Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MEDIATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1984

Adenosine receptors mediating inhibitory electrophysiological responses in rat hippocampus are different from receptors mediating cyclic AMP accumulation.

Electrophysiological and biochemical techniques were used to characterize adenosine receptors in rat hippocampus. The site which mediates the inhibitory action of adenosine on excitatory synaptic transmission and on spontaneous interictal spiking had properties similar to the adenosine A1 receptor. Thus, the relative order of potency for adenosine analogs was L-PIA greater than or equal to CHA greater than NECA greater than 2CA (L-PIA = N6-phenylisopropyladenosine; CHA = N6-cyclohexyl-adenosine; NECA = adenosine 5'-ethylcarboxamide; 2CA = 2-chloroadenosine), with EC50 values for the most potent analogs between 10-30 nM. The effect of the stable adenosine analog, particularly CHA and L-PIA, was slow in onset and very slowly reversible. This is suggested to be due both to a slow dissociation of these compounds from the receptors but particularly to the slow equilibrium between the concentration of the drug in the medium surrounding the slices and the biophase within the slices. Adenosine analogs bound specifically to membrane preparations of the rat hippocampus with the order of potency 3H-CHA greater than or equal to 3H-L-PIA greater than 3H-NECA. Eadie-Hofstee plots of the binding data were curvilinear for each ligand, but only for 3H-L-PIA could the existence of two binding sites with different apparent Kd-values (0.27 and 11.8 nM) be confirmed by curve-fitting. The estimated Kd-values for CHA and NECA were 1.5 and 20 nM, respectively. The adenosine analogs also enhanced 3H-cyclic AMP accumulation in 3H-adenine-labelled hippocampal slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1996

Mechanisms mediating insulin-induced hypotension in rats. A role for nitric oxide and autonomic mediators.

The mechanisms associated with insulin-induced cardiovascular inhibitory responses were evaluated in untreated normal rats and in normal rats pretreated with an antagonist of nitric oxide (NO) production (L-NAME), with cholinergic, alpha- and beta-adrenergic antagonists, or after ganglionic blockade. Male Wistar rats were anesthetized with a mixture of urethane and alpha-chloralose and placed on a electric heating pad. The femoral artery and vein were cannulated for measurements of mean arterial pressure (MAP), heart rate, plasma glucose, blood sampling, and intravenous injections. Intravenous injection of insulin (5.0 U/kg) in untreated rats resulted in a significant and sustained decrease in arterial blood pressure (average 24%) and in a slight decrease in heart rate. These cardiovascular responses were blocked by L-NAME and by the cholinergic antagonist atropine, suggesting an involvement of NO and the cholinergic receptors, or an effect of insulin on the central nervous system parasympathetic center. The ganglionic blocker hexamethonium attenuated the insulin-induced response. On the other hand, the hypotensive effect of insulin persisted after sympathetic blockade with the alpha-1 antagonist prazosin and the beta-1 antagonist atenolol. We conclude that the insulin-induced decrease in blood pressure is due to both increased cholinergic outflow and to NO production and that an enhanced sympathetic activity possibly mediated by a reactive release of norepinephrine or epinephrine modulates this response.

Animals↗
PubMed1980

[Follow-up study on antibody dependent cell-mediated cytotoxicity and cell-mediated cytotoxicity to HBs-antigen conjugated target cells in patients with hepatitis B (author's transl)].

Results of a follow up study on ADCC and CMC to HBs antigen conjugated target cells in patients with hepatitis B are given. The cytotoxic reaction was measured immediately after onset of the disease, three weeks and three months thereafter CMC was increased over the whole observation period. The results in hepatitis B patients were significantly different to those in normal controls. The ADCC in the presence of an antiserum to HBs antigen was in patients with hepatitis B immediately after onset of the disease reduced in comparison to the controls; it increased during the three months to the values of the controls in patients with uncomplicated disease. Experiments with isolated lymphocyte populations showed that the ADCC is mainly dependent on Fc receptor bearing lymphocytes whereas the CMC is mediated by T-cells and Fc-receptor bearing cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Separate purinoceptors mediate enhancement by adenosine of concanavalin A-induced mediator release and the cyclic AMP response in rat mast cells.

