Contraction to endothelin-1 in pulmonary arteries from endotoxin-treated rats is modulated by endothelium

1995 ◽  
Vol 268 (6) ◽  
pp. H2260-H2266
Author(s):  
N. P. Curzen ◽  
M. J. Griffiths ◽  
T. W. Evans
Keyword(s):  
Pulmonary Artery ◽  
Receptor Antagonist ◽  
Contractile Response ◽  
Pulmonary Arteries ◽  
The Novel ◽  
Receptor Stimulation ◽  
Thromboxane A2 Receptor ◽  
Endothelin 1 ◽  
Etb Receptor ◽  
Potent Vasoconstrictor

Sepsis is characterized by hyporesponsiveness of vascular smooth muscle to pressor agents. Levels of the potent vasoconstrictor, endothelin-1 (ET-1), are elevated in animal models of sepsis and in patients. This study assesses the contractile response of pulmonary artery from endotoxin-pretreated rats to ET-1 to determine whether this contraction is modified by the endothelium. Both intact and denuded rings from endotoxin-pretreated rats exhibited hyporesponsiveness to ET-1, but the endothelium was found to be essential for maximal ET-1-induced contraction. Upon pretreatment of vessels with the cyclooxygenase inhibitor, indomethacin (10(-5) M), the novel ETB-receptor antagonist, BQ-788 (10(-8) and 10(-6) M), and the thromboxane A2-receptor antagonist, ICI-192605 (10(-5) M), each of these agents caused a reduction in the ET-1-induced contraction of endotoxin-pretreated rat pulmonary artery only in the presence of the endothelium but had no effect in endothelium-denuded vessels or in sham-treated groups. These findings demonstrate that ET-1-induced contraction in pulmonary arteries from septic rats is partially dependent upon an endothelially derived cyclooxygenase product, the release of which appears to involve ETB-receptor stimulation.

Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins

1994 ◽  
Vol 267 (1) ◽  
pp. H139-H147 ◽  
Author(s):  
T. M. Zellers ◽  
J. McCormick ◽  
Y. Wu
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Potent Vasoconstrictor ◽  
Eta Receptor Antagonist ◽  
Arteries And Veins

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascular bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric oxide (EDNO), and prostacyclin in isolated small porcine pulmonary arteries and veins under in vitro conditions. ET-1 caused concentration-dependent contractions in arteries and veins, augmented by the nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine, in pulmonary veins. BQ-123 (ETA-receptor antagonist) depressed the ET-1-induced contractions. Sarafotoxin S6C, an ETB-receptor agonist, caused contractions of pulmonary veins only. Endothelium-dependent relaxations to bradykinin and ET-1 were greater in pulmonary veins compared with arteries, inhibited by N omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxin S6C, ETB-receptor agonists, caused comparable endothelium-dependent relaxations in arteries and veins. ET-1 caused a fourfold greater increase in prostacyclin release in pulmonary veins compared with arteries. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmonary vessels and stimulates the release of EDNO and prostacyclin, which oppose the contractions to the peptide. The release of these endothelium-derived vasodilators appears greater in pulmonary veins.

Abstract P270: First Trimester Elevation in Circulating Endothelin-1 and Arterial Stiffness are Predictive of Late Pregnancy Preeclampsia

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Alexandria M Betz ◽  
Gary L Pierce ◽  
Donna A Santillan ◽  
Eric J Devor ◽  
Sabrina M Scroggins ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Late Pregnancy ◽  
Fold Increase ◽  
First Trimester ◽  
The Novel ◽  
Pregnancy Hypertension ◽  
Endothelin 1 ◽  
Potent Vasoconstrictor ◽  
Novel Concept ◽  
Nested Case Control

Preeclampsia (PE) is characterized by late pregnancy hypertension and proteinuria. PE causes significant morbidity for the maternal-fetal unit. Circulating endothelin-1 (ET-1), a potent vasoconstrictor, is elevated at the time of diagnosis of human PE. In addition, women with PE demonstrate arterial stiffness as early as the end of the first trimester. However, it is unknown if arterial stiffness is associated with a first trimester elevation in ET-1 and post-delivery placental ET-1. We hypothesized that 1) first trimester plasma ET-1 is elevated and is associated with arterial stiffness in women who develop PE; 2) first trimester ET-1 is predictive of PE; and 3) placental ET-1 is increased in PE. To address these questions, we performed a nested case-control study in women at risk for PE. First trimester plasma ET-1 was measured via ELISA; aortic stiffness and carotid beta-stiffness (CβS) were measured by carotid-femoral pulse-wave velocity (CFPWV) and carotid tonometry/ultrasound, respectively. While the maternal age of controls (n=126; age 30 ± 0.45 years) and PE (n=15; age 31 ± 1.3 years) were similar, the PE group had a higher first trimester BMI (35 ± 3 vs. 29 ± 1 kg/m 2 , p = 0.01), systolic (125 ± 2 vs. 113 ± 1 mmHg, p< 0.01) and diastolic blood pressure (68 ± 2 vs. 60 ± 1 mmHg, p< 0.01) compared with controls. In addition, first trimester plasma ET-1 (2.7 ± 0.4 vs. 2.0 ± 0.2 pg/mL, p < 0.01), CFPWV (7.2 ± 0.5 vs. 6.1 ± 0.2 m/s, p = 0.016), and CβS (8.4 ± 1.9 vs. 6.3 ± 0.3, p = 0.055) were higher in the PE group. Consistent with previous studies, third trimester plasma ET-1 was elevated in the PE group (2.9 ± 1.1 vs. 1.6 ± 0.1 pg/mL, p < 0.01) which paralleled a 2.5 fold increase in placental decidual ET-1 mRNA (p < 0.0001). ROC analyses showed that first trimester plasma ET-1 (AUC=0.71, p < 0.001) and CFPWV (AUC=0.70, p=0.014) were predictive of PE. This study supports the novel concept that elevated ET-1 in preeclampsia begins early in the first trimester and is associated with premature arterial stiffness. Further, these novel data suggest that ET-1 may play an important role in the first trimester prediction and pathogenesis of preeclampsia.

