PubMed Health⌕ Search

Biomedical subjects

F Stanke-Labesque

Publications and source records attributed to F Stanke-Labesque.

29 records · Page 2Linked to original sources
PubMed2000

Vasoconstrictor effects of iso-prostaglandin F2alpha type-III (8-iso-prostaglandin F2alpha) on human saphenous veins.

Free radical generation can initiate the peroxidation of arachidonic acid, resulting in a non-cyclooxygenase-dependent production of bioactive prostaglandin F2-like compounds. We have investigated the effects of iso-prostaglandin F2alpha type III, (iPF2alpha-III, formerly named 8-iso prostaglandin F2alpha) on human saphenous veins, and characterized the underlying mechanisms. In organ baths, the contractile effects of iPF2alpha-III were tested on saphenous vein rings coming from 22 patients. iPF2alpha-III induced concentration-dependent contractions of isolated human saphenous veins. The maximal contraction did not differ significantly from that of prostaglandin F2alpha (PGF2alpha). The pD2 values for iPF2alpha-III, PGF2alpha, endothelin-1 (ET-1), and U46619 (a stable thromboxane A2 mimetic) were 6.31+/-0.12, 5.66+/-0.13, 7.37+/-0.08, and 7.99+/-0.31, respectively (p < 0.001 for U46619 vs. iPF2alpha-III and PGF2alpha; and ET-1 vs. PGF2alpha). Emax values of iPF2alpha-III, PGF2alpha, ET-1, and U46619 were 137.7+/-24.3%, 145.9+/-7.5%, 92.9+/-16.8%, and 238.7+/-23.7%, respectively (p < 0.001 for U46619 vs. iPF2alpha-III, PGF2alpha and ET-1; and for PGF2alpha vs. ET-1). The responses to iPF2alpha-III were inhibited by GR 32191 10(-7) M, a TP-receptor antagonist, without affecting the maximal response (pD2 values were 5.98+/-0.06 in the absence, and 5.22+/-0.05 in the presence of GR32191; p < 0.001). Concentration-effect curves to iPF2alpha-III were not affected by phosphoramidon 10(-5) M (an endothelin converting enzyme inhibitor), BQ123 10(-6) M (a selective ET(A)-receptor antagonist), BQ788 10(-6) M (a selective ET(B)-receptor antagonist), and indomethacin 10(-5) M (a cyclooxygenase inhibitor). Finally, the contractile response of iPF2alpha-III did not involve the release of thromboxane B2 and ET-1, measured using enzyme immunoassays. This study demonstrates that iPF2alpha-III is a vasoconstrictor of human saphenous veins, with a potency fourfold greater than that of PGF2alpha, and 50 times less than that of the thromboxane A2 mimetic, U46619. These effects are mediated at least in part by TP-receptor stimulation, but do not involve thromboxane A2 or ET-1 release.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Cyclosporine A and cremophor EL induce contractions of human saphenous vein: involvement of thromboxane A2 receptor-dependent pathway.

