European Journal of Pharmacology (v.484, #1)
Editorial Board (ii).
Inhibitory effect of trilinolein on angiotensin II-induced cardiomyocyte hypertrophy by Ju-Chi Liu; Tzu-Hurng Cheng; Horng-Mo Lee; Wen-Sen Lee; Neng-Lang Shih; Yen-Ling Chen; Jin-Jer Chen; Paul Chan (1-8).
The myocardial protective effects of trilinolein, isolated from the Chinese herb Sanchi (Panax notoginseng), may be related to its antioxidant effects. In the present study, we investigated the effects of trilinolein on angiotensin II-induced cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were stimulated with angiotensin II, [3H]leucine incorporation and the β-myosin heavy chain promoter activity were examined. We also examined the effects of trilinolein on angiotensin II-induced intracellular reactive oxygen species generation. Trilinolein significantly inhibited angiotensin II-increased protein synthesis, β-myosin heavy chain promoter activity, and intracellular reactive oxygen species generation. Antioxidant N-acetylcysteine also decreased angiotensin II-increased protein synthesis and β-myosin heavy chain promoter activity. Furthermore, trilinolein and N-acetylcysteine decreased angiotensin II- or hydrogen peroxide (H2O2)-activated mitogen-activated protein kinases (MAPKs) phosphorylation, and activator protein-1 (AP-1)- [or nuclear factor-κB (NF-κB)]-reporter activities. These data indicate that trilinolein inhibits angiotensin II-induced cardiomyocyte hypertrophy and β-myosin heavy chain promoter activity via attenuation of reactive oxygen species generation.
Keywords: Angiotensin II; Trilinolein; Cardiomyocyte hypertrophy; Reactive oxygen species; MAP (mitogen-activated protein) kinase; β-myosin heavy chain;
Inhibition of arachidonic acid release and cytosolic phospholipase A2α activity by d-erythro-sphingosine by Hiroyuki Nakamura; Testuya Hirabayashi; Akiyoshi Someya; Masaya Shimizu; Toshihiko Murayama (9-17).
Sphingolipid metabolites such as sphingosine 1-phosphate (S1P) and ceramide can mediate many cellular events including apoptosis, stress responses and growth arrest. Although ceramide stimulates arachidonic acid metabolism in several cells, the effects of sphingosine and its endogenous analogs have not been established. We investigated the effects of d-erythro-sphingosine and its metabolites on arachidonic acid release in the two cells and on the activity of cytosolic phospholipase A2α. C2-Ceramide (N-acetyl-d-erythro-sphingosine, 100 μM) alone stimulated [3H]arachidonic acid release and enhanced the ionomycin-induced release from the prelabeled PC12 cells and L929 cells. In contrast, exogenous addition of d-erythro-sphingosine inhibited the responses in a concentration-dependent manner in the two cell lines. d-erythro-sphingosine, d-erythro-N,N-dimethylsphingosine (d-erythro-DMS) and d-erythro-dihydrosphingosine (d-erythro-DHS) significantly inhibited mastoparan-, but not Na3VO4-, stimulated arachidonic acid release in PC12 cells. d-erythro-S1P and dl-threo-DHS showed no effect on the responses. Production of prostaglandin F2α was also enhanced by C2-ceramide (20 μM) and suppressed by d-erythro-sphingosine (10 μM) in PC12 cells. An in vitro study revealed that d-erythro-sphingosine, d-erythro-DMS and d-erythro-DHS directly inhibited cytosolic phospholipase A2α activity. These findings suggest that ceramide and d-erythro-analogs of sphingosine have opposite effects on phospholipase A2 activity and thus regulate arachidonic acid release from cells.
Keywords: d-erythro-sphingosine; d-erythro-dihydrosphingosine; d-erythro-N,N-dimethylsphingosine; Arachidonic acid; Phospholipase A2; PC12 cell;
Influence of glucose concentration on the effects of aspirin, ticlopidine and clopidogrel on platelet function and platelet–subendothelium interaction by José Pedro De La Cruz; Marı́a Monsalud Arrebola; Marı́a Auxiliadora Villalobos; Araceli Pinacho; Ana Guerrero; José Antonio González-Correa; Felipe Sánchez de la Cuesta (19-27).
