Biomedical subjects

M Wahl

Publications and source records attributed to M Wahl.

At least 55 records · Page 3Linked to original sources

PubMed1998

Endothelin-1-induced contraction in cerebral vessels mediated by phospholipase C/protein kinase C cascade.

Endothelin (ET) vasoconstricts cerebral vessels potently, an effect mediated by ET(A) receptors on the smooth muscle, although the subsequent signaling cascade is unclear. We tested whether the action of ET-1 is mediated by the phospholipase C (PLC)/protein kinase C (PKC) cascade. Isometric force was measured in vitro in ring segments of rat basilar (BA) and middle cerebral (MCA) arteries and expressed as a percentage of the contraction to 124 mM K+. Concentration-effect curves for the constrictor effect of ET-1 (1 pM = 0.3 microM) in control segments or after 25 minutes preincubation with an inhibitor of PLC (neomycin 100 microM) or PKC (H7 10 microM) were constructed under resting tone. In untreated BA, 100 nM ET-1 induced a contraction of 119 +/- 5.3% that fell significantly to 97 +/- 2.8% and 98 +/- 6.7% after neomycin or H7 pretreatment, respectively. In MCA, 100 nM ET-1 induced a contraction of 105 +/- 3.2% that fell significantly to 93 +/- 6.3% and 64 +/- 8.1% after neomycin or H7, respectively. There was no significant shift of the ET-1 EC50 after PKC inhibition in either vessel or PLC inhibition in BA. In summary, the amplitude of ET-1-induced contraction in cerebral vessels is reduced significantly, whereas the sensitivity to the agonist is unchanged, after blocking PLC with neomycin or PKC with H7. This indicates noncompetitive inhibition. ET-1-induced contraction in cerebral vessels thus depends on activation of the PLC/PKC cascade.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Dilator effect of bradykinin and acetylcholine in cerebral vessels after brain lesion.

Vasodilation elicited by bradykinin (BK) or acetylcholine (Ach) (10 nM-10 microM) in isolated rat cerebral arteries was studied under control conditions, after sham treatment, and after cold lesion (placing a cooled metal probe on the exposed dura) of the cortex. After 24 or 48 hours, isometric force was measured in ring segments of basilar (BA) and middle cerebral arteries (MCA). Concentration-effect curves were constructed after precontraction with 100 microM uridine triphosphate (MCA) or 1 microM serotonin (BA). In MCA and BA, BK elicited similar relative relaxations with maxima of 40.9 +/- 1.5% and 40.7 +/- 3.1%, respectively, at 1 microM. Ach-induced relaxation in BA was much stronger with 82.0 +/- 5.8% at 1 microM. MCA did not relax consistently to Ach. Relaxation to BK in MCA segments was not different between sham-treated and untreated animals. After cold lesion, the dilation to BK (1 microM) was significantly reduced at 24 hours from 0.7 +/- 0.06 to 0.4 +/- 0.06 mN. At 48 hours, this decrease was partly reversed (to 0.5 +/- 0.07 mN). In BA, there was no difference in Ach-induced relaxation between cold-lesioned or sham-treated animals. In summary, the nitric oxide (NO)-mediated response to BK in MCA is attenuated 24 hours after cold lesion. This damage to the BK/NO system is partly reversed 48 hours after the lesion.

Acetylcholine↗

PubMed1998

Reduced reactivity of the middle cerebral artery and its large branches after cold lesion.