Adenosine caused a concentration-related enhancement of concanavalin A (Con A)-induced 5-hydroxytryptamine (5-HT) release from rat purified peritoneal mast cells. This was accompanied by an enhancement and prolongation of the cyclic AMP response to Con A. The cyclic AMP response but not enhancement of 5-HT release was blocked by 8-phenyltheophylline suggesting the two events to be unrelated. The effects of AMP and ADP, adenosine analogues and adenosine uptake inhibitors suggest the enhancement of 5-HT release to be mediated by a P1-cell surface purinoceptor which does not show the characteristics of either A1 or A2 subtypes.

Adenine Nucleotides↗
PubMed1998

H2 receptor-mediated facilitation and H3 receptor-mediated inhibition of noradrenaline release in the guinea-pig brain.

The effect of histamine and related drugs on the tritium overflow evoked electrically (0.3 Hz) or by introduction of Ca2+ ions into Ca2+-free K+-rich (25 mmol/l) medium containing tetrodotoxin was studied in superfused guinea-pig brain cortex, cerebellum, hippocampus or hypothalamus slices and in mouse brain cortex slices preincubated with 3H-noradrenaline. The electrically evoked tritium overflow in guinea-pig cortex slices was inhibited by histamine; the H3 receptor antagonist clobenpropit reversed the effect of histamine to a slight facilitation. The facilitatory effect of histamine (obtained in the presence of clobenpropit) was not affected by the H1 receptor antagonist mepyramine but abolished by the H2 receptor antagonist ranitidine. In the absence of clobenpropit, ranitidine augmented the inhibitory effect of histamine. In slices superfused in the presence of ranitidine, the evoked overflow was inhibited by histamine and, more potently, by the H3 receptor agonist R-alpha-methylhistamine in a concentration-dependent manner (maximum inhibitory effect obtained for both agonists 30-35%). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonist thioperamide. R-alpha-methylhistamine inhibited the electrically evoked tritium overflow also in guinea-pig cerebellar, hippocampal and hypothalamic slices. In cortex slices superfused in the presence of clobenpropit, the H2 receptor agonists impromidine and, less potently, R-sopromidine facilitated the evoked overflow in a concentration-dependent manner. S-Sopromidine only tended to increase the evoked overflow. The effect of impromidine was counteracted by the H2 receptor antagonists ranitidine and cimetidine. The extent of the maximum facilitatory effect of impromidine (by 15-20%) was about the same when (i) the Ca2+ concentration in the medium was reduced from 1.3 to 0.98 mmol/l, (ii) the time of exposure to impromidine was reduced from 28 to 8 min or (iii) cerebellar, hippocampal or hypothalamic slices were used instead of cortical slices. The Ca2+-induced tritium overflow in guinea-pig cortex slices was inhibited by histamine (in the presence of ranitidine); this effect was abolished by clobenpropit. In slices superfused in the presence of clobenpropit, impromidine failed to facilitate the Ca2+-evoked tritium overflow. The electrically evoked tritium overflow in mouse brain cortex slices was inhibited by histamine by about 60% (both in the absence or presence of ranitidine). The inhibitory effect of histamine was abolished (but not reversed) by clobenpropit. In conclusion, noradrenaline release in the guinea-pig brain cortex is inhibited via presynaptic H3 receptors and facilitated via H2 receptors not located presynaptically. In the mouse brain cortex, only inhibitory H3 receptors occur. The extent of the H3 receptor-mediated effect is more marked in the mouse than in the guinea-pig brain cortex.

Animals↗
PubMed2002

CGRP receptors in the gerbil spiral modiolar artery mediate a sustained vasodilation via a transient cAMP-mediated Ca2+-decrease.

