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Öğe 5-Hydroxytryptamine-Induced Contraction of Human Isolated Umbilical Artery and Its Dependence on Cellular and Extracellular Ca++(ARCH INT PHARMACODYNAMIE, 1991) Doğan, N.; Çiçek, E.; Cenik, A. G.; Sıngırık, E.; Kılıç, M.; Özcan, A. S.The contribution of intra- and extracellular Ca++ during KCl- and 5-hydroxytryptamine-induced contractions was investigated in human isolated umbilical arteries obtained from cords of normal full-term deliveries. In normal solution, nifedipine caused dose-dependent relaxations of the arteries contracted by high K+ (80 mM) and 5-hydroxytryptamine. The IC50 value of nifedipine on KCl-induced contractions was about 9 times lower than that on 5-hydroxytryptamine-induced contractions. In Ca++-free medium, KCl failed to induce contractions of the artery. However, 5-hydroxytryptamine caused contractions amounting to 52 % of the maximum response obtained by re-addition of Ca++, and this response was abolished by 10(-6) M of nifedipine. In the presence of either KCl or 5-hydroxytryptamine, subsequent addition of Ca++ caused reproducible contractions which were also inhibited by nifedipine. These results indicate that the KCl-induced contraction of human isolated umbilical artery is mainly dependent on extracellular Ca++, whereas that induced by 5-hydroxytryptamine involves both intra- and extracellular Ca++. It is also suggested that nifedipine does not only inhibit the influx of extracellular Ca++ during the contraction by 5-hydroxytryptamine but that it may also have intracellular effects.Öğe Effects of Bupivacaine and Ropivacaine on Hemodynamic Parameters in Rabbits(PROUS SCIENCE, SA, 2001) Barışkaner, H.; Tuncer, S.; Ulusoy, H.; Doğan, N.In the present study the toxic effects of ropivacaine and bupiavacaine on the cardiovascular and respiratory systems of rabbits were studied. Both drugs were administered intravenously at doses of 0.5, 1, 2.5, 5 and 10 mu mol/kg. The effects of the two drugs on blood pressure, ECG and respiration rate were evaluated by considering the changes occurring 30 sec after intravenous bolus injection. High doses (5 and 10 mu mol/kg) of bupivacaine and ropivacaine significantly reduced the heart rate and systolic pressure (p < 0.05). Five and 10 mu mol/kg of bupivacaine significantly reduced diastolic pressure (p < 0.05), but only the 10 mu mol/kg dose of ropivacaine had the same effect. Low doses of bupivacaine and high doses of ropivacaine significantly increased the PR interval, QRS duration and QT interval (p < 0.05). The 5 mu mol/kg dose of bupivacaine caused ventricular tachycardia in 3 of 6 rabbits, whereas ropivacaine caused tachycardia in 1 of 5 rabbits. Neither drug had a significant effect on respiration rate or blood gas values (p > 0.05). The results indicate that ropivacaine is less cardiodepressive and arrhythmogenic than bupivacaine.Öğe Effects of Bupivacaine and Ropivacaine on the Isolated Human Umbilical Artery(Churchill Livingstone, 2003) Barışkaner, Hülagü; Tuncer, Sema; Taner, A.; Doğan, N.In this in vitro study on the human umbilical artery, the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME), indomethacin, prazosin, yohimbine and propranolol on the responses induced by bupivacaine and ropivacaine were investigated. Arteries isolated from umbilical cords from women who did not exhibit systemic diseases, who were not on medication and who had normal full-term deliveries, were cut into spiral strips 12 x 3 mm. Strips were mounted in organ baths at 37 degreesC continuously gassed with 5% CO2 in oxygen. The responses to the drugs were recorded isometrically on a polygraph. In the bupivacaine study, when we administered cumulative concentrations of bupivacaine (10(-9)-10(-4) M; n = 6) on basal tonus, there was no relaxation or contraction response on the tissue. Strips were precontracted with serotonin (10(-6) M 5-HT) then bupivacaine (10(-9)-10(-4) M) was directly administered cumulatively. In the ropivacaine group, when cumulative concentrations of ropivacaine (10(-9)-10(-4) M; n = 6) were administered on the tissue, preconstricted with 5-HT, ropivacaine did not alter the contraction response. Ropivacaine (10(-9)-10(-4) M) was directly administered to the bath. Though bupivacaine produced relaxation, ropivacaine produced contraction (P < 0.05). Indomethacin, prazosin, yohimbine and propranolol did not significantly alter these responses. In addition, it was demonstrated that L-NAME did not affect the relaxation responses induced by bupivacaine. Thus adrenergic receptors, nitric oxide syntenaze and prostaglandins do not appear to affect the responses induced by these two local anesthetics.