Browsing by Author "Gök, S"

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    Effect of vitamin E on vascular responses of thoracic aorta in rat experimental arthritis
    Çinar, MG; Can, C; Ülker, S; Gök, S; Çoker, C; Soykan, N; Kosay, S; Evinç, A
    1. Vascular contractile and relaxant responses were evaluated in isolated aortic rings of adjuvant induced arthritic rats in comparison with control rats, and the effect of an antioxidant treatment on the development of the arthritis was investigated by vitamin E administration (100 mg/kg/day, IM, for 26 days). 2. Arthritis was induced by an intradermal injection of Freund's complete adjuvant into rat paw. Vascular responses, arthritic lesions and serum copper levels were evaluated after 26 days from adjuvant inoculation. 3. Serum copper levels were significantly lower in arthritic rats than in the control. 4. The contractile response of aortic rings to phenylephrine (PE), but not to KCl, was increased in preparations from arthritic rats, which could be explained by an enhancement of intracellular calcium contents. 5. Acetylcholine (Ach)-mediated endothelium-dependent and sodium nitroprusside (SNP)-mediated endothelium-independent relaxations were not changed significantly in vascular preparations from arthritic rats. 6. In arthritic rats, vitamin E treatment improved arthritic lesions with an increase in copper levels. Despite this ameliorating effect, vitamin E treatment caused an increase in contractile response to PE and a decrease in the relaxant response to Ach and SNP in arthritic rats. 7. These data show that vitamin E provides ameliorating effects in improving systemic signs of experimental arthritis, but it fails to restore abnormalities in vascular function, indicating that adjuvant-induced alterations in vascular function may include mechanisms other than oxygen-free radical formation. (C) 1998 Elsevier Science Inc.
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    Possible contribution of leukotrienes in the arrhythmogenic effects of digoxin on isolated guinea-pig hearts
    Gök, S; Ülker, S; Evinç, A
    The effect of a leukotriene D-4 (LTD4) receptor antagonist, L-648,051, was investigated in digoxin-induced cardiac toxicity in isolated guinea-pig hearts (Langendorff preparation). Digoxin infusion (25 mu g.ml(-1), 0.5 ml.min(-1)) increased perfusion pressure and contractile force initially, but decreased them later. The onset of first ventricular premature beats (VPBs) matched the increase phase, but the decrease phase was accompanied by ventricular tachycardia (VT) and fibrillation (VF). In the presence of L-648,051 (5 mu mol.l(-1)), the initial phase was similar to that observed with digoxin alone, but the marked reduction was inhibited. This drug increased the concentration of digoxin required for VBSs and cardiac arrest, but it could not prevent the formation of VT and VF. The duration of VT was significantly decreased by L648,051. It is concluded that the leukotriene receptor antagonist might have beneficial effects on digoxin-induced arrhythmias. Whether this effect depends on direct or indirect actions is uncertain.
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    Glutamate mGlu5 receptor antagonist, MPEP, reduces the quinpirole-induced compulsive-like checking in rats
    Gök, S; Demet, MM; Öztürk, Z
    There is increasing evidence for an interaction between dopaminergic and glutamatergic systems in obsessive compulsive disorder (OCD). In the present study, it was tested whether group I metabotropic glutamate 5 receptors (mGlu5R) mediate compulsive-like checking behavior in an animal OCD model induced by quinpirole, a dopamine D2/3 receptor agonist. Rats were tested on a large open field with four boxes placed in different locations. To induce locomotor sensitization, rats were administered quinpirole chronically (0,5 mg kg(-1), twice a week for 5 weeks, sc). In the treated group, 2-methyl-6-(phenyl ethynyl) pyridine (MPEP), an mGluR5 antagonist was administered to rats (1 or 5 mg kg(-1), i.p.) prior to each quinpirole injection. The distance traveled and the speed of rats were used to assess locomotor activity. After each rat's checking place was identified, the number of visits and the length of check were used as the main criteria to assess the compulsive checking behavior. The results showed that treatment of MPEP significantly inhibited the increase in QNP-induced increase in locomotion and compulsive control behavior. Our findings, therefore, support the hypothesis that mGluR5 receptors mediate dopaminergic compulsive-like control behavior.
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    Role of leukotrienes on coronary vasoconstriction in isolated hearts of arthritic rats
    Gök, S; Ülker, S; Hüseyinov, A; Hatip, FB; Çinar, MG; Evinç, A
    In this study, coronary perfusion pressure and force of contraction were investigated in isolated hearts removed from arthritic rats by using the Langendorff method. A strong coronary vasoconstriction was determined in arthritic hearts which was associated with elevated levels of arachidonate 5-lipoxygenase (5-LOX) products, leukotriene B-4 (LTB4) and LTC4 in coronary effluents. In vivo treatment with the dual inhibitor of cyclooxygenase (COX) and LOX, CI-986 (2 and 10 mg/kg/day) on days 14-26 following adjuvant injection, prevented the coronary vasoconstriction and the increased production of LTB4 and LTC4. These results suggest that the coronary vasoconstriction in the isolated arthritic hearts is associated with an increased activity of the LOX system and CI-986 could have a preventive effect on constriction of coronary arteries. Copyright (C) 2000 S. Karger AG, Basel.
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    The antinociceptive effect of leukotriene D4 receptor antagonist, MK-571, in mice
    Gök, S; Önal, A; Çinar, MG; Evinç, A
    The effect of a leukotriene D-4 receptor antagonist, (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl) amino-3-oxo plopyl)thio)methyl)thio) propanoic acid (L-660,711; MK-571), was investigated on nociceptive responses in mice using three different assays: acetic-acid-induced abdominal constrictions, formalin response and tail-flick test. MK-571 (8-32 mg/kg, i.v.) produced dose-dependent protection against acetic-acid-induced abdominal constriction (ED50 = 30 mg/kg). The compound (10-80 mg/kg, i.p.) was also effective, in a dose-dependent manner, on the second phase of the formalin response (ED50 = 26 mg/kg). However, it had no effect on the first phase of the formalin response and in the tail-flick test. Naloxone (1 mg/kg, i.v.), an opioid antagonist, almost completely blocked the antinociceptive effect of MK-571 in both acetic-acid-induced abdominal constriction and the second phase of the formalin test. These results provide evidence for an antinociceptive action of MK-571 at peripheral sites and suggest that opioid mechanisms are involved. (C) 1999 Elsevier Science B.V. All rights reserved.