5-Hydroxytryptamine potentiates vasoconstrictor effect of endothelin-1

1992 ◽  
Vol 262 (4) ◽  
pp. H931-H936
Author(s):  
B. C. Yang ◽  
W. W. Nichols ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Receptor Antagonist ◽  
Channel Blocker ◽  
Contractile Response ◽  
Thromboxane A2 ◽  
Threshold Concentration ◽  
Endothelin 1 ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Ly 53857 ◽  
A2 Receptors

Interactions between 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) relative to contraction of rat aortic rings were examined in this study. Pretreatment of rings with threshold concentration of 5-HT potentiated the subsequent contractile response to ET-1. However, pretreatment with threshold concentration of ET-1 did not potentiate the contractile response to 5-HT. The 5-HT receptor antagonist LY 53857 blocked the synergistic contractile effects of 5-HT and ET-1 on rat aortic rings. Indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ 29548 also attenuated (P less than 0.05) the synergistic contractile effects of 5-HT and ET-1, suggesting release of thromboxane A2 or expression of thromboxane A2 receptors during this interaction. The calcium channel blocker verapamil also decreased the synergistic contractile effects of 5-HT and ET-1. Contraction of aortic rings by 5-HT alone was abolished by LY 53857 and attenuated by verapamil, diltiazem, and SQ 29548. Decrease in the force of contraction by verapamil as well as diltiazem indicates activation of voltage-dependent calcium channels during 5-HT-mediated contraction and perhaps during amplification of the vasoconstrictor activity of ET-1 by 5-HT.

Responses of isolated pulmonary arteries to synthetic peptide F-Met-Leu-Phe

1989 ◽  
Vol 257 (1) ◽  
pp. H107-H112
Author(s):  
R. E. Crowell ◽  
D. E. Van Epps ◽  
W. P. Reed
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Receptor Antagonist ◽  
Synthetic Peptide ◽  
Pulmonary Arteries ◽  
Histamine Receptor ◽  
Relaxation Response ◽  
Rabbit Pulmonary Artery ◽  
Resting Tension ◽  
Thromboxane Synthetase

The chemoattractant formyl-methionine-leucine-phenylalanine (FMLP) has recently been shown to possess spasmogenic properties in smooth muscle preparations from various organs. In this study we have investigated the actions of this peptide on isolated rabbit pulmonary artery (PA) ring segments. FMLP stimulated concentration-dependent constriction of PA at resting tension. However, in PA that had been preconstricted by norepinephrine, FMLP stimulated concentration-dependent relaxation. FMLP-stimulated PA constriction was inhibited by earlier exposure to indomethacin or to furegrelate, a thromboxane synthetase inhibitor, but not by earlier exposure to the H1 histamine receptor antagonist pyrilamine. FMLP-stimulated relaxation of PA was totally abolished by indomethacin but not by furegrelate or pyrilamine. Disruption of the endothelium in PA preparations decreased both the constriction and relaxation response to the peptide, suggesting that these cells were involved in these responses. These results indicate that the chemotactic factor FMLP can elicit constriction or relaxation of isolated PA, depending on the underlying active PA tension. In addition, both constriction and relaxation are dependent on cyclooxygenase products and intact endothelium.