Öğe Effects of Cooling on Contractions of Calf Coronary Artery: Role of the Endothelium(2001) Atalık, Kısmet Esra; Şahin, A. S.; Doğan, N.The effects of cooling on vasoconstrictions induced by contractile agents and role of the endothelium in this effect were analyzed in calf coronary artery. Potassium chloride (KCl, 10-3 - 5 × 102 M), 5-hydroxytryptamine (5-HT, 10-9 - 3 × 10-4 M) and carbachol (10-9 - 3 × 10-4 M) induced concentration-dependent contractions at both 37°C and 28°C (cooling). During cooling the sensitivities, but not the maximal responses to KCl, 5-HT and carbachol were significantly lower than at 37°C. Endothelium removal or NG-nitro-L arginine methyl esther (LNAME, 10-5 M) pretreatment did not modify the effect of cooling. These results suggest that cooling-induced responses in calf coronary artery are independent of endothelium (nitric oxide).Öğe Effects of Deferoxamine on Tissue Lactate and Malondialdehyde Levels in Cerebral Ischemia(Prous Science, Sa , 2003) Barışkaner, Hülagü; Üstün, M. E.; Ak, A.; Yosunkaya, Alper; Doğan, N.; Gürbilek, MehmetIn the present study, the effects of deferoxamine on tissue lactate and malondialdehyde (MDA) levels after cerebral ischemia at rabbits was studied. Rabbits were divided equally, into three groups: group 1: sham-operated group; group 2: cerebral ischemia produced by clamping bilateral common carotid arteries for 60 min: and group 3: deferoxamine 100 mg/kg i.v administered within 5 min after opening the clamps. EEG recordings were obtained in all groups before clamping and in group 2 and 3 60 min after clamping and 60 min after opening the clamps. One hour after opening the clamps and taking EEG recordings, brain cortices were resected and the concentrations of lactate and MDA were determined using the spectrophotometric enzymatic and thiobarbituric acid methods, respectively. There were significant differences between group I and the other groups in MDA and lactate levels (p < 0.05). There were no significant differences in lactate levels between groups 2 and 3. Preischemic EEG grades were the same at till groups. Preischemic (aid postischemic EEG values were significantly different (p < 0.05), but there were no significant differences between postischemic EEG grades in groups 2 and 3. There was also a correlation between postischemic EEG grades and lactate levels, but no correlation between postischemic EEG grades and MDA levels. These results demonstrate that cerebral ischemia leads to an increase in brain tissue lactate and MDA levels and deferoxamine suppresses the increase of MDA, but not lactate. Deferoxamine treatment caused no significant EEG changes. EEG grades correlated well with lactate levels.Öğe Interactions Between Phenylephrine, Clonidine and Xylazine in Rat and Rabbit Aortas(Prous Science, Sa, 2000) Atalık, K. E.; Şahin, A. S.; Doğan, N.The interaction of the a-adrenoceptor agonists clonidine and xylazine with the a-adrenoceptors in the rat and rabbit aortas was investigated. In preparations preconstricted with phenylephrine (10° M), cumulative addition of clonidine and xylazine induced concentration-related vasodilata- tion in the presence of the a-adrenoceptor antagonist yohimbine and the B-blocker propranolol. Neither clonidine nor xylazine treatment inhibited 5-HT- and KCI-induced vasoconstriction. It is concluded that a-agonists have affinity for a-adrenoceptors in rat and rabbit aortas.