Chronic treatment with Sandimmune (cyclosporine A [CsA] dissolved in Cremophor EL [CrEL]) is often associated with hypertension and nephrotoxicity. The aims of the present study were to assess the effect of Sandimmune and its two main components (CsA and CrEL) on human saphenous veins and to study the underlying mechanism of their contractile responses. In organ bath, concentration-response curves for Sandimmune (36 ng/ml-120 microg/ml of CsA). CsA (36 ng/ml-120 microg/ml), or CrEL (2.4 microg/ml-8 mg/ml) were elicited in the presence of a thromboxane A2 (TXA2) receptor antagonist (GR32191, 0.3 microM), a cyclooxygenase inhibitor (indomethacin, 1 microM), a 5-lipoxygenase inhibitor (AA861, 10 microM), or their respective vehicles. In addition, the production of TXA2 after CsA challenge was assessed by enzyme immunoassay. Sandimmune, CsA, and CrEL induced concentration-dependent contractions on human saphenous veins. In terms of potency, CsA was a more potent vasoconstrictor agent than CrEL (EC50 values: 11.9+/-3.7 microg/ml (CsA, n = 12) vs. 1.2+/-0.4 mg/ml (CrEL, n = 16), p < 0.05). In contrast, in terms of efficacy, CrEL induced greater contractions than CsA (Emax (% of KCl 90 mM-induced contraction): 98.1+/-16.1% (CrEL, n = 16) vs. 17.0+/-4.3% (CsA, n = 12) p < 0.05). Pretreatment with GR32191 significantly reduced by 85% and 56% the contractions elicited by CsA and CrEL, respectively, whereas indomethacin had no effect. Finally, CsA (12 and 120 microg/ml) failed to stimulate TXA2 production. These in vitro data suggest that Sandimmune-induced contractions on human vascular smooth muscle appear to be mediated by CsA in the therapeutic ranges of doses and by both CsA and CrEL, which, in supratherapeutic doses, acted through a TXA2 receptor-dependent pathway.

Biphenyl Compounds↗
PubMed1999

Antagonistic effects of losartan on thromboxane A2-receptors in human isolated gastroepiploic artery and saphenous vein.

In addition to its AT1-receptor antagonist activity, losartan has been shown to antagonize thromboxane A2 (TXA2)-induced contraction of animal vessels. We investigated for the first time in human isolated gastroepiploic artery (GEA) and saphenous vein (SV) the TXA2/PGH2-receptor antagonist activity of losartan in the presence of indomethacin (1 microM) and N(omega)-nitro-L-arginine (100 microg). Losartan at concentrations of > or =1 microM on GEA and from 10 microM on SV significantly shifted U46619-induced contractions to the right. In addition, 100 microM losartan decreased by 34% the amplitude of the contraction to U46619 on both GEA and SV. The potency of losartan for the TXA2 receptor was 50- and 80-fold lower than that for the AT1 receptor on human GEA and SV, respectively. This inhibitory effect of losartan appeared selective for angiotensin II and TXA2-induced contractions because 100 microM losartan did not modify either endothelin-1- or KCl-induced contraction in human SV, although a reduction of norepinephrine- and 5-hydroxytryptamine-induced contraction was observed in human GEA and SV, respectively. In conclusion, losartan is an antagonist of TXA2 receptor on human GEA and SV. However, this antagonist activity occurred for a relative high dose of losartan, suggesting that it contributes at a low level, if any, to its antihypertensive effect.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Vasorelaxant actions of enoximone, dobutamine, and the combination on human arterial coronary bypass grafts.

Enoximone (a type III-selective phosphodiesterase inhibitor) and dobutamine (a beta-receptor agonist) are positive inotropic drugs frequently used in the postoperative management of coronary bypass surgery. The purpose of this study was to characterize their relaxant effects on the human internal mammary artery (IMA) and the gastroepiploic artery (GEA) and to test the hypothesis that their combination may have greater than additive relaxant effects. In organ baths, the relaxant effects of enoximone and dobutamine were tested on rings of IMA (n = 86) precontracted with U46619 (a thromboxane A2 mimetic), norepinephrine (NE), or KCl. The relaxant effects of dobutamine and enoximone also were tested on rings of GEA (n = 42) precontracted with U46619 and NE. The effect of the combination of enoximone and dobutamine were tested on rings of IMA (n = 24) precontracted with U46619 or NE. With respect to maximal relaxations induced by papaverine (10(-4) M), enoximone (< or =10(-3) M) caused full relaxations of IMA precontracted with NE, U46619, or KCI. Dobutamine (< or =10(-3) M) caused full relaxations of IMA precontracted with NE or KCI but only 46% (95% CI, 27-65) relaxation in the rings precontracted with U46619. Similar patterns of relaxation were observed in GEA rings, with dobutamine inducing partial relaxation in GEA precontracted with U46619. The pD2 values of enoximone and dobutamine were both significantly lower in segments precontracted with U46619. The in vitro threshold relaxant concentrations were in the upper limits or over the range of therapeutic plasma concentrations. The relaxant effect of the combination was significantly more important than the theoretic additive effect in IMA contracted with U46619 or NE. Enoximone and dobutamine are potent in vitro vasodilators but exert weak relaxant effects in IMA and GEA at concentrations in the therapeutic range. There is, however, a greater than additive vasorelaxant effect of the combination, suggesting that the vasorelaxant effect of the combination, in addition to the additive inotropic effect, may be beneficial to patients undergoing coronary bypass grafting.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Functional assessment of rat aorta after cold storage in different media.

