Endothelin receptor-mediated vasodilatation: Effects of organ culture

Nilsson, David; Wackenfors, Angelica; Gustafsson, Lotta; Paulsson, Per; Ingemansson, Richard; Edvinsson, Lars; Malmsjö, Malin

doi:10.1016/j.ejphar.2007.09.031

Cited by 17 publications

(9 citation statements)

References 38 publications

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“…This finding is partly in contrast to previous reports on human, rodent and porcine nonpulmonary systemic vessels which have indicated that organ culture may induce an upregulation of contractile ET B receptors located on vascular smooth muscle cells [40,41] or a downregulation of dilatory endothelial ET B receptors [42]. In the present study, incubation did not induce any statistically significant changes in response to ET receptor stimulation even though there was a trend towards increased S6c sensitivity in the pulmonary arteries after incubation.…”

Section: Discussioncontrasting

confidence: 55%

Endotoxin Induces Differentiated Contractile Responses in Porcine Pulmonary Arteries and Veins

et al. 2010

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Background/Aims: Sepsis-induced lung injury is characterized by pulmonary hypertension, edema and deteriorated gas exchange. As in vivo studies have indicated that bacterial endotoxin predominantly induces a pulmonary venous constriction, we aimed to investigate effects of endotoxin on isolated porcine pulmonary vessels. Methods: Pulmonary arteries and veins were examined using in vitro isometric force recordings. Endothelin-receptor protein expression and distribution were analyzed by Western blot and immunohistochemistry. Freshly isolated preparations and vessels incubated (24 h) with/without endotoxin (10 µg·ml^–1) were compared. The contractile responses to phenylephrine, UK14.304, U46619, PGF₂_α, endothelin-1 (ET-1) and sarafotoxin were recorded, as well as the relaxation in response to acetylcholine, isoproterenol and nitroprusside. Results: In freshly isolated vessels, phenylephrine-induced contractions had a 5-times larger amplitude in arteries than in veins. The amplitude of the contractions in response to sarafotoxin was nearly 2 times larger in veins than in arteries, but there was no difference in responses to ET-1. Endotoxin markedly reduced phenylephrine-induced contractions in both arteries and veins, whereas the responses to ET-1 and sarafotoxin were augmented in veins only. No apparent changes in ET receptor expression or distribution were detected with Western blot or immunohistochemistry. Conclusion: Endotoxin differentially and selectively alters the contractile responses of porcine pulmonary vessels in vitro, towards a situation where the α-1 adrenergic responses of arteries are attenuated and the ET responses of veins are augmented. In situations with high adrenergic activity and high circulating ET levels, such as sepsis, these results may provide a mechanism contributing to pulmonary hypertension and edema formation.

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Section: Discussioncontrasting

confidence: 55%

Endotoxin Induces Differentiated Contractile Responses in Porcine Pulmonary Arteries and Veins

et al. 2010

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“…In vivo studies have shown that ERK1/2 inhibition attenuates cerebral blood flow reduction and vasoconstriction after subarachnoid hemorrhage in rats and also prevents the upregulation of vascular endothelin ET B receptors (Beg et al 2006). In addition, ERK1/2 are involved in the upregulation of endothelin ET A and ET B receptors in porcine coronary arteries (Nilsson et al 2008) and ET B receptors in rat cerebral arteries (Henriksson et al 2004). Furthermore, Sommer and collaborators (2002) have demonstrated that patients with erectile dysfunction exhibited more active ERK1/2 in the cavernosal smooth muscle than did patients with normal erectile function.…”

Section: Discussionmentioning

confidence: 99%

DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Carneiro

Giachini

Lima

et al. 2008

Can. J. Physiol. Pharmacol.

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The penis is kept in the flaccid state mainly via a tonic activity of norepinephrine and endothelins (ETs). ET-1 is important in salt-sensitive forms of hypertension. We hypothesized that cavernosal responses to ET-1 are enhanced in deoxycorticosterone acetate (DOCA)-salt mice and that blockade 1 This article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.2Corresponding author (e-mail: E-mail: fcarneiro@mcg.edu). NIH Public Access

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“…Pathological conditions such as hypertension, atherosclerosis and diabetes are often associated with proliferation and differentiation of vascular smooth muscle cells and subsequent structural changes in the vascular wall [10]. Organ culture of rat coronary arteries induces upregulation of expression of contractile endothelin type-B receptors on VSMCs, thereby mimicking atherosclerosis and CAD [11], [12]. Organ culture also induces downregulation of the contractility of angiotensin-II receptors, thereby reflecting the phenotypic changes in human coronary arteries from patients with ischemic heart disease [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of 5-Hydroxytryptamine Receptor Signaling in Coronary Arteries after Organ Culture

et al. 2014

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Background5-Hydroxytryptamine (5-HT) is a powerful constrictor of coronary arteries and is considered to be involved in the pathophysiological mechanisms of coronary-artery spasm. However, the mechanism of enhancement of coronary-artery constriction to 5-HT during the development of coronary artery disease remains to be elucidated. Organ culture of intact blood-vessel segments has been suggested as a model for the phenotypic changes of smooth muscle cells in cardiovascular disease.Methodology/Principal FindingsWe wished to characterize 5-HT receptor-induced vasoconstriction and quantify expression of 5-HT receptor signaling in cultured rat coronary arteries. Cumulative application of 5-HT produced a concentration-dependent vasoconstriction in fresh and 24 h-cultured rat coronary arteries without endothelia. 5-HT induced greater constriction in cultured coronary arteries than in fresh coronary arteries. U46619- and CaCl2-induced constriction in the two groups was comparable. 5-HT stimulates the 5-HT2A receptor and cascade of phospholipase C to induce coronary vasoconstriction. Calcium influx through L-type calcium channels and non-L-type calcium channels contributed to the coronary-artery constrictions induced by 5-HT. The contractions mediated by non-L-type calcium channels were significantly enhanced in cultured coronary arteries compared with fresh coronary arteries. The vasoconstriction induced by thapsigargin was also augmented in cultured coronary arteries. The decrease in Orai1 expression significantly inhibited 5-HT-evoked entry of Ca2+ in coronary artery cells. Expression of the 5-HT2A receptor, Orai1 and STIM1 were augmented in cultured coronary arteries compared with fresh coronary arteries.ConclusionsAn increased contraction in response to 5-HT was mediated by the upregulation of 5-HT2A receptors and downstream signaling in cultured coronary arteries.

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Endothelin receptor-mediated vasodilatation: Effects of organ culture

Cited by 17 publications

References 38 publications

Endotoxin Induces Differentiated Contractile Responses in Porcine Pulmonary Arteries and Veins

Endotoxin Induces Differentiated Contractile Responses in Porcine Pulmonary Arteries and Veins

DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Upregulation of 5-Hydroxytryptamine Receptor Signaling in Coronary Arteries after Organ Culture

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