Alteration of cochlear blood flow may be involved in the etiology of inner ear disorders like sudden hearing loss, fluctuating hearing loss and tinnitus. The aim of the present study was to localize the vasodilator calcitonin gene-related peptide (CGRP) and to identify CGRP receptors and their signaling pathways in the gerbil spiral modiolar artery (SMA) that provides the main blood supply of the cochlea. CGRP was localized in perivascular nerves by immunocytochemistry. The vascular diameter and cytosolic Ca2+ concentration [Ca2+]i in the smooth muscle cells were measured simultaneously with videomicroscopy and fluo-4-microfluorometry. Calcitonin receptor-like receptor (CRLR) mRNA was identified by RT-PCR as a specific 288 bp fragment in total RNA isolated from the vascular wall. The SMA was preconstricted by a 2-min application of 1 nM endothelin-1 (ET1). CGRP, forskolin, and dibutyryl-cAMP caused a vasodilation (EC50 = 0.1 nM, 0.3 mM, and 20 mM). CGRP and forskolin caused an increase in cAMP production and a transient decrease in the [Ca2+]i. The CGRP-induced vasodilation was antagonized by CGRP8-37 (KDB = 2 mM). The K+-channel blockers iberiotoxin and glibenclamide partially prevented the CGRP- or forskolin-induced vasodilations but failed to reverse these vasodilations. These results demonstrate that CGRP is present in perivascular nerves and causes a vasodilation of the ET1-preconstricted SMA. The data suggest that this vasodilation is mediated by an increase in the cytosolic cAMP concentration, a transient activation of iberiotoxin-sensitive BK and glibenclamide-sensitive KATP K+ channels, a transient decrease in the [Ca2+]i and a long-lasting Ca2+ desensitization.

Animals↗
PubMed1989

Activation of ACTH release is mediated by the same molecule as the final mediator, PGE2, of febrile response in rats.

Increase in the blood level of adrenocorticotropic hormone (ACTH) and fever are induced by i.v. administration of interleukin-1 alpha (IL-1 alpha) in rats. With preinjection of indomethacin, the ACTH and fever responses to i.v. IL-1 alpha were both either greatly reduced or abolished. Intrapreoptic microinjection of prostaglandin E2 (PGE2) caused ACTH and fever responses similar to those seen after i.v. IL-1 alpha. These data suggest that PGE2, a final mediator of fever, may be released by i.v. IL-1 alpha and also act centrally to enhance the release of corticotropic-releasing factor in the brain.

Adrenocorticotropic Hormone↗
PubMed1983

The mechanism of cell-mediated cytotoxicity. III. Protease-specific inhibitors preferentially block later events in cytotoxic T lymphocyte-mediated lysis than do inhibitors of methylation or thiol-reactive agents.

Highly active mouse cytotoxic T lymphocytes (CTL) generated in secondary mixed-lymphocyte responses were used to examine the manner in which adenosine derivatives, thiol-specific reagents, or protease-specific probes affected CTL-mediated lysis (CML). The adenosine deaminase inhibitor deoxycoformycin (dCF) enhanced inhibition by adenosine (AR) or by deoxyadenosine (AdR), but not by 7-deazaadenosine (tubercidin). L-Homocysteinethiolactone (L-Hcy) acted synergistically with AR, but not with AdR or tubercidin, to block CML. Thus, AR derivatives may act both by affecting cellular methylation reactions, as demonstrated by the synergism between AR and L-Hcy, and by inhibiting other events required for CML. Conditions were then established to determine whether these reagents preferentially affected either the Ca2+-independent initial stage of cytolysis or the subsequent Ca2+-dependent events. Methylation inhibitors blocked lysis most effectively if added before effector-target binding. Similarly, the nonpenetrating thiol-specific reagent quaternary ammonium monobromobimane (qBBr) was more inhibitory when added prior to the Ca2+-dependent stage. Protease inhibitors such as alpha-1-antichymotrypsin and protease substrates such as acetyltyrosine ethyl ester (ATEE) or tyrosine ethyl ester (TEE) also inhibited CML. But, in contrast to qBBr or methylation inhibitors, neither TEE nor ATEE was more effective when added prior to the initial effector-target interaction. Furthermore, TEE did not appreciably affect CTL binding to target cells at concentrations that nearly abrogated CML. Thus, the implicated protease step is unique in that it does not appear to participate in recognition or binding.

