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O Stücker

Publications and source records attributed to O Stücker.

12 recordsLinked to original sources
PubMed2000

Impact of serotonin on tumour growth.

Several opposite effects of serotonin (5HT) on tumour growth have been reported. On one hand, 5HT is known as a growth factor for several types of nontumoural cells, and it has been proposed to take part in the autocrine loops of growth factors contributing to cell proliferation in aggressive tumours such as small cell lung carcinoma. Depending on the tumour type either 5HT2 or 5HT1 receptor antagonist have been found to inhibit the 5HT-induced increase in tumour growth. In contrast, several authors have also reported that 5HT and 5HT2 agonist can inhibit tumour growth. Most often this effect has been considered to be related with the specific vasoconstrictive effect of 5HT or 5HT2 agonists on the vessels irrigating the tumour, which has been evidenced by intravital microscopy. Intravital microscopy studies have also shown that vessels perfusing the tumour exhibit a specific vasconstrictive response to 5HT1 agonists. In addition, 5HT has been shown to be involved in the effects of several anticancer treatments associated with the reduction of tumour flow. Finally, the specific vasoconstrictive effect of 5HT or 5HT receptor subtype agonists might also be useful in inducing hypoxia in tumours, which could be exploited in a strategy using hypoxia-selective cytotoxins or hypoxia-selective gene therapy.

Animals↗
PubMed1999

Role of endothelial factors in the specific response of mouse tumour-feeding arterioles to stimulation of 5-HT1 receptors.

PURPOSE: To investigate the possible role of endothelial mediators on the increased vasoconstriction to 5-HT1 receptor stimulation by the host-modified arterioles feeding a Meth-A tumour implanted in the flank of female Balb/c mice. MATERIALS AND METHODS: Using intravital microscopy, the response to the topical administration of the general 5-HT1 agonist 5-carboxamidotryptamine maleate (5-CT; 10(-6) M to 10(-4) M) by the tumour-feeding arterioles with the responses of tumour-independent arterioles and those of control arterioles from mice without tumour after antagonization or inhibition of the synthesis of endothelial mediators was compared. RESULTS: The dramatically higher vasoconstriction to 5-CT observed in tumour-feeding arterioles than in tumour-independent or control arterioles still persisted when either nitric oxide synthase, cyclooxygenase, lipoxygenase, or phospholipase A2 were inhibited or when thromboxane A2 or endothelin were antagonized. CONCLUSIONS: It was concluded that the higher reactivity to 5-HT1 stimulation by tumour-feeding arterioles is not due to changes in endothelial mediator release but probably due to changes affecting arteriolar smooth muscle.

Animals↗
PubMed1998

Characterization of the specific response to serotonin of mouse tumour-feeding arterioles.

PURPOSE: To investigate the role of tumour versus non-tumour factors in the specific response to serotonin (5-HT) of tumour-feeding arterioles (TFA). MATERIALS AND METHODS: Using mouse models of intra-vital microscopy, the response to topical administration of 5-HT was studied in arterioles feeding tumours: fibrosarcoma (Meth A), murine mammary adenocarcinoma (EMT6) and human colo-rectal carcinoma (HRT18) intra-cutaneously implanted. RESULTS: For all types of tumour, 5-HT induced a far more pronounced constriction of TFA than of control arterioles. The presence of a tumour implanted in the connective tissue between the skin and the cremaster muscle also affected the reactivity of muscle arterioles. Conversely, the response to serotonin by neovessels grown after implantation of an exogenous element under the skin did not differ from that of control arterioles. CONCLUSIONS: Changes in reactivity to serotonin were not dependent on the type of tumour implanted in the skin and were not present for a non-tumour implant. The presence of the tumour can alter the reactivity of vessels from tissue in contact with the tumour even if these vessels did not feed the tumour. This phenomenon is local and was not found in the vessels at a distance from the tumour.

Animals↗
PubMed1998

[Microcirculatory consequences of a venous striction in the rat. Effect of a coumarine-rutine association].

The aim of this study was to investigate the consequences of a venous striction on capillary red blood cell distribution and venular blood return and the effect of a coumarin derivative-rutoside combination. The study was conducted, in vivo, in the rat cremaster muscle using intravital microscopy. The striction lasted thirty minutes and was obtained by clamping the epigastric vein. This mechanical constraint was sufficient to induce microcirculatory modifications without disrupting microvessels. Before the striction (t-5 min), the velocities and diameters of the veins and arteries were comparable in all groups. After the striction (t5 min), in the control group, venous blood flow decreased by 60%, from 0.48 +/- 0.09 mm3/s (t-5 min) to 0.20 +/- 0.06 mm3/s (t5 min). The results showed that after thirty minutes reperfusion, venular blood flow in the control animals was only 34% of initial blood flow. The mean red blood cell velocity dropped by 56%, the percentage of low perfused capillaries increased from 7.5% to 50%. Treatment of animals with a coumarin derivative-rutoside combination, particularly at 4 mg/kg coumarin derivative-100 mg/kg rutoside, has significantly improved the microcirculation. After thirty minutes reperfusion venular blood flow was 60% and the percentage of low perfused capillaries was only 10%. The effect seemed to be more pronounced for rutoside than coumarin derivatives. The interest of this study was to set up an experimental model of a venous striction not too severe to induce micro-hemorrages but enough to modify microcirculation. This model was used to quantify the beneficial effects of a coumarin derivative-rutoside combination.