The aim of this study was to measure vascular reactivity in the isolated middle cerebral artery (MCA) after brain injury. Segments of MCA were prepared from control, sham-operated, and cold-lesioned rats. Cold lesion was induced by application of a precooled (-78 degrees C) copper cylinder (diameter 5 mm) for 60 sec to the intact dura over the parietal cortex. Endothelin-1 (ET-1) (10(-12) to 3 x 10(-7) M) induced a dose-dependent contraction with a pD2 (-log10 EC50) of 8.36+/-0.12 (mean+/-SEM) and an Emax (maximal response) of 2.41+/-0.15 mN (millinewton) at 10(-7) M in sham-operated animals under resting conditions. This maximum contraction induced by 10(-7) M ET-1 was significantly (p < 0.05) reduced 24 and 48 h after cold lesion by 41% and 30%, respectively. After precontraction with 10(-5) M prostaglandin (PG) F2alpha, ET-3 (10(-12) to 10(-8) M) relaxed the MCA with an Emax of 0.42+/-0.07 mN at 10(-8) M and a pD2 of 9.20+/-0.19 in sham-operated animals. This relaxation was reduced 24 and 48 h after cold lesion by 19% and 62% at 10(-8) M, respectively. Concentration-effect curves for bradykinin (BK, 10(-8) to 10(-5) M) in uridine triphosphate (UTP, 10(-4) M)-precontracted MCA segments revealed relaxation with a pD2 of 7.08+/-0.10 and an Emax of 0.65+/-0.06 mN at 10(-6) M in sham-treated animals. This effect of BK was reduced by 35% and 20% at 10(-6) M 24 and 48 h after cold lesion, respectively. In addition, the contractile responses to 124 mM K+, 10(-5) M PGF2alpha and the dilation induced by 10(-3) sodium nitroprusside (SNP) were reduced in MCA segments taken 24 and 48 h after lesion compared with shams. We conclude that attenuation of ET effects can be explained, at least in part, by tachyphylaxis to ETs. The unspecific reduction of vascular reactivity may result from spreading depression.

Animals↗

PubMed1998

Involvement of thromboxane A2 in the mediation of the contractile effect induced by inhibition of nitric oxide synthesis in isolated rat middle cerebral arteries.

Inhibition of nitric oxide (NO) synthesis induces vasoconstriction and reduction of the blood flow in the brain, indicating that basal release of NO provides a resting vasorelaxant tone in the cerebral circulation. In the present study, the contractile effect of the NO synthase blocker NG-nitro-L-arginine (100 mumol/L) in isolated rat middle cerebral arteries was attenuated markedly in the presence of the cyclooxygenase inhibitor indomethacin (5 mumol/L), the thromboxane A2 synthase inhibitor ridogrel (10 mumol/L), or the thromboxane receptor antagonist ICI 192605 (100 mumol/L). These results indicate that removal of the endogenous NO stimulates the release of thromboxane A2 in cerebral vessels and basal NO production regulates the resting cerebrovascular tone, at least in part, by suppressing thromboxane A2.

Animals↗

PubMed1998

Delayed loss of ETB receptor-mediated vasorelaxation after cold lesion of the rat parietal cortex.

The aim of this study was to investigate the involvement of endothelins (ET) in brain injury. The effect of ET was studied in the isolated basilar artery (BA) taken from control, sham-operated, and cold-lesioned rats. Cold lesion was induced by application of a precooled (-78 degrees C) copper cylinder (outer diameter 5 mm) for 60 seconds to the intact dura over the parietal cortex. After precontraction with prostaglandin (PG) F2alpha, ET-3 (10(-10) to 10(-8) mol/L) dilated BA with a pD2 (negative log of the half-maximal concentration) of 9.06+/-0.031 (mean +/- SD) and a maximal effect (Emax) of 1.64+/-1.0 mN at 3 x 10(-9) mol/L in sham-operated animals. This dilation was reduced 24 and 48 hours after cold lesion by 33% and 73%, respectively, at 3 x 10(-9) mol/L. The effects of acetylcholine (10(-8) to 10(-4) mol/L) and sodium nitroprusside (10(-3) mol/L) were unaltered. Activation of the ETB receptor in thoracic aorta by the specific agonist IRL 1620 also resulted in a reduced dilation (51% by 48 hours after cold lesion). Reverse transcriptase-polymerase chain reaction of the BA showed unaltered expression of mRNA for the ETB receptor after cold lesion whereas ETB immunoreactivity in BA and in its intraparenchymal arteries was reduced at 24 and 48 hours. In contrast to the reduction of ET-3-induced dilation, the constrictor effects of ET-1 and ET-3 were retained after cold lesion. Endothelin-1 (10(-12) to 10(-6) mol/L) dose-dependently contracted segments of untreated control BA segments under resting conditions with a pD2 of 8.03+/-0.22 and an Emax of 6.35+/-0.70 mN. Further evidence that the constrictor ability of BA was not influenced by cold lesion is given by the unaltered response to 124 mmol/L K+ and 10(-6) mol/L serotonin. We conclude that the ETB receptor of BA after cold lesion is downregulated specifically, apparently at the posttranscriptional level. Because the ETB-mediated dilation in thoracic aorta was also reduced, downregulation of the ETB receptor apparently is not restricted to cerebral arteries. The nitric oxide-cyclic guanosine monophosphate system in BA is, however, intact.