Clinical studies have shown that the ability of aspirin to prevent cerebrovascular accidents is weaker in patients with diabetes. The aim of this study was to determine whether high concentrations of glucose modified the effect of aspirin, ticlopidine and clopigodrel on platelet function and platelet–subendothelium interactions. This in vitro study tested three different concentrations of glucose. The effects were analyzed by comparing platelet aggregometry in whole blood, nitric oxide and prostacyclin production in cultures of human endothelial cells, and by quantitative analysis of morphological features of the platelet–subendothelium interaction under flow conditions. High concentrations of glucose increased platelet aggregation (13.9 Ω with 5 mM glucose vs. 21.6 Ω with 16.6 mM) and platelet–subendothelium interactions (28.9% with 5 mM glucose vs.35.2% with 16.6 mM), and decreased nitric oxide and prostacyclin production. In the presence of high concentrations of glucose, the antiaggregant effect of aspirin and its influence on nitric oxide production were diminished (IC50 54 μM with 5 mM glucose vs.556 μM with 16.6 mM glucose), and its effect on the platelet–subendothelium interaction was reduced (10.5% platelet occupancy with 5 mM glucose vs.23% with 16.6 mM glucose). The effects of ticlopidine and clopidogrel were not significantly modified.
Keywords: Aspirin; Ticlopidine; Clopidogrel; Platelet; Nitric oxide (NO); Platelet–subendothelium interaction.;
Celecoxib simulates respiratory burst through pertussis toxin-sensitive G-protein, a possible signal for β2-integrin expression on human neutrophils by Liao Chang-Hui; Hsiech Yen-Ju; Lin Yin-Chou (29-39).
The superoxide anion-generating effect of celecoxib (4-[5-(4-methylpheny)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide); SC58633), a selective cyclooxygenase-2 inhibitor, on human neutrophils was evaluated in this study. Celecoxib induced superoxide anion generation in a concentration-dependent manner in human neutrophils. The EC50 value of celecoxib on superoxide anion generation was 15.5±2.5 μM. A NADPH oxidase inhibitor, diphenyliodonium (20 μM), and superoxide dismutase (150 U/ml) completely inhibited the free radical generation caused by celecoxib, indicating that the respiratory burst was activated by celecoxib. 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM;10 μM) and staurosporine (200 nM) completely inhibited the superoxide anion release caused by celecoxib, respectively. These data indicated that celecoxib increased superoxide anion release by increasing intracellular calcium and protein kinase C activation. Moreover, 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-C)-carbazole (Go-6976; 1 μM) and 3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)maleimide, methane sulfate (Ro-31-8220; 0.5 μM), specific inhibitors of conventional protein kinase C isotypes (α, βI and βII), significantly inhibited superoxide anion release caused by celecoxib. Rottlerin (5 μM), a protein kinase C δ inhibitor, did not affect the free radical generation caused by celecoxib. Celecoxib caused translocation of protein kinase C α, βI and βII from the cytosol to the cellular membrane. 2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one (PD98059; 20 μM) and wortmannin (100 nM) did not decrease the superoxide anion generation caused by celecoxib, indicating that Mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3 kinase) were not involved in the respiratory burst induced by celecoxib. Pertussis toxin (2 μg/ml), a Gi-protein sensitive inhibitor, significantly inhibited superoxide anion release. Moreover, pertussis toxin significantly inhibited intracellular calcium mobilization and protein kinase C α, βI and βII translocation from the cytosol to the membrane. Celecoxib increased β2-integrin expression on human neutrophils and this effect was inhibited by BAPTA/AM (10 μM), superoxide dismutase (150 U/ml), genistein (25 μM) and PD98059 (20 μM). This information indicated that intracellular calcium, superoxide anion, tyrosine kinase and MAP kinase are involved in β2-integrin expression. Furthermore, BAPTA/AM, superoxide dismutase and genistein inhibited celecoxib-increased MAP kinase activity, indicating that MAP kinase is a downstream signal for β2-integrin expression. In conclusion, celecoxib stimulates superoxide anion release from human neutrophils by activating pertussis toxin sensitive G-protein. An increase in intracellular calcium and protein kinase C α, βI and βII is involved in this process. Celecoxib also regulates β2-integrin expression through superoxide anion release, tyrosine kinase and p42/p44 MAP kinase on human neutrophils.
