovascular tissues. In conclusion, plasma ET was markedly increased because of an augmented release from the pulmonary circulation during CHF, and arterial plasma ET correlated with systemic vascular resistance. The absence of ET induction in the peripheral vasculature suggests that ET increases vascular tone during CHF by an endocrine, not an autocrine/paracrine, mechanism.

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Section: Discussionsupporting

confidence: 94%

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Kjekshus¹,

Smiseth²,

Klinge³

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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“…Therefore, we clari ed the relationship between endothelial dysfunction and HF by detecting ET-1 levels in myocardial tissue. Our study found that as compared to controls, the concentration of ET-1 was elevated in rats with acute HF and chronic HF induced by EAM, which is consistent with the reports from previous studies [23][24][25]. Therefore, endothelial dysfunction may play a crucial role in the development and progression of HF.…”

Section: Discusssionsupporting

confidence: 92%

Activation of ET/ETR axis in myocardial tissue characterizes heart failure induced by experimental autoimmune myocarditis

Yang

Tian

et al. 2023

Preprint

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Background: Endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilatory and vasoconstrictive effects and may play an important role in the development of heart failure. More and more studies have shown that endothelial-derived NO-mediated vasodilation is attenuated in heart failure patients. However, the role of ET-1 and its receptors in heart failure remains controversial. The aim of this study is to determine whether ET-1 and its receptor are activated in myocarditis and heart failure, and to explore the role of ET-1/ETR in heart failure. Methods: HE staining was used to detect myocardial inflammatory infiltration and myocarditis score, echocardiography to evaluate cardiac function, ELISA to detect serum ET-1 level, and immunohistochemistry and western blot to detect ETAR and ETBR expression in myocardial tissue of rats with myocarditis heart failure. Results: PCM-induced EAM rats tended to reach peak inflammation after 3 weeks of immunization and develop stable chronic HF at week 8 of immunization. Echocardiography was performed on day 21 and 56 of PCM-immunized rats, LVEDd and LVEDs were significantly increased in the EAM group compared to the control group at 3 weeks and 8 weeks while EF and FS were significantly reduced. Therefore, autoimmune myocarditis can induce both acute and chronic heart failure through a PCM-induced autoimmune myocarditis model. Moreover, HE staining revealed that inflammation persisted in EAM-induced acute and chronic heart failure. Serum ET-1 level detected by ELISA method was significantly increased. And immunohistochemistry and western blot indicated that ETAR, and ETBR protein expression in myocardial tissue were significantly elevated in acute heart failure and chronic heart failure. Conclusions: The ET-1/ETR axis were activated in both EAM-induced acute heart failure and chronic heart failure. The ET-1/ETR axis were positively correlated with heart failure and can be used as biomarkers to characterize heart failure.

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“…Conversely, mechanisms associated with a decrease in AFR in noncardiogenic pulmonary edema such as ARDS or high-altitude pulmonary edema cannot be explained by an increase in hydrostatic pressure causing an increase in NO release. In addition, patients with congestive heart failure have increased levels of ET-1 (48)(49)(50)(51) and ET-1 is released from endothelial cells when exposed to stretch or shear stress (11,52). Here, we provide evidence that ET-1, which is increased in cardiogenic and noncardiogenic pulmonary edema, increases endothelial NO levels, which are responsible for the decrease in AFR (see Figures 7 and 8).…”

Section: Discussionmentioning

confidence: 53%

Endothelin-1 Impairs Alveolar Epithelial Function via Endothelial ET_B Receptor

Comellas¹,

Briva²,

Dada³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Endothelin-1 (ET-1) is increased in patients with highaltitude pulmonary edema and acute respiratory distress syndrome, and these patients have decreased alveolar fluid reabsorption (AFR). Objectives: To determine whether ET-1 impairs AFR via activation of endothelial cells and nitric oxide (NO) generation. Methods: Isolated perfused rat lung, transgenic rats deficient in ET B receptors, coincubation of lung human microvascular endothelial cells (HMVEC-L) with rat alveolar epithelial type II cells or A549 cells, ouabain-sensitive 86 Rb 1 uptake. Measurements and Main Results: The ET-1-induced decrease in AFR was prevented by blocking the endothelin receptor ET B , but not ET A . Endothelial-epithelial cell interaction is required, as direct exposure of alveolar epithelial cells (AECs) to ET-1 did not affect Na,K-ATPase function or protein abundance at the plasma membrane, whereas coincubation of HMVEC-L and AECs with ET-1 decreased Na,K-ATPase activity and protein abundance at the plasma membrane. Exposing transgenic rats deficient in ET B receptors in the pulmonary vasculature (ET-B 2/2 ) to ET-1 did not decrease AFR or Na,K-ATPase protein abundance at the plasma membrane of AECs. Exposing HMVEC-L to ET-1 led to increased NO, and the ET-1-induced down-regulation of Na,K-ATPase was prevented by the NO synthase inhibitor L-NAME, but not by a guanylate cyclase inhibitor. Conclusions: We provide the first evidence that ET-1, via an endothelial-epithelial interaction, leads to decreased AFR by a mechanism involving activation of endothelial ET B receptors and NO generation leading to alveolar epithelial Na,K-ATPase down-regulation in a cGMP-independent manner.

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Endothelin-1 in Heart and Pulmonary Tissue in Experimental Heart Failure

Cited by 6 publications

References 26 publications

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Activation of ET/ETR axis in myocardial tissue characterizes heart failure induced by experimental autoimmune myocarditis

Endothelin-1 Impairs Alveolar Epithelial Function via Endothelial ET_B Receptor

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Endothelin-1 in Heart and Pulmonary Tissue in Experimental Heart Failure

Cited by 6 publications

References 26 publications

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF

Activation of ET/ETR axis in myocardial tissue characterizes heart failure induced by experimental autoimmune myocarditis

Endothelin-1 Impairs Alveolar Epithelial Function via Endothelial ETB Receptor

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Endothelin-1 Impairs Alveolar Epithelial Function via Endothelial ET_B Receptor