Animals↗

PubMed1997

Endothelium-dependent relaxation counteracting the contractile action of endothelin-1 is partly due to ETB receptor activation.

The vasomotor effects of the endothelins (ETs) are mediated by activation of receptor subtypes termed ETA and ETB. The present study aimed to characterize the interaction of ETA and ETB receptor activation in the cerebral circulation. Ring segments obtained from rat basilar artery were used for measurement of isometric force under resting tension or following precontraction with prostaglandin F2 alpha. In some segments, the endothelium was removed mechanically. In precontracted arteries, ET-1 elicited contraction only. In the presence of the ETA receptor antagonist, BQ-123 (10(-5) M), however, ET-1 induced a concentration-related relaxation with a pD2 value of 8.93 +/- 0.16 (mean +/- SEM, n = 15). The relaxant action was abolished following preincubation with an ETB receptor antagonist, IRL-1038 (3 x 10(-6) M), or with a nitric oxide synthase inhibitor, NG-nitro-L-arginine (10(-5) M). These results indicate that the relaxation was mediated by ETB receptor activation coupled to the release of nitric oxide. Under resting tension, ET-1 elicited concentration-related contraction (pD2: 8.03 +/- 0.04, n = 37). In arteries devoid of a functional endothelium, the concentration-effect curve was shifted to the left yielding a pD2 value of 8.88 +/- 0.11 (n = 31). Similarly, in endothelium-intact arteries contraction to ET-1 was augmented following nitric oxide synthase inhibition or ETB receptor blockade with 3 x 10(-6) M BQ-788 (pD2: 8.94 +/- 0.18, n = 19). The results suggested that, in the isolated rat basilar artery, ET-1 induced coactivation of the contraction-mediating ETA receptor and the relaxation-mediating ETB receptor. The coactivation resulted in opposing vasomotor effects, but the contraction covered relaxation under normal conditions. However, force development by ET-1 was suppressed by its endothelium-dependent relaxant action.

Animals↗

PubMed1997

Mediation of endothelium-dependent relaxation: different response patterns in rat and rabbit basilar artery.

The endothelial lining of blood vessels plays an important role in the control of arterial tone by releasing a number of vasoactive factors. Among these, nitric oxide (NO) or a NO containing moiety, some cyclooxygenase products such as prostacyclin (PGl2) and a still hypothetical hyperpolarizing factor may induce dilatation/relaxation. In the present study, the functional importance of these factors in mediating endothelium-dependent relaxation has been investigated in isolated cerebral arteries. Acetylcholine (ACh) was used to induce endothelium-dependent relaxation of ring segments obtained from rat and rabbit basilar artery (BA). Glibenclamide (10(-6) M) which acts as an inhibitor of ATP-sensitive K+ channel activation did not affect the relaxant action of ACh. With the cyclooxygenase blocked by indomethacin (10(-6) M) ACh-induced relaxation was unaffected in rat BA and only slightly attenuated in rabbit BA. The NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 10(-6) and 10(-5) M) completely abolished ACh-induced relaxation in rat BA and resulted in a moderate inhibition in rabbit BA (10(-5) and 10(-4) M). However, ACh-induced relaxation of rabbit BA was abolished in the presence of both indomethacin and L-NNA. These results indicate that endothelium-dependent relaxation of large cerebral arteries is mediated by NO acting alone or in concert with a relaxant cyclooxygenase product. In addition, there is no indication for the action of an endothelium-derived hyperpolarizing factor different from NO or a prostanoid.