Cold storage is frequently used to store isolated blood vessels for a limited period of time. However preservation of vascular smooth muscle and endothelial functions is time and medium-dependent. The present study was designed to compare the reactivity of rat aorta before and after cold storage for 24 and 48 h in one of four different solutions consisting of Hepes-buffered Krebs solution, Belzer solution, Krebs solution, and Eurocollins solution. Smooth muscle and endothelial functions of the rat aorta were assessed using in vitro isometric tension measurement. The results obtained for vessels preserved for 24 and 48 h were compared with those for vessels studied immediately after harvesting. Sensitivity and maximum contraction to KCl and norepinephrine were not altered in rat aorta preserved up to 48 h in Hepes-Krebs and Belzer solutions. In contrast, the amplitude of contraction elicited by KCl was significantly reduced by 50% and 77% in aorta stored for 24 and 48 h in Krebs solution and by 77% and 96% in those stored in Eurocollins solutions. Similarly, the maximal contraction elicited by norepinephrine was significantly reduced by 60% and 45% in arteries stored for 24 and 48 h in Krebs solution and by 34% and 86% in those stored in Eurocollins solution. In contrast, cold storage in the different media did not alter the relaxations elicited by sodium nitroprusside and forskolin. The endothelium-dependent relaxations in response to acetylcholine were not statistically modified after preservation up to 48 h in Hepes-Krebs solution. In contrast, the maximal relaxations to acetylcholine were significantly decreased after storage for 24 and 48 h in Belzer, Krebs and Eurocollins solutions. These results suggest that among the four media studied, Hepes-Krebs solution is the most suitable medium for the storage of blood vessels under hypothermic conditions.

Animals↗
PubMed1999

Functional comparison of the human isolated femoral artery, internal mammary artery, gastroepiploic artery, and saphenous vein.

Human femoral, internal mammary, and gastroepiploic arteries and saphenous veins are used as bypass grafts for coronary surgery or for reconstruction in arterial occlusive disease. We have characterized the contractile responses of these vessels to various agents that are liberated during cardiac or vascular surgery. In organ baths, U46619 (a stable thromboxane A2 mimetic), norepinephrine, endothelin-1, angiotensin II, and KCl caused concentration-dependent contractions in all vessels tested. Leukotriene C4 did not induce any contraction in the arteries, whereas a contraction was obtained in the saphenous vein rings. U46619 induced the most powerful contraction in all vessels tested. The pD2 values for each agent did not differ among the different vessels. When responses were expressed as a percentage of KCl-induced contraction, the contraction of endothelin-1 (151+/-5%) and leukotriene C4 (43+/-5%) was more significant on saphenous veins than on arteries. In conclusion, thromboxane A2 appears to be the most potent endogenous constricting agent on different human vascular beds. Our second finding is that saphenous veins are more sensitive to contract to leukotriene C4 and endothelin-1 than arteries. These properties may influence early and (or) long-term vein graft patency.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Are isoprostanes a clinical marker for antioxidant drug investigation?