Animals↗
PubMed1997

Specific response of mouse tumor-feeding arterioles to stimulation by 5-HT1 agonists.

Using intravital microscopy, we compared the responses to 5-HT1 receptor stimulation by the host-modified arterioles feeding a Meth-A tumor implanted in the flank of female Balb/c mice with the responses of tumor-independent arterioles (TIA) and those of control arterioles from mice without tumor. Topical administration of 5 x 10(-5) M serotonin in the presence of 10(-4) M ketanserin (5-HT2 receptors inhibitor) induced arteriolar vasodilation in TIA (+13%) and in the control arterioles (+19%), but induced constriction (-14%) in the tumor-feeding arterioles (TFA). Topical administration of the general 5-HT1 agonist 5-carboxamidotryptamine maleate (10(-6) to 10(-4) M) or the 5-HT1A agonist buspirone (2 x 10(-6) to 2 x 10(-4) M) induced vasoconstriction that was dramatically higher in TFA than in TIA or control arterioles (p < 0.0001 in both cases). In addition, topical administration of the 5-HT1B agonist M-trifluoromethylphenylpiperazine (2 x 10(-6) to 2 x 10(-4) M) produced opposite responses, i.e., dose-dependent vasodilation in TIA and control arterioles, and dose-dependent constriction in TFA. Since we observed the same degree of vasodilation in response to 10(-4) M acetylcholine in all three groups of arterioles, the differences between the responses to 5-HT1 receptor stimulation were not due to the absence of endothelial-dependent dilatory mechanisms in the tumor-feeding arterioles. We conclude that 5-HT1 agonists are interesting pharmacologic tools for the modulation of tumoral blood flow, since they more dramatically constrict the microvasculature feeding the tumors than that feeding normal tissue.

Acetylcholine↗
PubMed1992

Specific esponse to 5-HT2 agonists by arterioles linked to Meth A tumors in mice.

Using intravital microscopy, we compared the responses to serotonin [5-hydroxytryptamine (5-HT)] and to a specific 5-HT2 agonist [1-(2,5-dimethoxy-4-bromo-phenyl)-2-aminopropane (DOB)] by normal arterioles and by the host-modified arterioles feeding a Meth A tumor implanted into the flank of female BALB/c mice. Topical and intravenous administration of 5-HT (10(-6) to 10(-4) M and 0.01-10 micrograms) or DOB (5 x 10(-7) to 5 x 10(-5) M and 0.01-10 micrograms) induced arteriolar constriction, which was far more pronounced for the arterioles feeding the tumor. This larger degree of vasoconstriction in tumor-feeding vs. normal arterioles was not found with norepinephrine. We also compared tumor growth and the mouse life span in three groups of mice, which were given 1 mg of serotonin or 0.74 mg DOB or saline solution. 5-HT or DOB both reduced tumor growth drastically compared with the controls (P less than 0.001), and survival rates were significantly higher in the 5-HT or DOB-treated groups (P less than 0.001). We conclude that 5-HT2-serotoninergic agonists are of particular pharmacological interest, since their vasoconstrictive action on the microvasculature feeding the tumors is much greater than in normal tissue and may interfere with tumor growth.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1985

Coronary response to large decreases of hemoglobin-O2 affinity in isolated rat heart.

In this study, the consequences of large increases of P50 (O2 partial pressure at 50% oxyhemoglobin saturation) on coronary blood flow (CBF) were investigated in isolated Wistar rat heart. Rightward shifts of the O2 dissociation curve (ODC), obtained by lysing and resealing erythrocytes to encapsulate inositol hexaphosphate (IHP), led to a very large increase in P50 without side effects. Each heart was perfused alternatively with control stored human blood [P50 = 18.8 +/- 0.3 (SE) mmHg] and IHP-treated human blood (P50 = 47.1 +/- 1.7 mmHg), according to the technique of Langendorff (mean perfusion pressure 80 mmHg; hematocrit 25%). Arterial PO2 of 180 mmHg was maintained to keep arterial O2 content identical for both types of blood. When hemoglobin affinity was lowered, CBF decreased from 5.32 +/- 0.20 to 3.40 +/- 0.14 ml X min-1 X g-1, coronary sinus PO2 (PcsO2) rose from 39.9 +/- 0.9 to 69.9 +/- 4.2 mmHg, and myocardial O2 consumption (MVO2) rose slightly from 0.125 +/- 0.005 to 0.149 +/- 0.010 ml O2 X min-1 X g-1 (P less than 0.05). A significant negative correlation was found between CBF and P50 (r = -0.90; n = 32) and a significant positive correlation between PcsO2 and P50 (r = +0.84; n = 28). The coronary blood flow response to high P50 values was not abolished when maximal dilation was induced by adenosine, so this response seems independent of metabolic needs. These experiments have demonstrated that if O2 uptake by erythrocytes remains constant, in the presence of a high P50, sufficient O2 supply may be achieved with substantially less blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1985

Effects of changes in hematocrit on red cell flows at capillary bifurcations.