Öğe Nonadrenergic, Noncholinergic Responses of the Human Colon Smooth Muscle and the Role of K+ Channels in These Responses(PROUS SCIENCE, SA, 2001) Şahin, A. S.; Atalık, K. E.; Günel, E.; Doğan, N.The aim of the present study was to investigate the possible role of notric oxide (NO) as a nonadrenergic, noncholinergic (NANC) mediator in human colon smooth muscle in vitro and to examine its possible interactions with K+ channels. In the presence of atropine (10(-6) M) and guanethidine (10(-5)M).. electrical field stimulation (EFS, 1-10 Hz, 0.3 msec, 50V) for 10 sec induced relaxations which were inhibited by tetrodotoxin (10(-6) M). in the presence of N-G-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), relaxations induced by EFS at 1, 2, 4, 8 and 10 Hz were reduced by 38.7 +/- 4.3, 31.5 +/-3.8, 54.3 +/-5.4, 59.8 +/- 4.5 and 68.6 +/- 5.3% respectively. THe relaxations inhibited by L-NAME were restored by the preincubation of L-argarinine (L-ARG, 10(-3) M) at all frequencies tested. D-Arginine (D-ARG, 10(-3) M) had no effect. Tetraethylammonium (TEA, 10(-4) M) or glibenclamidine (10(-6) M) significantly decreased the relaxations induced induced by EFS. Exogenously applied sodium nitroprusside caused concentration-dependent relaxation with prusside. In conclusion, our data indicate that NO is involved in NANC nerve-mediated relaxation in the human calcium-dependent and ATP-sensitive K+ channels.Öğe Nonadrenergic, Noncholinergic Responses of the Rabbit Detrusor Smooth Muscle and the Role of L-Arginine/Nitric Oxide Pathway in These Responses(Prous Science, Sa, 2000) Şahin, A. S.; Atalık, K. E.; Doğan, N.In the present study, nonadrenergic, noncholinergic (NANC) responses of rabbit detrusor smooth muscle and the possible involvement of the L-arginine/nitric oxide (L-ARG/NO) pathway was investigated. In the presence of atropine (10(-6) M) and guanithidine (10(-5) M), frequency-response curves were obtained by stimulating tissue with 10-sec trains or increasing frequencies (1-10 Hz) with 3-min intervals between stimulations. Electrical field stimulation (EFS) evoked a biphasic response in rabbit detrusor smooth muscle, consisting of an initial contraction followed by relaxation. ATP desensitization significantly inhibited contractions. L-NAME(10(-5) M) increased the contractions by a maximum of 33 +/- 5% at 1 Hz, 37 +/- 5% at 2 Hz, 18 +/- 4% at 4 Hz. 20 +/- 3% at 8 Hz and 15 +/- 4% at 10 Hz. In detrusor preparations, exposure to L-NAME (N-G-nitro-L-arginine methyl ester, 10(-5) M) significantly reduced the maximal relaxation to electrical stimulation to 7 +/- 3% of the control. In the presence of L-ARG (10(-4) M), contractions induced by electrical field stimulation (EFS) at 1, 2, 4, 8 and 10 Hz were reduced by 20 +/- 4, 24 +/- 3, 25 +/- 3, 20 +/- 3 and 30 +/- 5%, respectively. Exposure to L-ARG (10(-4) M) significantly increased the maximal relaxation to electrical stimulation to 52 +/- 5% of the control. Exogenously applied ATP (10(-5)- 10(-2) M) to rabbit detrusor muscle resulted in contractions while sodium nitroprusside (10(-7)-10(-3) M) caused concentration-dependent relaxation. These results suggest that nitric oxide (NO) acts as an inhibitory NANC neurotransmitter in the rabbit detrusor smooth muscle. Additionally, NANC contractions mediated by ATP released from NANC nerves, may be masked by thr L-ARG/NO pathway in this tissue.Öğe Sufentanil ve Remifentanilin İzole Perfüze Rat Böbreği Üzerine Etkileri(2004) Barışkaner, H.; Tuncer, Sema; Otelcioğlu, Ş.; Doğan, N.; Yosunkaya, A.; Kılıç, M.In this in vitro study on isolated perfused rat kidney, the effects of indomethacin, NG-nitro-L arginin methyl ester (L-NAME), propranolol, naloxone, glibenclamide and tetraethylammonium (TEA) on the responses induced by fentanyl, sufentaniyl and remifentanil were investigated. In isolated perfused rat kidney, under a constant flow of 8-10 ml/min, mean basal perfusion pressure and the responses of used inhibitors or antagonists were recorded on a polygraph. Fentanyl (10-9-10-6 M), sufentanil (10 -9-10-6 M) and remifentanil (10-9-10 -6 M) caused a dose-dependent decrease in perfusion pressure raised by submaximum concentration of phenylephrine. Fentanyl induced relaxations were inhibited by glibenclamide (10-5 M, n = 5) and TEA (10-3 M, n = 5) (p < 0.05) but not indomethacin (10-5 M, n = 5), L-NAME (10-4 M, n = 5), propranolol (10-6 M, n = 5) and naloxone (10-6 M, n = 5) (p > 0.05). Both sufentanil- and remifentalin-induced relaxations were not inhibited by indomethacin (10 -5 M, n = 5), L-NAME (10-4 M, n = 5), propranolol (10 -6 M, n = 5), naloxone (10-6 M, n = 5) (p > 0.05) and glibenclamide (10-5 M, n = 5) but TEA (10-3 M, n = 5) was effective (p < 0.05). These results suggest that in isolated perfused rat kidney, K+ channels may play a role in fentanyl-, sufentanil- and remifentanil-induced relaxation by opening ATP sensitive-potassium channels and calcium-activated potassium channels.