Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

Hedegaard, Elise Røge; Stankevičius, Edgaras; Simonsen, Ulf; Fröbert, Ole

doi:10.1186/1472-6793-11-8

Cited by 15 publications

(18 citation statements)

References 59 publications

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“…For example, hyperoxia induced vasoconstriction in coronary arteries of pigs [34, 63] and in carotid vessels from dogs [64], but induced vasodilation in renal vessels of the dog [65], whereas no response to hyperoxia was observed in the arterioles of the mesentery of the rat and cat [19, 66]. …”

Section: Discussionmentioning

confidence: 99%

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Attaye

Smulders

Waard

et al. 2017

ICMx

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BackgroundHyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Increasing evidence suggests that hyperoxia induces vasoconstriction in the systemic (micro)circulation, potentially affecting organ perfusion. This study addresses effects of hyperoxia on viability, proliferative capacity, and on pathways affecting vascular tone in cultured human microvascular endothelial cells (hMVEC).MethodshMVEC of the systemic circulation were exposed to graded oxygen fractions of 20, 30, 50, and 95% O2 for 8, 24, and 72 h. These fractions correspond to 152, 228, 380, and 722 mmHg, respectively. Cell proliferation and viability was measured via a proliferation assay, peroxynitrite formation via anti-nitrotyrosine levels, endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) levels via q-PCR and western blot analysis.ResultsExposing hMVEC to 50 and 95% O2 for more than 24 h impaired cell viability and proliferation. Hyperoxia did not significantly affect nitrotyrosine levels, nor eNOS mRNA and protein levels, regardless of the exposure time or oxygen concentration used. Phosphorylation of eNOS at the serine 1177 (S1177) residue and ET-1 mRNA levels were also not significantly affected.ConclusionsExposure of isolated human microvascular endothelial cells to marked hyperoxia for more than 24 h decreases cell viability and proliferation. Our results do not support a role of eNOS mRNA and protein or ET-1 mRNA in the potential vasoconstrictive effects of hyperoxia on isolated hMVEC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0135-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Attaye

Smulders

Waard

et al. 2017

ICMx

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“…Appropriate oxygen concentration was obtained by gassing the organ bath through pimpstones allowing rapid equilibration of the oxygen tension with air or 5% CO 2 in N 2 , which resulted in 1% O 2 in the organ bath (Hedegaard et al, 2011). The arteries were incubated with vehicle or XE991; after 30 minutes, they were contracted with vasopressin (10-100 nM) to obtain similar contraction levels.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury

Hedegaard

Johnsen

Povlsen

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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The voltage-gated K V 7 (KCNQ) potassium channels are activated by ischemia and involved in hypoxic vasodilatation. We investigated the effect of K V 7 channel modulation on cardiac ischemia and reperfusion injury and its interaction with cardioprotection by ischemic preconditioning (IPC). Reverse-transcription polymerase chain reaction revealed expression of K V 7.1, K V 7.4, and K V 7.5 in the left anterior descending rat coronary artery and all K V 7 subtypes (K V 7.1-K V 7.5) in the left and right ventricles of the heart. Isolated hearts were subjected to no-flow global ischemia and reperfusion with and without IPC. Infarct size was quantified by 2,3,5-triphenyltetrazolium chloride staining. Two blockers of K V 7 channels, XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone] (10 mM) and linopirdine (10 mM), reduced infarct size and exerted additive infarct reduction to IPC. An opener of K V 7 channels, flupirtine (10 mM) abolished infarct size reduction by IPC. Hemodynamics were measured using a catheter inserted in the left ventricle and postischemic left ventricular recovery improved in accordance with reduction of infarct size and deteriorated with increased infarct size. XE991 (10 mM) reduced coronary flow in the reperfusion phase and inhibited vasodilatation in isolated small branches of the left anterior descending coronary artery during both simulated ischemia and reoxygenation. K V 7 channels are expressed in rat coronary arteries and myocardium. Inhibition of K V 7 channels exerts cardioprotection and opening of K V 7 channels abrogates cardioprotection by IPC. Although safety issues should be further addressed, our findings suggest a potential role for K V 7 blockers in the treatment of ischemiareperfusion injury.

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“…Superoxide and NO rapidly react with each other, thereby resulting in the loss of each other's bioactivity [12]. In this regard, exposure of isolated endothelium-intact coronary arteries to hypoxia has been suggested to stimulate endogenous NO production by endothelial cells in several animal species including the rat [13], rabbit [14], dog [15], pig [16], and humans [17]. Therefore, it is no wonder that if coronary artery endothelium is present and functional, the increased superoxide in the smooth muscle in response to hypoxia is trapped and neutralized by endogenous NO released from the endothelium.…”

Section: Discussionmentioning

confidence: 99%

Responsiveness of Coronary Arteries to Nitroglycerin under Hypoxia: The Importance of the Endothelium

Tawa

Shimosato²,

Saito³

et al. 2017

Pharmacology

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Background/Aims: Nitroglycerin is widely used as a coronary vasodilator in the treatment of ischemic heart diseases. This study investigated the influence of hypoxia on nitroglycerin-induced relaxation in endothelium-intact and -denuded rabbit, monkey, and porcine coronary arteries. Methods: Helically cut strips of coronary arteries were suspended in organ chambers, and isometric tension was recorded. Results: Nitroglycerin concentration dependently relaxed endothelium-intact rabbit coronary arteries, which were not different under normoxic and hypoxic conditions. On the other hand, nitroglycerin-induced relaxation of endothelium-denuded arteries was significantly attenuated by hypoxia. Similarly, the relaxant response of endothelium-intact monkey coronary arteries to nitroglycerin was not affected by hypoxia, whereas that of endothelium-denuded arteries was impaired. As is the case with rabbit and monkey coronary arteries, exposure to hypoxia resulted in impaired relaxation by nitroglycerin in endothelium-denuded but not endothelium-intact porcine coronary arteries. Conclusion: These findings suggest that coronary endothelium plays a pivotal role in preventing the hypoxia-induced impairment of nitroglycerin responsiveness, regardless of the animal species.

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Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

Cited by 15 publications

References 59 publications

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury

Responsiveness of Coronary Arteries to Nitroglycerin under Hypoxia: The Importance of the Endothelium

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