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Biomedical subjects

U Pohl

Publications and source records attributed to U Pohl.

At least 109 records · Page 6Linked to original sources
PubMed1986

Crucial role of endothelium in the vasodilator response to increased flow in vivo.

Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.

Acetylcholine↗
PubMed1985

Effect of molsidomine on cardiac preload, coronary artery diameter, and coronary resistance.

The vascular and hemodynamic effects of a single intravenous bolus injection of molsidomine (100 micrograms/kg) were studied in six chronically instrumented, conscious dogs. At this dose only a minimal, short-term effect on peripheral resistance was observed. However, there was a pronounced dilation of peripheral veins and a simultaneous increase of effective vascular compliance of more than 60%. At the same time, central blood volume decreased significantly (17%). Because of preload reduction, left ventricular end-diastolic volume and pressure decreased significantly for more than 1 hour. A significant increase of large coronary artery diameter (up to 7% occurred simultaneously. Coronary resistance vessels were not affected. All effects reached a maximum between 15 and 30 minutes and were observed for at least 4 hours. We conclude that molsidomine exerts a long-lasting effect on the large coronary arteries and on the peripheral venous system. As a result of the combined effects on cardiac preload and on epicardial artery conductance, the myocardial oxygen supply and the supply/demand ratio will be improved.

Animals↗
PubMed1984

The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia.

The effect of intraluminal hypoxia on vascular tone and the release of prostaglandins (PG) I2 and E2 were investigated in intact isolated segments of canine femoral and coronary arteries as well as in the rat tail artery. Perfusion with hypoxic Tyrode's solution (pO2: 20-40 mm Hg) evoked a marked vasodilation of the segments, precontracted with norepinephrine or serotonin. Simultaneously, a 2-3-fold increase in the release of 6-keto-PGF1 alpha (the stable hydrolysis product of PGI2) could be observed. In parallel to 6-keto-PGF1 alpha, smaller quantities of PGE2 were released. Removal of the endothelium as well as pretreatment with indomethacin abolished both, the dilatory response and the PG-release. After administration of verapamil as well as 3,4,5-trimethoxybenzoic acid 8-diethylaminooctylester (TMB-8) (which binds intracellular calcium) the PG-increase was abolished and hypoxic dilatation could no longer be elicited, although the vessel had still a capacity to dilate. Exogenous administration of PGI2 and PGE2 showed that in canine femoral and coronary arteries PGI2 was the most effective vasodilating prostaglandin, while in the rat tail artery PGE2 had a 10-fold higher dilating potency compared to PGI2. At very high concentrations both PGI2 and PGE2 caused vasoconstriction. Our experiments suggest that the hypoxic endothelium-dependent dilatation may be mediated by an increased PG-release. Hypoxia-induced transmembrane calcium influx into the endothelial cells seems to be the trigger reaction.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Endothelial cells are involved in the vasodilatory response to hypoxia.

The role of endothelial cells in the dilatory response of arteries to hypoxia was studied in vitro using perfused arterial segments of rat and dog. The pO2 of the intra- and extraluminal perfusate could be varied separately. Intraluminal hypoxia (pO2 of 40 mmHg) induced a dilation irrespective of extraluminal pO2 level. On the contrary extraluminal hypoxia could not elicit a dilation during intraluminal normoxic perfusion. Dilation during extraluminal hypoxia could only be induced if the segment was not intraluminally perfused. The dilatory response to intraluminal hypoxia was abolished after enzymatical or mechanical removal of the endothelium. While theophylline and lipoxygenase inhibitors did not influence this endothelium-induced dilation, a significant reduction of the response could be observed after incubation with indomethacin. These results support the concept that prostacyclin (PGI2) might be involved in the hypoxic endothelium-induced dilation.

Acetylcholine↗
PubMed1978

[Hypothermic circulatory arrest after total blood exchange in dogs (author's transl)].

Total body washout (hct less than 1%) in hypothermia was performed in 31 dogs using either a crystalloidal or a colloidal perfusate. Blood exchange and cooling was achieved by means of partial bypass and heat exchanger. Short lasting blood exchange for crystalloids without cardiac arrest resulted in 66% survival of the animals. When in addition circulatory arrest was established for 30 min at 14 degrees C oesophageal temperature blood exchange for crystalloids was not tolerated. All four animals of this group died within 19 hours presenting massive interstitial edema. Replacement of the crystalloidal perfusate by a colloidal solution (2.5 g% Dextran 60 at Ringer's Lactate) and establishing circulatory for 30 or 60 min resulted in survival rates of 71% and 50% respectively. The use of the colloidal perfusate effectively prevented edema formation. Death could not be correlated with the parameters controlled.

Animals↗
PubMed1975

[Total blood exchange with circulatory arrest in deep hypothermia].

Total body wash out (hct less than 1%) with circulatory arrest of 30 to 60 minutes in deep hypothermia (esoph.temp. at 14 degrees C) was performed in 17 mongrel dogs by exchange against modified Ringer's Lactat-Solution. During rewarming the pump fluid was partly replaced by homologous packed red cells for readjustment of the hematocrit. After perfusion with a colloidfree perfusate all animals died under signs of massive interstitial edema. 8 out of 13 animals were long term survivors after exchange perfusion with colloid containing perfusate (dextran 60, 25 g/1). It has been demonstrated that a sanguineous circulatory arrest in deep hypothermia can be tolerated for 30 to 60 minutes if the formation of interstitial edema is prevented by use of an oncotically active perfusate.