Adenosine↗
PubMed1983

Receptor-mediated particle uptake by liver macrophages. The galactose-particle receptor mediates uptake via coated and also non-coated structures.

The endocytosis pathways of particles with terminal beta-D-galactosyl groups were studied in isolated rat Kupffer cells by electron microscopy. Colloidal gold particles of sizes 5, 17 and 50 nm were coated with asialofetuin (ASF) and isolated liver macrophages were allowed to bind (at 4 degrees C) or take up (at 37 degrees C) these ligands. Particles of all three sizes were bound via the galactose-particle receptor as shown by carbohydrate inhibition experiments and were ingested effectively. But, whereas ASF-gold particles of sizes 5 and 17 nm are taken up via the coated pit/coated vesicle pathway, the 50 nm particles are not. These enter the cell via non-coated endocytic vacuoles. All three particle sizes are transported to the same lysosomal compartment. These observations demonstrate that at least in macrophages one receptor is capable to mediate endocytosis via two different pathways depending on ligand size and/or valency.

Animals↗
PubMed1992

The effect of epinephrine on glucose-mediated and insulin-mediated glucose disposal in insulin-dependent diabetes.

The aim of this study was to determine the relative roles of changes in glucose-mediated glucose disposal (SG) and insulin sensitivity (SI) on the impairment of glucose disposal caused by epinephrine (EPI) infusion in type I (insulin-dependent) diabetes mellitus (IDDM). Seven non-obese young adult diabetics with minimal endogenous insulin secretion had EPI infusions at 25 ng/kg/min for 5.5 hours, after a basal overnight insulin infusion (12 mU/kg/h), and glucose infusion as required to maintain euglycemia. The EPI infusion produced approximately an eightfold increase in plasma EPI. At 2.5 hours, an intravenous glucose tolerance test (IVGTT) was performed with supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. In random order, each subject also had a control (CTR) infusion of basal insulin before the IVGTT. The results were analyzed according to a modification of the minimal model of Bergman et al. EPI infusion was associated with (1) elevated basal plasma glucose (EPI v CTR, 9.8 +/- 0.3 SE v 7.7 +/- 0.7 mmol/L, P less than .05); (2) elevated plasma nonesterified fatty acids (NEFA, 0.9 +/- 0.1 v 0.3 +/- 0.1 mmol/L, P less than .05); and (3) profoundly reduced glucose disposal (KG 0.59 +/- 0.1 v 1.91 +/- 0.33 min-1 x 10(2), P less than .02). Further analysis showed that the reduced glucose disposal was attributable to a marked decrease in SI (EPI 0.9 +/- 0.5 v CTR 7.03 +/- 3.2 min-1.mU-1.L x 10(4), P less than .05) with no significant change in SG (EPI 2.5 +/- 0.2 v CTR 3.1 +/- 0.5 min-1 x 10(2), NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A long-lasting potentiation of calmodulin-mediated chloride channel activity without a mediation of protein kinase C in Xenopus oocytes injected with rat brain mRNA.

When Xenopus oocytes injected with rat brain poly(A)+RNA were voltage-clamped in a recording solution containing Ca2+, a depolarization pulse induced a transient current, ICl(Ca), which reflects calmodulin-mediated opening of endogenous Cl- channels in response to a Ca2+ influx through Ca2+ channels of brain origin. ICl(Ca) could be repetitively observed with a steady amplitude over 1 h, whereas the response was greatly potentiated for more than 30 min after a brief stimulation of muscarinic or other Ca2(+)-mobilizing receptors. The enhancement of ICl(Ca) was mimicked by an injection of inositol-1,4,5-trisphosphate or by a treatment with A23187, but not affected by treatments that stimulate or inhibit protein kinase C activity. Isolated Ba2+ current flowing through voltage-sensitive Ca2+ channels was not augmented during the facilitation of ICl(Ca). These observations indicate that the endogenous calmodulin/Cl- channel system may memorize an over-threshold increase in the intracellular Ca2+ concentration and potentiate the Ca2(+)-sensitiveness of the Cl- channel. A long-lasting autoregulation of Ca2(+)-dependent ion channel activity is suggested.