Acetylcholine↗

PubMed1997

[Not Available].

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Greek World↗

PubMed1997

Brain edema: pathogenesis and therapy.

In the brain intravascular and interstitial spaces are separated by a highly specialized endothelial lining, which is the morphological substrate of the blood-brain barrier (BBB). Under physiological conditions the BBB exerts rigid control of water soluble compounds moving from blood into brain and from brain into blood, respectively. Under pathological conditions such as trauma or ischemia, an increase in BBB permeability may occur that allows plasma constituents to escape into the brain tissue. This "opening" of the BBB may, at least in part, be due to a massive release of autacoids, which thus act as mediators of vasogenic brain edema. Five criteria have to be fulfilled by a given autacoid to be considered a mediator candidate: (i) a permeability-enhancing action under physiological conditions; (ii) a vasodilatory action; (iii) the ability of inducing vasogenic brain edema; (iv) an increase of concentration in tissue or interstitial fluid under pathological conditions; and (v) a decrease of brain edema by inhibiting the release or action of a given autacoid. Among the mediator candidates discussed, only bradykinin fulfills all these criteria. Histamine, arachidonic acid and free radicals, including nitric oxide, may also be considered mediator candidates of brain edema, but for each of these compounds evidence is less clear than for bradykinin. Although the concept of autacoids mediating brain edema is well established and supported by experimental data, it has not yet gained entrance into the clinics. Treatment of patients suffering from vasogenic brain edema is symptomatic and mainly concentrated on the control of intracranial pressure.

Arachidonic Acid↗

PubMed1996

Vasomotor and permeability effects of bradykinin in the cerebral microcirculation.

All components of an intracerebral kallikrein-kinin system have been described. Thus, bradykinin (BK) acting from the parenchymal site as well as from the blood site may influence cerebral microcirculation. BK is a potent dilator of extra- and intraparenchymal cerebral arteries when acting from the perivascular site. The vasomotor effect of BK is mediated by B2 receptors which appear to be located at the abluminal membrane of the endothelial cell. The effect of BK is mediated by NO. prostanoids, free radicals, H2O2 or leukotrienes depending on the animal species and on the location of the artery. Selective opening of the blood-brain barrier for small tracers (Na(+)-fluorescein; MW, 376) has been found in cats during cortical superfusion or intraarterial application of BK. This leakage is mediated by B2 receptors located at the luminal and abluminal membrane of the endothelial cells. Formation of brain edema has been found after ventriculo-cisternal perfusion or interstitial infusion of BK. This can be explained by increase of vascular permeability and cerebral blood flow due to arterial dilation thus enhancing driving forces for the extravasation. An increase of the BK concentration in the interstitial space of the brain up to concentrations which induce extravasation, dilatation and oedema formation has been found under several pathological conditions. Thus, BK may be involved in oedema formation after cold lesion, concussive brain injury, traumatic spinal cord and ischemic brain injury. The mediator role of BK in brain edema is further supported by therapeutic results. Brain swelling due to cold lesion or ischemia could be diminished by treatment with kallikrein-inhibitors. Similarly, dilatation of cerebral arterioles after concussive brain injury was reduced by blockade of B2 receptors. Thus, all criteria favour BK as one mediator of vasogenic oedema.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Intravenous beta-endorphin administration fails to alter hypothalamic blood flow in rats expressing normal or reduced nitric oxide synthase activity.

beta-Endorphin (beta-END) significantly contributes to the maintenance of hypothalamic blood flow (HBF) autoregulation during hemorrhagic hypotension in rats. Recently, several natural and synthetic opioid peptides were reported to induce nitric oxide (NO)-mediated dilation in the cerebrovascular bed. In the present study, the effect of beta-END was studied on HBF and hypothalamic vascular resistance (HVR) in vehicle-treated control rats and in rats after the pharmacological inhibition of the NO synthesis by chronic oral application of NG-nitro-L-arginine methyl ester. Intravenous beta-END administration failed to alter HBF or HVR either in control or in NO-blocked animals, and its transient hypotensive effect was not inhibited by NO blockade, indicating that beta-END may not have NO-mediated vasodilator effect in the hypothalamic or in the systemic circulation.

