Ziya Kaygisiz

Eskisehir Osmangazi University, Eskişehir, Eskisehir, Turkey

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Publications (20)16.18 Total impact

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    ABSTRACT: Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.
    Acta Physiologica Hungarica 12/2010; 97(4):362-74. · 0.88 Impact Factor
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    ABSTRACT: There are evidences that proadrenomedullin N-terminal 20 peptide (PAMP) and calcitonin may be involved in cardiovascular function. Therefore, we studied effects of rat PAMP and human PAMP as well as rat calcitonin and salmon calcitonin on coronary perfusion pressure, heart rate and contractile force. Isolated rat hearts were perfused under constant flow condition and rat PAMP (1.10 and 100 nM), human PAMP (1,10 and 100 nM), rat calcitonin (10.100 and 1000 nM) or salmon calcitonin (10.100 and 1000 nM) were infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and +dP/dtmax were measured. Statistical analysis was performed using repeated measures ANOVA and Bonferroni posthoc tests. Rat PAMP (1.10 and 100 nM) did not alter perfusion pressure. However, it increased heart rate from 257.83+/-23.89 to 282+/-24.98 beats/min (p<0.001), from 259.83+/-25.05 to 289.8+/-19.5 beats/min (p<0.001) and from 249.66+/-19.19 to 280.50+/-25.26 beats/min (p<0.001) for 1.10 and 100 nM, respectively. Rat PAMP decreased left ventricular developed pressure from 90.5+/-18.5 to 79+/-15.3 mmHg (p<0.05), from 88.00+/-10.12 to 73.00+/-12.38 mmHg (p<0.05) and from 79.83+/-8.98 to 64.83+/-10.12 mmHg (p<0.05) for 1.10 and 100 nM, respectively. The peptide also decreased +dP/dtmax from 3710.5+/-370.6 to 3223.8+/-261.1 mmHg s-1 (p<0.001), from 3683.16+/-327.27 to 3040.6+/-423.8 mmHg s-1 (p<0.01) and from 3746.16+/-315.76 to 3009.83+/-204.64 mmHg s-1 (p<0.001) for 1.10 and 100 nM, respectively. Rat calcitonin (10.100 and 1000 nM) did not change perfusion pressure but it decreased heart rate from 269.16+/-22.6 to 253.6+/-22.84 beats/min (p<0.05), from 263.8+/-27.3 to 247.00+/-36.63 beats/min (p<0.05) and from 285.0+/-32.4 to 264.00+/-39.83 beats/min (p<0.01) for 10.100 and 1000 nM, respectively. Rat calcitonin did not significantly affect left ventricular developed pressure. Human PAMP or salmon calcitonin did not change perfusion pressure, heart rate and left ventricular developed pressure. We conclude that rat PAMP may induce positive chronotropic and negative inotropic effect while rat calcitonin may produce a negative chronotropic effect. Human PAMP or salmon calcitonin could not alter perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.
    Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 06/2009; 9(3):176-82. · 0.72 Impact Factor
  • O Azboy, Z Kaygisiz
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    ABSTRACT: The effect of sleep deprivation on male runners (age 18.1 +/- 0.35) and volleyball players (age 17.8 +/- 0.36) has not been investigated. Therefore, we studied the possible effect of sleep deprivation in the sportsmen. The athletes performed spirometric tests at rest and then incremental exercise test on ergometer following one night sleep and one night (25-30 h) sleeplessness. Several standard measurements of spirometric function showed no significant change following sleep loss. Sleep loss raised resting oxygen uptake (VO2) in the runners and resting carbon dioxide production (VCO2) in both the runners and the volleyball players (p < 0.05). However, it left heart rate (HR), respiratory quotient (R), minute ventilation (VE) and arterial oxygen saturation (SaO2) unchanged at rest in both groups. Sleep loss decreased time to exhaustion in the volleyball players (p < 0.01). In the runners and the volleyball players, sleep loss did not alter exercise values of HR, VO2, VCO2, R and SaO2, but it reduced exercise VE (p < 0.05). We suggest that one night sleep deprivation may reduce exercise performance by decreasing exercise VE and time to exhaustion. We also indicate that sleep loss may decrease more the performance of volleyball players than that of runners.