Acetylcholine↗
PubMed1994

CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model for CD14 mediated endogenous cytokine release in the treatment of AML.

In previous studies, HL60 AML cells treated with tumor necrosis factor-alpha (TNF), interferon-gamma (IFN), and lipopolysaccharides (LPS) displayed decreased growth and viability, enhanced monocytic pathway differentiation and endogenous TNF release. Endogenous TNF release by LPS/TNF/IFN treated HL60 cells was postulated to play a role with the above findings. In these studies, HL60 cells expressed CD14 when treated with TNF, IFN, and LPS. CD14 mediates TNF release in monocytes/macrophages in response to binding of LPS with LPS binding protein (LBP). CD14 was not expressed in either untreated or LPS only treated HL60 cells. CD14 expression was present and greater with HL60 cells cultured with LPS/TNF/IFN vs TNF/IFN (47.47% vs 9.07% positive, respectively) suggesting synergism for LPS in CD14 induction. CD14 expression was associated with endogenous TNF release, and with significantly higher levels by HL60 cells treated with LPS/TNF/IFN vs TNF/IFN (p < 0.001). Addition of anti-CD14 antibody significantly reduced release of TNF in TNF/IFN (p < 0.001) and LPS/TNF/IFN (p = 0.0013) treated cells. KG1 and U937 AML cells treated with LPS, TNF, and IFN did not express CD14, nor release TNF. A model for inducing release of endogenous growth inhibitory cytokines by CD14 bearing AML cells is proposed as an approach to AML therapy.

Antigens, CD↗
PubMed1994

Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro.

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1-4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8-11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP (D-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFN gamma mAb) was in culture. Whole SP and SP 8-11, but not SP 1-4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8-11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFN gamma).

Amino Acid Sequence↗
PubMed1996

HLA-A11-mediated protection from NK cell-mediated lysis: role of HLA-A11-presented peptides.

The capacity of MHC class I to protect target cells from NK is well established, but the mechanism by which these molecules influence NK recognition and the physical properties associated with this function remain poorly defined. We have examined this issue using as a model the HLA-A11 allele. HLA-A11 expression correlated with reduced susceptibility to NK and interferon-activated cytotoxicity in transfected sublines of the A11-defective Burkitt's lymphoma WW2-BL and the HLA class I A,B-null C1R cell line. Protection was also achieved by transfection of HLA-A11 in the peptide processing mutant T2 cells line (T2/A11), despite a very low expression of the transfected product at the cell surface. Induction of surface HLA-A11 by culture of T2/A11 cells at 26 degrees C or in the presence of beta 2m did not affect lysis, whereas NK sensitivity was restored by culture in the presence of HLA-All-binding synthetic peptides derived from viral or cellular proteins. Acid treatment rendered T2/A11 and C1R/A11 cells sensitive to lysis, but protection was restored after preincubation with peptide preparations derived from surface stripping of T2/A11 cells. Similar peptide preparations from T2 cells had no effect. The results suggest that NK protection is mediated by HLA-A11 molecules carrying a particular set of peptides that are translocated to the site of MHC class I assembly in the ER in a TAP-independent fashion.

Antigen Presentation↗
PubMed1994

Streptozotocin-induced diabetes selectively reduces antinociception mediated by mu 1-opioid receptors, but not that mediated by mu 2-opioid receptors.

We assessed the effect of naloxonazine, a selective mu 1-opioid receptor antagonist, on antinociception produced by intrathecal or intracerebroventricular injections of morphine in streptozotocin-induced diabetic mice. The antinociceptive effect of morphine (10 micrograms), administered i.c.v., was significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. morphine was significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine. There were no significant differences in the antinociceptive effect of morphine (1 microgram, i.t.) in diabetic and non-diabetic mice. Furthermore, naloxonazine had no significant effect on the antinociceptive effect of i.t. morphine in either diabetic or non-diabetic mice. On the other hand, the antinociceptive effects of i.c.v. and i.t. morphine were significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. In conclusion, mice with diabetes are selectively hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception, but are normally responsive to activation of spinal mu 2-opioid receptors.