Animals↗

PubMed1996

Bradykinin dilates rat middle cerebral artery and its large branches via endothelial B2 receptors and release of nitric oxide.

Ring segments of rat middle cerebral artery (MCA) were prepared for measurement of isometric force and precontracted with 10(-4) M uridine triphosphate (UTP). Concentration-effect curves (CEC) were constructed for bradykinin (BK, 10(-8)(-10)(-1) M) in segments with functionally intact (E+) or denuded (E-) endothelium. E- segments did not dilate to BK. The BK receptor was characterized by application of specific B1 or B2 antagonists [des-Arg4-Leu8] BK (10(-5) M) and [D-Arg4-Hyp3-Thi5-D-Tic7-Oic8] BK (HOE140, 3 x 10(-7) M), respectively, or B2 agonist [des-Arg9] BK (10(-8)-10(-4) M). Involvement of nitric oxide (NO) was tested with NG-nitro-L-arginine (LNNA, 10(-4) M). BK induced concentration-dependent relaxation with a maximal effect (Emax) of 40.86 +/- 1.50% at 10(-4) M and a pD2 (-log10 EC50) of 6.818 +/- 0.044. This relaxation could be prevented with HOE140 or LNNA, but was not influenced by [des-Arg(9)-Leu] BK. [des-Arg9] BK did not induce any effect. These results demonstrate that BK induced relaxation via endothelial B2 receptors and release of NO in isolated rat MCA.

Animals↗

PubMed1996

Cerebrovascular effects of endothelin-3: modulation of contraction by nitric oxide is independent of endothelin B receptor activation.

In cerebral arteries, endothelin (ET)-3 induces relaxation in a low concentration range by activating ETB receptors located on the endothelium and, at higher concentrations, contraction by activating ETA receptors located on smooth muscle cells. The interaction of these receptors has been investigated in the present study by measuring isometric force in ring segments of basilar arteries obtained from male normotensive rats. In precontracted arteries, the ETA receptor antagonist BQ-123 markedly enhanced the relaxant effect of ET-3, while the ETB receptor antagonist BQ-788 appeared to exert a competitive antagonism. Under resting tension, the contractile action of ET-3 was enhanced following nitric oxide synthase inhibition and endothelium denudation but not in the presence of ETB receptor antagonists. These results suggest i. the relaxant effect of ET-3 is decreased by ETA receptor activation, ii. a functionally intact endothelium shifts the contractile action of ET-3 towards higher concentrations, and iii. the inhibitory effect of the endothelium on ET-3 induced contraction is independent of ETB receptor activation. The main action of ET-3 in the cerebral circulation thus appears to be relaxant, and blockade of this effect may not be desirable in pathological conditions in which the release of ET-3 is increased.

Animals↗

PubMed1996

Quantitative detection of human immunodeficiency virus (HIV) antigen by the Enzymun-Test: comparison with alternative assays and nucleic acid sequence-based amplification of HIV type 1 RNA.