    Acta Physiologica Hungarica 03/2009; 96(1):29-36. · 0.88 Impact Factor
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    ABSTRACT: Quercetin is an important member of dietary flavonoid family and widely present in red wine and Mediterranean diet. The major objective of the this study is to evaluate the beneficial effects of quercetin in protecting the myocardium from the deleterious effects of ischemia reperfusion (I/R) injury in chronic quercetin treatment with or without an acute quercetin infusion protocols. Forty male Sprague-Dawley rats were included in this experimental randomized study/ Langendorff perfused isolated rat hearts were subjected to 60-min of global ischemia period following 60-min of reperfusion. All animals were randomly divided into 4 groups. Group 1 animals were kept as controls. Group 3 and 4 animals received 50 mg/kg quercetin via an intragastric tube for 7 days for chronic treatment. Group 2 and 4 animals received an acute 15 mmol/L infusion for 30 minutes before the onset of ischemia. The myocardial postischemic recovery was compared using hemodynamic data (peak systolic pressure, end-diastolic pressure and +dP/dtmax), coronary flow, biochemical parameters (lactate dehydrogenase, creatine kinase-MB fraction, cardiac troponin I) from coronary effluent, and oxidative stress markers (malondialdehyde, glutathione, glutathione reductase and nitrite) from heart tissue homogenates in each group. Quercetin has provided increased preservation in myocardial recovery in both chronic and acute treatment protocols compared to non-treated group. According to all estimated hemodynamic parameters, while the statistical difference between acute treated hearts and control hearts was significant (p<0.05); this significance was more clear in chronic treated groups (group 3 and 4) when compared to control (p<0.01). Likewise, biochemical and oxidative stress markers displayed significant differences in acute treated and chronic treated hearts when compared to control (p<0.05 and p<0.01, respectively). As a major dietary flavonoid, due to its antioxidant and cytoprotective actions, quercetin has the capacity to protect the myocardial tissue against global ischemia and reperfusion injury. In instances where the molecule is administered for the purpose of acute therapy, this cardioprotective effect of a significant degree can be observed to; however, this potency is further accentuated upon administration as a chronic treatment protocol for seven days.
    Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 12/2007; 7(4):404-10. · 0.72 Impact Factor
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    ABSTRACT: The aim of the present study was to evaluate the effect of tramadol on isolated rat hearts subjected to global ischemia-reperfusion injury. Langerdorff perfused isolated rat hearts were subjected to 60 min of global ischemia following 60 min of reperfusion. In group I and III hearts were received tramadol before the onset of ischemia. Following the ischemic period, group II and III hearts were received tramadol infusion. Group I and IV hearts were subjected to saline at the same time point. The myocardial postischemic recovery was compared using hemodynamic, coronary flow, biochemical parameters from coronary effluent, and oxidative stress markers from heart tissue homogenates. There were significant differences between tramadol and saline used groups in hemodynamic parameters. GPx values of groups I and III were significantly lower than group IV (p<0.05). SOD values of groups I, II and III were higher than group IV (p<0.05). LDH values of groups I and II were significantly lower than groups III and IV (p<0.05). Tramadol provides a cardioprotective effect against myocardial ischemia-reperfusion in isolated rat heart.