Analgesics↗
PubMed1986

Development of specific antibodies mediating antibody-dependent cell-mediated cytotoxicity following experimental infection of cattle with bovine herpesvirus 1 and subsequent viral reactivation.

Evolution of sensitizing antibodies involved in antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-complement cell lysis and complement-facilitated ADCC was followed in bulls after primary infection by a wild strain of infectious bovine rhinotracheitis virus (bovine herpesvirus 1; BHV-1) and after experimental reactivation of the virus. These antibodies were detected between the 4th and the 7th day after primary infection, reached a maximum level after 2 weeks and rose slightly after reactivation of the virus following dexamethasone treatment. The presence of endogenous complement slightly enhanced the ADCC reaction.

Animals↗
PubMed1990

Failure of nitroglycerin and diltiazem to reduce platelet-mediated vasoconstriction in dogs with coronary artery stenosis and endothelial injury: further evidence for thromboxane A2 and serotonin as mediators of coronary artery vasoconstriction in vivo.

This study was designed to test the efficacy of nitroglycerin and diltiazem in inhibiting in vivo platelet aggregation and reducing platelet-mediated vasoconstriction in a canine model of coronary artery stenosis and endothelial injury. Coronary artery diameter was measured in vivo by means of ultrasonic crystals sutured on the left anterior descending coronary artery (LAD) immediately distal to an external constrictor (LAD1), 1 cm below (LAD2), and on the left circumflex coronary artery. Coronary diameter was continuously measured before, during cyclic flow variations (progressive declines in blood flow followed by sudden restorations of flow due to recurrent intracoronary platelet aggregation), during cyclic flow variations and intravenous infusion of nitroglycerin (5 micrograms/kg per min) or diltiazem (15 micrograms/kg per min), and after cyclic flow variations were abolished by administration of LY53857, a serotonin receptor antagonist (n = 7), or SQ29548, a thromboxane A2 receptor antagonist (n = 7). During control cyclic flow variations, at the nadir of coronary flow (6% to 11% of the nonstenosed values), LAD1 cross-sectional area decreased by 43 +/- 8% and 44 +/- 3% in the two groups of dogs subsequently treated with LY53857 and SQ29548, respectively. Neither nitroglycerin nor diltiazem caused changes in cyclic flow variation frequency or severity. Furthermore, neither drug significantly reduced the vasoconstriction associated with cyclic flow variations, whereas they significantly increased circumflex artery cross-sectional area. In contrast, LY53857 and SQ29548 were very effective in abolishing cyclic flow variations and the coronary vasoconstriction related to them. Five additional dogs received an intracoronary infusion of nitroglycerin (21 +/- 5 micrograms/kg per min) and later diltiazem (15 micrograms/kg per min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Arterial compliance influences the measurement of flow-mediated vasodilation, but not acetylcholine-mediated forearm blood flow. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

OBJECTIVES: Flow-mediated vasodilation (FMD) is low even in healthy elderly and therefore relations between FMD and cardiovascular risk factors might be hard to evaluate in the elderly. Using data from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we investigated if a reduced arterial distensibility could influence FMD measurements. METHODS: In the population-based PIVUS study (1016 subjects aged 70), assessments of arterial distensibility by ultrasound in the carotid artery (CCA) and FMD were performed. Endothelium-dependent vasodilation was also evaluated with the invasive forearm technique with acetylcholine (EDV) and by pulse wave analysis following terbutaline injection. A poor CCA distensibility was defined as <25th percentile in the healthy part of the population (n=131). RESULTS: FMD was significantly related to the Framingham risk score only in those with a good CCA distensibility (r=-0.16, p=0.0081 versus r=-0.06, p=0.17 in those with a poor CCA distensibility, p=0.0001 for difference). In contrast, the relationship between EDV and coronary risk was not affected by CCA distensibility (r=-0.11, p=0.018 versus r=-0.13, p=0.027). CONCLUSIONS: A reduced CCA distensibility could in part explain the low FMD values in the elderly. FMD correlated to the Framingham risk score only in those with a good CCA distensibility, exemplifying a limitation of the use of FMD in elderly populations. On the contrary, EDV was not affected by arterial stiffness.

Acetylcholine↗