Keywords: Celecoxib; Cyclooxygenase-2; Superoxide anion; Respiratory burst; Neutrophil; Protein kinase C (PKC); Ca2+ intracellular; Genistein;
Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells by Martin Traebert; Bérengère Dumotier; Lothar Meister; Peter Hoffmann; Manuel Dominguez-Estevez; Willi Suter (41-48).
Several antimalarial drugs are known to produce a QT interval prolongation via a blockade of the rapidly activating delayed rectifier K+ current (I Kr), encoded by the human-ether-a-go-go-related gene (hERG). We investigated the influence of lumefantrine and its major metabolite desbutyl-lumefantrine, as well as halofantrine, chloroquine, and mefloquine, on wild type hERG K+ channels in stably transfected human embryonic kidney cells (HEK293) using the whole cell patch-clamp technique. All of the tested antimalarial drugs inhibited the hERG K+ channels in a concentration- and time-dependent manner. Only halofantrine blocked hERG tail currents voltage-dependently. The ranking of the half-maximal inhibitory concentrations (IC50) of the antimalarials was: halofantrine (0.04 μM)<chloroquine (2.5 μM)<mefloquine (2.6 μM)<desbutyl-lumefantrine (5.5 μM)<lumefantrine (8.1 μM). Lumefantrine and desbutyl-lumefantrine showed a slower inhibition of I Kr than the other tested antimalarials. In conclusion, lumefantrine and desbutyl-lumefantrine inhibited significantly the hERG tail current with a higher IC50-value than mefloquine, chloroquine and halofantrine. This, together with the calculated cardiac safety indices, suggests that lumefantrine and desbutyl-lumefantrine have a weaker proarrhythmic potential than their comparator compounds.
Keywords: hERG K+ channel; Electrophysiology; Antimalarial drug; IC50;
Influence of carbenoxolone on the anticonvulsant efficacy of conventional antiepileptic drugs against audiogenic seizures in DBA/2 mice by Pietro Gareri; Daniele Condorelli; Natale Belluardo; Santo Gratteri; Guido Ferreri; Eugenio Donato Di Paola; Angela De Sarro; Giovambattista De Sarro (49-56).
Carbenoxolone, the succinyl ester of glycyrrhetinic acid, is an inhibitor of 11β-hydroxy steroid dehydrogenase and gap junctional intercellular communication. It is currently used in clinical treatment of ulcer diseases. Systemic administration of carbenoxolone (1–40 mg/kg, intraperitoneally (i.p.)) was able to produce a dose-dependent decrease in DBA/2 audiogenic seizure severity score. Glycyrrhizin, an analogue of carbenoxolone inactive at the gap-junction level, was unable to affect audiogenic seizures at doses up to 30 mg/kg. In combination with conventional antiepileptic drugs, carbenoxolone, 0.5 mg/kg, i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. This effect was not observed after the combination of glycyrrhizin (10 mg/kg, i.p.) with some conventional antiepileptic drugs. The degree of potentiation induced by carbenoxolone was greater for diazepam, felbamate, gabapentin, phenobarbital and valproate, less for lamotrigine, phenytoin and carbamazepine. This increase was associated with a comparable impairment in motor activity; however, the therapeutic index of combined treatment of antiepileptic drugs with carbenoxolone was more favourable than the combination with glycyrrhizin or saline. Since carbenoxolone did not significantly influence the total and free plasma levels of diazepam, felbamate, gabapentin, lamotrigine, phenytoin, phenobarbital, valproate and carbamazepine, pharmacokinetic interactions are not likely. However, the possibility that carbenoxolone can modify the brain clearance of the anticonvulsant drugs studied may not be excluded. In addition, carbenoxolone did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, carbenoxolone showed an additive anticonvulsant effect when administered in combination with some classical anticonvulsants, most notably diazepam, felbamate, gabapentin, phenobarbital, and valproate, implicating a possible therapeutic relevance of such drug combinations.