A theoretical study was developed to evaluate effects of changes in hematocrit on red cell flow partitioning at narrow capillary bifurcations of unequal diameters. Non-Newtonian blood viscosity and non-linear relationships between blood and red cell flows at capillary bifurcations are taken into account. Results suggest that heterogeneity of diameters is a determinant of red cell and blood flows heterogeneity not only due to its influence on geometrical resistance but also as a result of its influence on capillary viscosity. Lowering hematocrit reduces differences in viscosities between the two branches. Then more homogeneous red cell flows are induced. Considering three possible relationships for entering blood flow vs. entering discharge hematocrit, the present study stresses that changes in red cell flow for individual capillaries are not parallel to changes in entering red cell flow. Therefore discussion on effects of hemodilution have to take into account not only red cell flow or oxygen arriving to an organ, but also changes in distribution of capillary flows induced by rheological changes due to lower hematocrit.

Blood Viscosity↗
PubMedDate not supplied

Effects of Ginkgo biloba extract (EGb 761) on arteriolar spasm in a rat cremaster muscle preparation.

The effects of an extract of Ginkgo biloba (EGb 761) on arteriolar spasm were confirmed using a preparation of rat cremaster muscle. When vasospasm was induced by rat serum, arteriolar constriction reached 25-30% of the initial diameter after 10 min. Intravenous injection of EGb 761 (30 mg/kg) 5 min after inducing spasm inhibited about 80% of this serum-induced vasoconstriction. As previous studies have shown that EGb 761 has an antiaggregatory effect on platelets, thrombin, serotonin (platelet-derived compounds that are present in the serum) and a thromboxane analogue (U46619) were also used to induce vasospasm. Administration of EGb 761 (30 mg/kg) 5 min after exposure of the preparation to serotonin (10(-3) M) or 10 min after exposure to thrombin (20 units) did not affect vasospasm induced by these agents. In contrast, treatment with this same dose of EGb 761 5 min after exposure of the preparation to U46619 (10(-4) M) abolished the arteriolar constriction induced by this agent in 15 min. The thromboxane/prostaglandin H2 receptor antagonist SQ29548 antagonized serum-induced vasospasm, indicating an involvement of thromboxane. Other experiments indicated that the effects of EGb 761 of counteracting vasospasm may be mediated in part by ginkgolide B, a triterpene constituent of the extract that is an antagonist of platelet-activating factor and in part by an 'NO-like' action of its proanthocyanidin constituents. Taken together, these results have revealed that EGb 761 treatment can antagonize the vasoconstrictor effect of thromboxane on arterioles. As thromboxane is implicated in many cardiovascular disorders, this property of EGb 761 may explain some of its beneficial clinical effects in such pathologies.

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

Effect of Ginkgo biloba extract (EGb 761) on the vasospastic response of mouse cutaneous arterioles to platelet activation.

The effect of intravenously administered Ginkbo biloba extract (EGb 761) on the vasospastic response to platelet activation has been assessed using a cutaneous flap preparation in anaesthetized mice. Arterioles of the axillary artery were observed by intravital microscopy, and platelets were activated by topical application of ADP under two steady state conditions: normothermia (37 degrees C) and hypothermia (24 degrees C). Responses of the cutaneous arterioles to stimulation by topical application of a thromboxane agonist (U46619) were also compared in animals treated intravenously with EGb 761 or with a thromboxane synthesis inhibitor (U63557). ADP induced a 34% constriction of the arterioles in control animals. However, no arteriolar constriction occurred in response to ADP in platelet-depleted animals (collagen-induced thrombocytopenia) or in animals treated with EGb 761 (60 mg/kg, i.v.). Exposure of the arterioles to hypothermia (24 degrees C) for 10 min induced constriction of 7-12% in all experimental groups of animals. Under these hypothermic conditions, either EGb 761 or thrombocytopenia abolished ADP-induced arteriolar constriction which was substituted by arteriolar dilation, indicating that EGb 761 can inhibit the vasospasm that is produced by platelet activation. As topically applied U46619 (10(-5) M) induced arterioles constriction (about 22%) that was abolished by intravenous treatment with EGb 761, the extract appears to act directly rather than as a thromboxane synthase inhibitor. Collectively, these findings indicate that platelet factors can play a significant role in cutaneous vasospasm, and that EGb 761, via an action on the thromboxane pathway, could be useful in treating Raynaud's phenomenon and other vascular disorders which involve increased thromboxane production.

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