A new modular automated enzyme immunoassay (EIA) (Enzymun-Test HIV Ag: Boehringer Mannheim) for quantitative human immunodeficiency virus (HIV) antigen detection was evaluated by testing a panel of 1,506 serum samples, including seroconversions, dilution series, follow-up samples from patients under antiretroviral therapy, single serum specimens from HIV-seropositive individuals in different stages of infection, potentially cross-reactive samples, and sera from HIV-negative hospitalized patients. The Abbott HIV type 1 (HIV-1) antigen monoclonal antibody assay served as the reference assay, and nucleic acid sequence-based amplification (Organon Teknika) for quantitative amplification of HIV-1 RNA was used for follow-up of patients under antiretroviral chemotherapy. The Boehringer Mannheim and Abbott EIAs showed concordant results for the early detection of HIV antigen in all the seroconversion panels. The follow-up samples from 29 HIV-infected individuals under antiretroviral therapy gave divergent results between both antigen tests. For the detection of HIV antigen in single serum samples from HIV-infected patients in different stages of HIV infection, a higher number of positive samples was detected with the Abbott HIV-1 antigen monoclonal antibody assay in samples from patients in stages II and III of HIV infection. The Enzymun-Test detected three or more positive samples than did the Abbott assay among the samples of patients with AIDS. The concordance on a sample-to-sample basis between the Boehringer Mannheim and Abbott EIAs was 98.6%. The sensitivity of the Enzymun-Test in comparison to the reference assay was 97.2%; the specificity was 98.8%. Although no close correlation could be found between the amount of viral RNA in serum detected by nucleic acid sequence-based amplification and the concentration of HIV antigen, a high HIV-1 RNA copy number was mostly associated with high levels of HIV antigen. In conclusion, the Enzymun-Test permits accurate HIV antigen detection and offers, in contrast to previous assays, the possibility of completely automated detection.

AIDS Serodiagnosis↗

PubMed1996

Oral empiric treatment of community-acquired pneumonia. A multicenter, double-blind, randomized study comparing sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group.

STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin (Spfx) vs roxithromycin (ROXI) for treatment of community-acquired pneumonia (CAP). DESIGN: Multicenter, double-blind, randomized study. SETTING: Twenty-three university and community hospitals in Scandinavia. PATIENTS: Three hundred four adults (> or = 18 years of age) with CAP treated as outpatients (25%) or inpatients (75%). INTERVENTIONS: Randomization 1:1 to Spfx, 400 mg on day 1, then 200 mg once daily, or ROXI, 150 mg twice daily, 10 to 14 days. Safety and efficacy analyses in intention-to-treat (ITT) and evaluable populations. RESULTS: Three hundred three of 304 patients were included in the ITT and safety analyses and 260 (86%) were evaluable at the end of follow-up. Streptococcus pneumoniae was the cause of pneumonia in 62 (20%) patients (11 with bacteremia), Chlamydia pneumoniae in 40 (13%), and Mycoplasma pneumoniae in 38 (13%) patients. The success rates for Spfx and ROXI at the end of follow-up were 82% and 72%, respectively, in the ITT population, and 94% and 79%, respectively, in the evaluable population. The odds ratio Spfx/ROXI for success was 4.5 (95% confidence interval, 1.9, 10.8) for the evaluable population. Both drugs were, overall, equally safe. GI symptoms were the most common adverse experiences in both groups. Prolongation of QTc, without clinical symptoms, was seen in 3% of Spfx patients and in 1% of ROXI patients, and photosensitivity, mostly mild to moderate, was seen in 5% of the Spfx group. CONCLUSIONS: Oral treatment with Spfx was superior to ROXI for the treatment of moderately severe CAP. Spfx was effective for all isolated pathogens, including S pneumoniae, and may be an alternative for empiric treatment of CAP, especially in areas with a high incidence of beta-lactam-resistant pneumococci.

Administration, Oral↗

PubMed1996

Opiate receptor-mediated mechanisms in the regulation of cerebral blood flow.