Keywords: Epilepsy; Carbenoxolone; Gap junction; Antiepileptic drug; Carbamazepine; Phenytoin; Valproate; Felbamate; Anticonvulsant potency; Audiogenic seizure; DBA/2;
Stress-induced increase of cortical dopamine metabolism: attenuation by a tachykinin NK1 receptor antagonist by Peter H. Hutson; Shil Patel; Mark T. Jay; Cheryl L. Barton (57-64).
The present study examined the potential role of tachykinin NK1 receptors in modulating immobilisation stress-induced increase of dopamine metabolism in rat medial prefrontal cortex. In agreement with previous studies, 20 min immobilisation stress significantly increased medial prefrontal cortex dopamine metabolism as reflected by the concentration of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC). Pretreatment with the high affinity, selective, tachykinin NK1 receptor antagonist (3(S)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethyl amino)-2(S)-phenylpiperidine) ((S)-GR205171, 10 mg/kg, s.c.), a dose that in ex vivo binding studies extensively occupied rat brain tachykinin NK1 receptors for approximately 60 min, significantly attenuated the stress-induced increase of mesocortical DOPAC concentration without affecting cortical DOPAC levels per se. In contrast, pretreatment of animals with the less active enantiomer (R)-GR205171 (10 mg/kg, s.c.), which demonstrated negligible tachykinin NK1 receptor occupancy ex vivo, failed to affect either basal or stress-induced DOPAC concentration in medial prefrontal cortex. Furthermore, pretreatment of animals with the benzodiazepine/GABAA receptor antagonist, flumazenil (15 mg/kg, i.p.), did not affect the ability of (S)-GR205171 to attenuate the increase of medial prefrontal cortex DOPAC concentration by acute stress. Results demonstrate that the selective tachykinin NK1 receptor antagonist, (S)-GR205171, attenuated the stress-induced activation of mesocortical dopamine neurones by a mechanism independent of the benzodiazepine modulatory site of the GABAA receptor.
Keywords: Tachykinin NK1 receptor antagonist; GR205171; Immobilisation stress; Cortex; Dopamine metabolism; Tachykinin NK1 receptor occupancy; [125I]Tyrosine–substance P ex vivo binding;
Treatment with tamoxifen reduces hypoxic–ischemic brain injury in neonatal rats by Yangzheng Feng; Jonathan D. Fratkins; Michael H. LeBlanc (65-74).
Tamoxifen, an estrogen receptor modulator, is neuroprotective in adult rats. Does tamoxifen reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of hypoxia (8% oxygen). Tamoxifen (10 mg/kg) or vehicle was given i.p. 5 min prior to hypoxia, or 5 min after reoxygenation, with a second dose given 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere 22 days following hypoxia and gross and microscopic morphology. Tamoxifen pre-treatment reduced brain weight loss from 21.5±4.0% in vehicle pups (n=27) to 2.6±2.5% in the treated pups (n=22, P<0.05). Treatment 5 min after reoxygenation reduced brain weight loss from 27.5±4.0% in vehicle pups (n=42) to 12.0±3.9% in the treated pups (n=30, P<0.05). Tamoxifen reduces brain injury in the neonatal rat.
Keywords: Tamoxifen; Neuroprotection; Oxygen radical; Thiobarbituric acid reactive substance; Rat;
Decreased postsynaptic dopaminergic and cholinergic functions in the ventrolateral striatum of spontaneously hypertensive rat by Satoshi Fujita; Kazunori Adachi; Jun Lee; Takuya Uchida; Noriaki Koshikawa; Alexander R. Cools (75-82).
Dopamine and acetylcholine receptor functions in spontaneously hypertensive rats (SHR) and in control progenitor Wistar–Kyoto (WKY) rats were assessed, using dopamine D1-like/D2-like receptor-mediated and acetylcholine receptor-mediated jaw movements as readout parameters. Spontaneous behaviours such as locomotor activity, vacuous chewing, grooming, sniffing and rearing occurred significantly more in SHR than in WKY rats. In the anaesthetised rats, a mixture of SKF 38393 (5 μg), a dopamine D1-like receptor agonist, and quinpirole (10 μg), a dopamine D2-like receptor agonist, readily produced repetitive jaw movements in WKY rats, but not SHR, when bilaterally injected into the ventrolateral striatum; such injections into the nucleus accumbens shell were ineffective in each strain. Bilateral injections of carbachol (2.5 μg each side), an acetylcholine receptor agonist, into the ventrolateral striatum elicited repetitive jaw movements in both SHR and WKY rats, but to a far less degree in SHR. The present study demonstrates that spontaneous behaviours are enhanced in SHR, and that postsynaptic dopamine D1-like/D2-like receptors and acetylcholine receptors in the ventrolateral striatum of SHR are hyposensitive when compared to those of WKY rats.