Resolvin D1 reverses reactivity and Ca2+ sensitivity induced by ET-1, TNF-α, and IL-6 in the human pulmonary artery

2014 ◽  
Vol 307 (11) ◽  
pp. H1547-H1558 ◽  
Author(s):  
Roddy Hiram ◽  
Edmond Rizcallah ◽  
Chantal Sirois ◽  
Marco Sirois ◽  
Caroline Morin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Contractile Activity ◽  
Transmembrane Protein ◽  
Pulmonary Arteries ◽  
Resolvin D1 ◽  
Endothelin 1 ◽  
Inflammatory Status ◽  
Tnf Α

Pulmonary hypertension (PH) is a rare and progressive disease characterized by an inflammatory status and vessel wall remodeling, resulting in increased pulmonary artery resistance. During the last decade, treatments have been proposed; most of them target the endothelial pathways that stimulate smooth muscle cell relaxation. However, PH remains associated with significant morbidity. We hypothesized that inflammation plays a crucial role in the severity of the abnormal vasoconstriction in PH. The goal of this study was to assess the effects of resolvin D1 (RvD1), a potent anti-inflammatory agent, on the pharmacological reactivity of human pulmonary arteries (HPAs) via an in vitro model of induced hyperreactivity. The effects of RvD1 and monoacylglyceride compounds were measured on contractile activity and Ca2+ sensitivity developed by HPAs that had been pretreated (or not) under proinflammatory conditions with either 10 ng/ml TNF-α or 10 ng/ml IL-6 or under hyperreactive conditions with 5 nM endothelin-1. The results demonstrated that, compared with controls, 24-h pretreatment with TNF-α, IL-6, or endothelin-1 increased reactivity and Ca2+ sensitivity of HPAs as revealed by agonist challenges with 80 mM KCl, 1 μM serotonin (5-hydroxytryptamine), 30 nM U-46619, and 1 μM phorbol 12,13-dibutyrate. However, 300 nM RvD1 as well as 1 μM monoacylglyceride-docosapentaenoic acid monoglyceride strongly reversed the overresponsiveness induced by both proinflammatory and hyperreactive treatments. In pretreated pulmonary artery smooth muscle cells, Western blot analyses revealed that RvD1 treatment decreased the phosphorylation level of CPI-17 and expression of transmembrane protein member 16A while increasing the detection of G protein-coupled receptor 32. The present data demonstrate that RvD1, a trihydroxylated docosahexaenoic acid derivative, decreases induced overreactivity in HPAs via a reduction in CPI-17 phosphorylation and transmembrane protein member 16A expression.

scholarly journals Block of Endothelin-1-induced release of thromboxane A2 from the guinea pig lung and nitric oxide from the rabbit kidney by a selective ETB receptor antagonist, BQ-788

1994 ◽  
Vol 113 (4) ◽  
pp. 1257-1262 ◽  
Author(s):  
Pedro D'Orléans-Juste ◽  
Audrey Claing ◽  
Sabine Télémaque ◽  
Marie-Claude Maurice ◽  
Mitsuo Yano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Thromboxane A2 ◽  
Rabbit Kidney ◽  
Endothelin 1 ◽  
Etb Receptor

Analysis of vasocontractile responses to endothelin-1 in rabbit retinal vessels using an ETA receptor antagonist and an ETB receptor agonist

Life Sciences ◽  
1993 ◽  
Vol 53 (6) ◽  
pp. PL111-PL115 ◽  
Author(s):  
Kazuo Takei ◽  
Tsuyoshi Sato ◽  
Tomohito Nonoyama ◽  
Takashi Miyauchi ◽  
Katsutoshi Goto
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Retinal Vessels ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Eta Receptor Antagonist

Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats

2006 ◽  
Vol 290 (2) ◽  
pp. L284-L290 ◽  
Author(s):  
Letitia Weigand ◽  
J. T. Sylvester ◽  
Larissa A. Shimoda
Keyword(s):  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Pulmonary Arteries ◽  
Rho Kinase ◽  
Inhibitory Effect ◽  
Endothelin 1 ◽  
Intracellular Ca ◽  
Gf 109203X ◽  
Tk Inhibitors ◽  
Potent Vasoconstrictor

Endothelin-1 (ET-1), a potent vasoconstrictor, is believed to contribute to the pathogenesis of hypoxic pulmonary hypertension. Previously we demonstrated that contraction induced by ET-1 in intrapulmonary arteries (IPA) from chronically hypoxic (CH) rats occurred independently of changes in intracellular Ca2+ concentration ([Ca2+]i), suggesting that ET-1 increased Ca2+ sensitivity. The mechanisms underlying this effect are unclear but could involve the activation of myosin light chain kinase, Rho kinase, PKC, or tyrosine kinases (TKs), including those from the Src family. In this study, we examined the effect of pharmacological inhibitors of these kinases on maximum tension generated by IPA from CH rats (10% O2 for 21 days) in response to ET-1. Experiments were conducted in the presence of nifedipine, an L-type Ca2+ channel blocker, to isolate the component of contraction that occurred without a change in [Ca2+]i. The mean change in tension caused by ET-1 (10−8 M) expressed as a percent of the maximum response to KCl was 184.0 ± 39.0%. This response was markedly inhibited by the Rho kinase inhibitors Y-27632 and HA-1077 and the TK inhibitors genistein, tyrphostin A23, and PP2. In contrast, staurosporine and GF-109203X, inhibitors of PKC, had no significant inhibitory effect on the tension generated in response to ET-1. We conclude that the component of ET-1-induced contraction that occurs without a change in [Ca2+]i in IPA from CH rats requires activation of Rho kinase and TKs, but not PKC.

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