Numerous pathological conditions are suspected to involve free radical production as part of their pathogenic process. Therefore, a pharmacological control of oxidative stress could probably benefit many vascular, inflammatory or degenerative diseases. However, the development of antioxidant drugs and their clinical evaluation are limited by the absence of an accurate, reliable and easy-to-handle marker of tissue oxidative events. Isoprostanes (isoPs), a prostaglandin-related series of metabolites, are emerging as major candidates for clinical measurement of oxidative stress. They are chemically stable products of lipid peroxidation, formed in cellular membranes and subsequently released and excreted in the urine. Many recent clinical studies have reported that urinary and plasma levels of isoPs (in particular the iPF2alpha-III isomer also called 8-epi-PGF2alpha) are increased in clinical conditions where oxidative stress is suspected to play a pathogenic role. Moreover, isoPs have been detected in tissue extracts from atherosclerotic plaques and Alzheimer patients brain tissue. Finally, antioxidant treatments such as vitamin E supplementation appear to reduce isoPs levels in biological fluids of treated patients. These preliminary observations argue for a further investigation of isoPs as a practical pharmacodynamic endpoint for the clinical evaluation of antioxidant therapies.

Antioxidants↗
PubMedDate not supplied

Vascular biology of the isoprostanes.

Isoprostanes are a family of compounds produced from polyunsaturated fatty acids via a free-radical-catalysed mechanism. F(2)-isoprostanes are prostaglandin F(2alpha) isomers derived from arachidonic acid. These compounds induce potent vasoconstriction, mediated primarily by TP receptor stimulation, and in some vessels by the release of cyclooxygenase products. This vasoconstriction may be modulated by the endothelium through the release of NO. Potent vasoconstriction is also observed with E(2)-isoprostanes. Experimental and clinical data suggest a role for F(2)-isoprostanes in atherogenesis. These compounds can be detected in free forms in biological fluids as well as esterified in low-density lipoproteins or cell membranes. Their quantification represents a reliable marker of lipid peroxidation. Elevated levels of F(2)-isoprostanes in biological fluids in pathological conditions including atherosclerosis, ischaemia-reperfusion injury, and inflammatory vascular diseases, suggest a relationship between lipid peroxidation and such diseases. F(2)-isoprostanes are currently being investigated as non-invasive quantitative markers to monitor the response to anti-oxidant treatment.

Dinoprost↗
PubMedDate not supplied

[In vitro study of of the effects of cysteinyl leukotrienes on human vascular preparations].

Leukotrienes are 5-lipoxygenase-derived arachidonic acid metabolites. In addition to their bronchoconstrictor effects, leukotrienes are also important modulators of the vascular tone which may exert paradoxical effects. Indeed, depending on the vascular tone (in either the basal or norepinephrine-precontracted state), leukotrienes are capable of inducing either contraction or relaxation. These paradoxical effects of leukotrienes depend on the vascular bed and the species investigated. Since urinary LTE4 excretion is increased in various cardiovascular diseases, including arterial pulmonary hypertension or cardiac ischaemia, the study of the effects of leukotrienes on human vascular preparations is of interest. This article reviews the in vitro evidence linking cysteinyl leukotrienes to the modulation of the vascular tone on human vascular preparations.

Blood Vessels↗
PubMedDate not supplied

[Leukotrienes and 12-HETE: key mediators of angiotensin II-mediated vascular effects.Rol in hypertension].

Arachidonic acid metabolism-derived products are key mediators of angiotensin II-mediated vascular effects. The modulatory effect of cyclooxygenase derived products--in particular thromboxane A2 and prostaglandin H2--in angiotensin II-mediated vascular effects is well established. In contrast, few studies have assessed the involvement of lipoxygenase-derived products in the vascular effects of angiotensin II. Cysteinyl leukotrienes (5-lipoxygenase-derived products) and 12-hydroxyeicosatetraenoic acids (12-HETE) (12-lipoxygenase-derived products) are potent proinflammatory and vasomotor mediators. Their biosynthesis is increased in various models of hypertension. In addition, compelling evidence has suggested that they might contribute to the vasoconstrictor, hypertrophic and mitogenic effects of angiotensin II. The demonstration of their contribution to angiotensin II-mediated vascular effects may explain, at least in part, the vascular inflammatory complications associated with hypertension.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