Animals↗
PubMedDate not supplied

Opposing effects of nitric oxide on different connexins expressed in the vascular system.

Gap junctions--clusters of intercellular channels built by connexins (Cx)--are thought to be important for vascular cell functions such as differentiation, control of tone, or growth. In the vascular system, gap junctions can be formed by four different connexins (Cx37, Cx40, Cx43 and Cx45). The permeability of these connexin-formed gap junctions determines the amount of intercellular coupling and can be modulated by several vasoactive substances such as prostacyclin or nitric oxide (NO). We demonstrate here that NO has specific effects on certain connexins. Using two different techniques--injection of a fluorescent dye in single cells as well as detection of the de novo formation of gap junctions by a flow cytometry based technique--we found that NO decreases the functional coupling in Cx37 containing gap junctions whereas it increases the de novo formation of gap junctions containing Cx40. We conclude that NO, in addition to its known vasomotor effects, has a novel role in controlling intercellular coupling resulting in opposing effects depending on the specific connexin expressed in the cells.

Cell Communication↗
PubMedDate not supplied

Sensitive superoxide detection in vascular cells by the new chemiluminescence dye L-012.

The detection superoxide production in vascular cells is usually limited by a low sensitivity of available assays. We tested the applicability of the luminol derivate L-012 ¿8-amino-5-chloro-7-phenylpyridol¿3,4-dpyridazine-1,4(2H,3H)dione to measure superoxide production in cultured endothelial cells (human umbilical vein endothelial cells) and rat aortic segments. Following stimulation with the protein kinase stimulator phorbol 12-myristate 13-acetate (PMA, 1 microM) there was an 2.8-fold increase of L-012 chemiluminescence, whereas incubation with angiotensin II (100 nM) did not result in a measurable increase. Addition of vanadate (100 microM) considerably increased the chemiluminescence (up to 17-fold) after PMA and made possible the detection of an enhanced superoxide production after stimulation with angiotensin II (by 1.7-fold). This was due to a approximately 9-fold increase in signal intensity of L-012 in the presence of vanadate. Prolonged incubation with vanadate also led to a tyrosine phosphorylation-dependent increase in superoxide formation which was predominantly produced by an NAD(P)H oxidase. Short-term vanadate-enhanced L-012 chemiluminescence represents a highly sensitive assay making it possible to detect small changes of superoxide formation in intact vascular cells.

Coloring Agents↗
PubMedDate not supplied

Mediator role of prostaglandins in acetylcholine-induced vasodilation and control of resting vascular diameter in the hamster cremaster microcirculation in vivo.

Acetylcholine (ACh) is widely used as a standard test substance for nitric oxide (NO)-mediated vasodilation. However, it also augments the release of prostaglandins, a group of other endothelium-derived smooth muscle relaxants. Using intravital microscopy in the cremaster muscle of anesthetized hamsters, we studied the relative roles of NO and prostaglandins in mediating ACh-induced dilation and in the control of basal vessel tone (253 arterioles in 31 experiments) N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of NO synthase, significantly reduced ACh-induced vasodilation (by 42-73%), irrespective of whether it was applied intravenously (30 mg/kg) or topically (30 microM). Additional indomethacin (3 microM, topical) nearly abolished the dilator response. In contrast, the vascular responses to the endothelium-independent dilator sodium nitroprusside were not affected. The resting diameters (range: 6-114 microns) were significantly (p < 0.05) reduced after L-NNA or indomethacin by 10.2 and 16.6% of control diameter, respectively. The constriction induced by L-NNA was stronger in larger (> 50 microns) than in smaller (< 50 microns) vessels, whereas indomethacin was equipotent in both groups. Thus, in addition to NO, dilating prostaglandins are important mediators of the ACh-induced dilation and contribute to the control of resting arteriolar diameter in the hamster cremaster microcirculation in vivo.

Abdominal Muscles↗
PubMedDate not supplied

Irradiation induced clonogenic cell death of human malignant glioma cells does not require CD95/CD95L interactions.

BACKGROUND: Radiotherapy is the single most effective therapy for malignant gliomas. Targeting the CD95 apoptotic pathway is a promising experimental approach to these neoplasms. Here, we asked whether irradiation modulates CD95-mediated apoptosis of human malignant glioma cells in vitro. MATERIALS AND METHODS: LN-18, LN-229 and T98G human malignant glioma cell lines were irradiated with dosages from 0-8 Gy and treated with CD95L (CD95 ligand). CD95 expression was assessed by flow cytometry. Caspase activity was determined by DEVD cleavage. Cytotoxic effects were assessed by crystal violet staining of cells in a 96-well plate assay. Clonogenic cell death was determined by a standard colony forming assay. RESULTS: We find that (i) CD95L-induced apoptosis, but not irradiation-induced clonogenic cell death, involves caspase 3 activation and is blocked by the viral caspase inhibitor, crm-A. (ii) Irradiation does not modulate CD95 expression either in p53 wild-type or in p53 mutant glioma cell lines, and does not enhance CD95L-evoked caspase 3 activity or CD95L-induced clonogenic cell death. CONCLUSIONS: We conclude that endogenous CD95/CD95L interactions are not involved in radiation-induced clonogenic cell death and that the killing cascades of CD95L and irradiation are independent in human malignant glioma cells.

Apoptosis↗