Endogenous opioid peptides are present in cerebral perivascular nerves and in the CSF, and their concentrations are changing in response to stimuli that activate regulatory mechanisms of the cerebral circulation (e.g., alterations of the perfusion pressure or changes of the arterial O2 tension). Opiate receptors are expressed in the cells of the CNS and the cerebrovascular bed, and their activation modulates the function of other vasoregulatory mechanisms (i.e., the autonomic nervous system, nitric oxide, prostanoids, vasopressin) that are involved in the control of the cerebrovascular tone. The direct vasomotor effects of opioid peptides and opiates on the cerebral arteries under in vitro or in situ conditions appear to be weak or absent in several species. However, Met- and Leu-enkephalin induce pial arterial vasodilation in the newborn pig. In this species, beta-endorphin acts as a constrictor, whereas dynorphin may induce either dilation or constriction depending on the experimental conditions. The influence of exogenously applied natural and synthetic opioids on the cerebral blood flow (CBF) is determined mainly by their metabolic, neuronal, and respiratory effects. Hypothalamic and pituitary circulations are especially sensitive to opioids. Under resting conditions, endogenous opioid peptides do not participate in the regulation of the cerebrovascular tone and CBF. On the other hand, mu and delta opiate receptor stimulation by endogenous opioid peptides, interacting with other vasoactive factors, obviously contributes to the hypoxia- and hypercapnia-induced cerebral vasodilation. Furthermore, endogenous opioid mechanisms are involved in the autoregulation of the hypothalamic blood flow. Thus, the endogenous opioid system may well represent a latent regulatory mechanism, which is of limited importance under basal conditions, but becomes more important under conditions of stress. Synthetic exogenous opioids do not appear to influence the hypoxic or hypercapnic CBF responses or the cerebral autoregulatory process.

Brain Chemistry↗

PubMed1995

Relative elemental sensitivity factors in non-resonant laser-SNMS.

Using a reflectron time-of-flight mass spectrometer, the ionization process in non-resonant Laser postionization Secondary Neutral Mass Spectrometry (SNMS) has been investigated. In particular, the postionization efficiencies (PIE) achieved by multi photon and single photon absorption have been compared by ionizing ten elements sputtered from a NIST standard reference material by excimer laser radiation of 248 nm, 193 nm and 157 nm. Only in the case of single photon ionization (SPI) the measured laser intensity dependence of the PIE can be understood quantitatively in terms of corresponding theory. From the results, absolute values of the SPI cross sections have been evaluated for atoms of nine elements, which show a total variation over about two orders of magnitude. Furthermore, even in the regime of high laser intensity, where the ionization of all atoms is completely saturated, different elements have been detected with relative sensitivity factors which scatter over about one order of magnitude. This has been attributed to element dependent variations of the effective ionization volume which are caused by the different kinetic energy and angular distributions of different sputtered atoms.

Journal Article↗

PubMed1995

Endothelin-3-induced relaxation of isolated rat basilar artery is mediated by an endothelial ETB-type endothelin receptor.

The endothelin (ET) receptor mediating relaxation of cerebral arteries was characterized using ring segments obtained from the rat basilar artery. Under resting tension, ET-3 (> 10(-8) M) but not the specific ETB receptor agonist IRL 1620 induced contraction. In ring segments precontracted with 3 x 10(-6) M prostaglandin (PG) F2 alpha, ET-3 (10(-12) - 10(-8) M) and IRL 1620 (10(-14) - 10(-6) M) induced concentration-related relaxation. IRL 1620 was more potent than ET-3, the pD2 (-log10EC50) values being 10.002 +/- 0.751 (mean +/- SD) for IRL 1620 and 8.836 +/- 0.415 for ET-3. Relaxation was abolished after preincubation with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (10(-5) M) as well as in segments devoid of a functionally intact endothelium. At a concentration above 10(-8) M, ET-3 resulted in a further increase of PGF2 alpha-induced contraction that was not observed with IRL 1620. The presumably specific ETB receptor antagonist IRL 1038 (10(-7) - 3 x 10(-6) M) diminished or even abolished (3 x 10(-6) M) the relaxation induced by ET-3 or IRL 1620. IRL 1038 did not exert any vasomotor effect by itself, and it did not significantly affect ET-3-induced contraction. These results indicate that in the rat isolated basilar artery, the ET-3-induced relaxation is probably due to activation of an ETB-type receptor located on the endothelial cells and mediated by release of nitric oxide.

Acetylcholine↗