Leukotriene receptors on human pulmonary vascular endothelium

Ortiz, J.L.; Gorenne, Isabelle; Cortijo, Julio; Seller, A.; Labat, Carlos; Sarriá, Benjamı́n; Abram, Trevor S.; Gardiner, P.J.; Morcillo, E; Brink, Charles

doi:10.1111/j.1476-5381.1995.tb16627.x

Cited by 55 publications

(35 citation statements)

References 23 publications

(44 reference statements)

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“…MacLean et al (1993) reported that treatment with L-NAME enhances responses to sumatriptan in human isolated pulmonary artery. Loss of endothelial integrity in human pulmonary artery preparations subjected to cold storage overnight (Ortiz et al, 1995) may explain the ®nding of greater E max values for sumatriptan by MacLean et al (1996) compared to other studies including this one (see above).…”

Section: Role Of the Endothelium In The Responses To 5-ht And Sumatrimentioning

confidence: 82%

“…at 48C for transport to the laboratory where pulmonary arteries and veins were dissected free from parenchymal tissue and the preparations were cut in rings (3 ± 4 mm length62 ± 5 mm internal diameter). Tissues were used within 3 h of surgery as we have previously shown that preparations stored overnight often failed to show an endothelium-dependent relaxation when stimulated with histamine (Ortiz et al, 1995). In some preparations the endothelium was removed by inserting into the lumen of each ring a roughened wooden stick and rubbing gently the intimal surface of the blood vessel.…”

Section: Preparation Of Human Pulmonary Blood Vesselsmentioning

confidence: 99%

“…These experiments were carried out as previously described (Ortiz et al, 1995). In brief, the preparations were allowed to equilibrate for 69 ± 90 min (with changes in bath¯uid every 20 min) before any pharmacological intervention occurred.…”

Section: Functional Studiesmentioning

confidence: 99%

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Characterization of 5‐HT receptors on human pulmonary artery and vein: functional and binding studies

Cortijo

Martı́-Cabrera

Bernabeu

et al. 1997

British J Pharmacology

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1 This study aimed to investigate the 5-hydroxytryptamine (5-HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the responses to 5-HT, sumatriptan, ergotamine, serotonin-O-carboxymethyl-glycyl-tyrosinamide (SCMGT), a-methyl 5-HT (a-Me) and 2-methyl 5-HT (2-Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists. 2 All agonists produced concentration-dependent contractions of human pulmonary artery and vein preparations. The order of potency (7log EC 50 values) was ergotamine (6.88)45-HT (6.41)5SCMGT (6.20)=sumatriptan (6.19) 5a-Me (6.04) in the artery, and ergotamine (7.84)45-HT (6.96)4suma-triptan (6.60)=a-Me (6.56)4SCMGT (6.09) in the vein. The potency of each agonist, except for SCMGT, was greater in vein than in artery preparations. Contractile responses to 5-HT were similar in intact and endothelium-denuded preparations but responses to sumatriptan were enhanced in artery rings without endothelium. 3 GR127935 (1 nM to 0.5 mM) produced an unsurmountable antagonism of the response to 5-HT, sumatriptan, ergotamine and SCMGT. Ritanserin (1 nM to 1 mM) also reduced the maximum contractile responses to 5-HT, ergotamine and a-Me in artery and vein preparations without aecting those to sumatriptan and SCMGT. In endothelium-denuded preparations, surmountable antagonism of sumatriptan by GR127935 (in the presence of ritanserin) and of a-Me by ritanserin (in the presence of GR127935) allowed for the calculation of the apparent pK B values of GR127935 (9.17+0.11 in artery and 9.11+0.05 in vein) and ritanserin (8.82+0.09 in artery and 8.98+0.12 in vein). 4 WAY100635 (1 nM to 1 mM), zacopride (1 nM to 1 mM), or SB204070 (1 nM) did not signi®cantly alter the concentration-response curves for 5-HT, sumatriptan, ergotamine, SCMGT or 2-Me in human pulmonary artery or vein thus indicating that 5-HT 1A , 5-HT 3 and 5-HT 4 receptors are presumably not involved in the contractile response to these agonists. 5 Binding studies using selective radioligands for dierent 5-HT receptors could not detect the presence of 5-HT 1A receptor binding in human pulmonary blood vessels whereas the 5-HT 1B/1D radioligand [ 3 H]-5-CT signi®cantly labelled a population of speci®c binding sites in both vessel types. The presence of 5-HT 2A receptors could also be inferred from the level of binding of [ 3 H]-ketanserin to membranes obtained from human pulmonary vessels, although signi®cance could not be reached for arteries. 5-HT 4 speci®c receptor binding was scarce in veins and absent in the case of arteries. 6 These ®ndings indicate that the human pulmonary artery and vein have a mixed functional population of 5-HT 1B/1D and 5-HT 2A receptors mediating the contractile response to 5-HT which is consistent with results of the binding studies.