Keywords: Attention-deficit hyperactivity disorder; Spontaneous behaviour; Repetitive jaw movement; Striatum; Ventrolateral; Dopamine D1-like/D2-like receptor; Acetylcholine receptor; Spontaneously hypertensive rat (SHR);
Activation of histamine H3 receptors in human nasal mucosa inhibits sympathetic vasoconstriction by LoriAnn M Varty; Eric Gustafson; Maureen Laverty; John A Hey (83-89).
The peripheral histamine H3 receptor is a presynaptic heterologous receptor located on postganglionic sympathetic nerve fibers innervating sympathetic effector systems such as blood vessels and the heart. An extensive body of evidence shows that activation of the histamine H3 receptor attenuates sympathetic tone by presynaptic inhibition of noradrenaline release. It is proposed that this sympathoinhibitory action, in vivo, leads to reduced vasoconstriction, thereby eliciting a vasodilatory effect.In humans, the peripheral histamine H3 receptor has also been shown to exert a sympathoinhibitory function on specific peripheral autonomic effector systems. For example, human saphenous vein and heart possess functional presynaptic histamine H3 receptors on the sympathetic nerve terminals that upon activation decrease the sympathetic tone to these respective organs. The present studies were conducted to define the role of histamine H3 receptors on neurogenic sympathetic vasoconstrictor responses in human nasal turbinate mucosa. Contractility studies were conducted to evaluate the effect of histamine H3 receptor activation on sympathetic vasoconstriction in surgically isolated human nasal turbinate mucosa. We found that the histamine H3 receptor agonist, (R)-α-methylhistamine (30 and 300 nM), inhibited electrical field stimulation-induced (neurogenic) sympathetic vasoconstriction in a concentration-dependent fashion. Pretreatment with the selective histamine H3 receptor antagonist, clobenpropit (100 nM), blocked the sympathoinhibitory effect of (R)-α-methylhistamine on the neurogenic sympathetic vasoconstriction. In addition, analysis of Taqman mRNA expression studies showed a specific, high level of distribution of the histamine H3 receptor localized in the human nasal mucosa.Taken together, these studies indicate that histamine H3 receptors modulate vascular contractile responses in human nasal mucosa most likely by inhibiting noradrenaline release from sympathetic nerve terminals in nasal mucosa. It is further suggested that histamine H3 receptors may play a role in the regulation of vascular tone and nasal patency in histamine-dependent allergic nasal congestive disease.
Keywords: Histamine H3 receptor; Nasal mucosa; Sympathetic; Taqman;
Homologous desensitization of calcitonin gene-related peptide-induced relaxation in rat intramural coronary arteries by Majid Sheykhzade; Niels C Berg Nyborg (91-101).
We investigated the type of desensitization of calcitonin gene-related peptide (CGRP)-induced responses in rat isolated intramural coronary arteries using isometric myograph and FURA-2 technique. In coronary arteries precontracted with 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α (U46619), development of tachyphylaxis to CGRP is characterized by significant attenuation of CGRP-induced maximal reduction in the tension and [Ca2+]i during the second CGRP concentration–response curve; however, there was no further reduction in the CGRP-induced maximum relaxation during the third CGRP concentration–response curve. There was no sign of tachyphylaxis to CGRP when CGRP concentration–response curves were recorded in 36 mM K+-depolarized coronary arteries contrary to the results obtained in 300 nM U46619-precontracted coronary arteries. Preincubation with colchicine did not prevent the development of tachyphylaxis to CGRP in U46619-precontracted coronary arteries, indicating no role for endocytosis. Development of tachyphylaxis to CGRP was completely abolished by preincubating the coronary arteries with 1 μM RO 31-8220, indicating a role for protein kinases. Pre-exposure of the coronary arteries to isoprenaline or forskolin did not attenuate the CGRP-induced relaxation in these vessels, indicating that the cAMP–protein kinase A (PKA) pathway is not involved. Like CGRP, the coronary arteries developed tachyphylaxis toward isoprenaline during the second exposure. However, there was no sign of tachyphylaxis to either forskolin or dibutyryl cAMP (dbcAMP) during the second exposure. In conclusion, these results suggest that development of tachyphylaxis to CGRP in U46619-precontracted coronary is related to CGRP receptor-mediated activation of protein kinase.