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Section: Role Of the Endothelium In The Responses To 5-ht And Sumatrimentioning

confidence: 82%

Section: Preparation Of Human Pulmonary Blood Vesselsmentioning

confidence: 99%

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Characterization of 5‐HT receptors on human pulmonary artery and vein: functional and binding studies

Cortijo

Martı́-Cabrera

Bernabeu

et al. 1997

British J Pharmacology

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“…However, while a proinflammatory environment down-regulates CysLT 2 receptor expression in human umbilical vein endothelial cells (HUVECs) [42], CysLT 1 receptor expression is induced in HUVECs under such conditions [43]. Furthermore, studies of isolated arteries have demonstrated endothelium-dependent contractions through CysLT 1 receptor signaling [44,45]. Taken together, those observations suggest that a balance of CysLT receptor subtype expression may determine the LT-induced endothelium-dependent vasomotor responses.…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Leukotriene Signaling in Atherosclerosis and Ischemia

Bäck

2008

Cardiovasc Drugs Ther

120

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“…Although the lung resection and pulmonary artery dissection were performed at the most distant point from and completely free of tumour tissue, we cannot rule out a possible influence of the inflammatory neoplastic microenvironment, which may be one limitation of this study. was removed from some pulmonary artery rings, as described previously [14]. Arteries were used within 1 to 5 h post-surgery.…”

Section: Preparation Of Pulmonary Artery Ringsmentioning

confidence: 99%

Direct effect of cigarette smoke on human pulmonary artery tension

Ortiz¹,

Milara²,

Juan³

et al. 2010

Pulmonary Pharmacology & Therapeutics

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESS M A N U S C R I P T A C C E P T E D ARTICLE IN PRESS2 AbstractThe effect of chronic cigarette smoke on pulmonary artery (PA) tension has been studied extensively; nevertheless, the direct effect of cigarette smoke is poorly understood. We investigated the direct effect of cigarette smoke extract (CSE) on PA tension in non-smokers, smokers, and COPD patients in vitro. PA samples from 35 patients who underwent lung resection were examined by measuring isometric tension in response to increasing serotonin concentrations. CSE dose-dependently inhibited the response to serotonin in smokers and COPD patients, and to a lesser extent in nonsmokers. CSE-induced relaxation was similarly inhibited by the nonspecific nitric oxide synthase (NOS) inhibitor L-NOARG and the specific inducible NOS (iNOS) inhibitor L-NIL, mainly in non-smokers and smokers, and to a lesser extent in COPD patients.Immunostaining of iNOS in PA samples was greater for smokers and COPD patients compared with non-smokers, which explains the lesser effect of CSE on PA tension in non-smokers. Moreover, CSE induced the release of nitrite via iNOS in human PA smooth muscle cells. In conclusion, CSE inhibition of serotonin-induced PA contraction was mediated mainly by iNOS in non-smokers, smokers, and COPD patients, but in different ways, which may be explained by differential iNOS expression in the PA of these patients.

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Leukotriene receptors on human pulmonary vascular endothelium

Cited by 55 publications

References 23 publications

Characterization of 5‐HT receptors on human pulmonary artery and vein: functional and binding studies

Characterization of 5‐HT receptors on human pulmonary artery and vein: functional and binding studies

Leukotriene Signaling in Atherosclerosis and Ischemia

Direct effect of cigarette smoke on human pulmonary artery tension

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