Keywords: Desensitization; CGRP (calcitonin gene-related peptide); Coronary artery;
Ischemic heart disease induce upregulation of endothelin receptor mRNA in human coronary arteries by Angelica Wackenfors; Malin Emilson; Richard Ingemansson; Tibor Hortobagyi; Delia Szok; Janos Tajti; Laszlo Vecsei; Lars Edvinsson; Malin Malmsjö (103-109).
Endothelin has been implicated in the pathogenesis of ischemic heart disease and congestive heart failure. The aims were to quantify endothelin type A (ETA) and type B (ETB) receptor mRNA levels in human coronary arteries from patients with ischemic heart disease, congestive heart failure and controls using real-time polymerase chain reaction (real-time PCR). In addition, the suitability of organ culture as a model mimicking endothelin receptor changes in cardiovascular disease was evaluated by in vitro pharmacology and real-time PCR. Endothelin ETA and ETB receptor mRNA levels were significantly higher in arteries from patients with ischemic heart disease (0.23±0.04 and 0.35±0.06) as compared to congestive heart failure (0.09±0.02 and 0.07±0.01) and controls (0.08±0.02 and 0.08±0.01). After organ culture, the endothelin ETB receptor mRNA levels were elevated, and the sarafotoxin 6c-induced vasoconstriction was more efficacious. Increased endothelin receptor activity may contribute to the increased vascular tone and development of atherosclerotic disease in ischemic heart disease in man.
Keywords: Cardiovascular disease; Coronary artery; Endothelin; Gene expression; Endothelin receptor; Vasoconstriction;
Superoxide dismutase entrapped-liposomes restore the impaired endothelium-dependent relaxation of resistance arteries in experimental diabetes by Manuela Voinea; Adriana Georgescu; Adrian Manea; Elena Dragomir; Ileana Manduteanu; Doina Popov; Maya Simionescu (111-118).
Diabetes is associated with impaired endothelium-dependent relaxation. We questioned whether administration of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 18.104.22.168) entrapped in long-circulating liposomes improves the vascular reactivity of the resistance arteries. Using the myograph technique, the vasodilation in response to acetylcholine was measured in mesenteric resistance arteries isolated from diabetic or normal hamsters treated for 3 days with superoxide dismutase entrapped in liposomes, with the same concentrations of free superoxide dismutase and plain liposomes, or untreated. Superoxide dismutase activity and nitric oxide (NO) levels were assayed by spectrophotometry, superoxide dismutase levels by Western blot and the role of N ϖ-nitro-l-arginine ethylester (l-NAME) on vasodilation by the myograph technique. Our data revealed that: (i) superoxide dismutase entrapped in liposomes restored to a great extent the endothelium-dependent relaxation of diabetic hamster resistance arteries; (ii) in superoxide dismutase entrapped in liposomes-treated diabetic animals, the activity and the level of superoxide dismutase in arterial homogenates as well as the serum nitrite levels were significantly higher than those in untreated hamsters or hamsters treated with free superoxide dismutase and plain liposomes: (iii) l-NAME inhibited the response of arteries to acetylcholine in superoxide dismutase entrapped in liposomes-treated diabetic hamsters. These results suggest that superoxide dismutase entrapped in liposomes is effective in scavenging superoxide anions, increases nitric oxide bioactivity and improves the vasorelaxation of resistance arteries in diabetic hamsters.
Keywords: Artery; Diabetes; Liposome; Superoxide dismutase; Vasodilation;