    Scandinavian Cardiovascular Journal 08/2007; 41(4):242-7. · 0.82 Impact Factor
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    ABSTRACT: Ischemia and reperfusion injury of the skeletal muscle is a common and serious condition observed in patients admitting to peripheral vascular surgery, interventional radiology and cardiology departments. Resveratrol (RVT) being a strong natural antioxidant is found in deal of red wine and Mediterranean diet. In the present study, male Spraque-Dawley rats were randomized into two groups of equal size. The first group was the control group, and these rats were administered with tap water with a gastric tube for fourteen consecutive days once daily. According to the same protocol, the rats in the second group were treated with tap water containing 20 mg/kg RVT. All the rats in the two groups were subjected to acute hind limb ischemia through clamping of the abdominal aorta for 120 min. Following this procedure, 60 minutes of reperfusion was applied by reestablishing blood flow in both iliac arteries. Ischemic damage in the skeletal muscle tissue was assessed by measuring myoglobin, lactate dehydrogenase, creatinine phosphokinase, aspartate transaminase enzymes in venous blood samples obtained at the end of the reperfusion period. Oxidative stress caused by reperfusion was determined by measuring MDA, carbonyl and protein sulphydryl levels in quadriceps muscle tissue retrieved at the end of the experiment. In Group II rats, all the measured ischemic enzymes and the markers of oxidative stress reflected robust anti-ischemic properties obtained by RVT administration. The data from both groups revealed statistically significant protection against acute skeletal muscle ischemia and reperfusion injury in Group II rats, compared to Group I. As a major dietary flavonoid RVT can protect the skeletal muscle tissue against global ischemia and reperfusion injury because of its strong antioxidant and cytoprotective properties.
    The Chinese journal of physiology 09/2006; 49(4):204-9. · 0.75 Impact Factor
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    ABSTRACT: Diabetes mellitus (DM) is a major predisposing factor for ischemic heart disease. Metabolic disturbances in diabetic heart including impaired myocardial glucose uptake and elevated plasma free fatty acids and increased rate of fatty acid beta-oxidation are probably important contributing factors to greater mortality. Trimetazidine (TMZ), a well-studied anti-ischemic agent, has been demonstrated to be beneficial in treatment of coronary artery disease as well as in treatment of diabetic patients. However, studies reporting the effects of the drug against global myocardial ischemia/reperfusion injury, particularly in diabetic hearts, are rare. This study was mainly aimed to investigate the cardioprotective action of TMZ against global ischemia in diabetic hearts and to compare its protective efficiency level with non-diabetics. Twenty streptozotocin-induced diabetic and 20 non-diabetic rats were divided into two groups each. Group I (diabetic, n = 10) and group III (non-diabetic, n = 10) rats were given saline in both pretreatment and acute treatment protocols and reserved as control groups. Group II (diabetic, n = 10) and group IV (non-diabetic, n = 10) rats were both pretreated orally with 3 mg/kg TMZ twice daily for 5 days and treated with TMZ infusion at a concentration of 10(-6) M for 30 min during the experiment. Isolated hearts from each rat were submitted to Langendorff perfusion and a period of 60 min of global ischemia following 60 min of reperfusion. Myocardial post-ischemic recovery was compared in each group using hemodynamic data (peak systolic pressure, end diastolic pressure, +dP/dt(max)), coronary flow, biochemical parameters (CK-MB, cTnT) from coronary effluent, and obtained data were statistically analyzed by both MANOVA and two-sample Hotelling's T2 tests. Both hemodynamic and biochemical findings signaled a significantly enhanced myocardial recovery provided by TMZ treatment in diabetic and non-diabetic hearts as compared to non-treated hearts. Although efficiency level of TMZ on mechanical recovery was not different between diabetics and non-diabetics, the protective action of TMZ on myocardial damage measured by biochemical parameters was more evident in diabetic hearts than in non-diabetics. Shifting myocardial energy metabolism away from fatty acids toward glucose oxidation and regulating transmembrane ion disturbances by TMZ can be considered as an appropriate adjunctive treatment in diabetics, especially in patients undergoing open-heart surgery who will be exposed to global myocardial ischemia.
    Archives of Medical Research 09/2006; 37(6):700-8. · 2.08 Impact Factor
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    ABSTRACT: To compare the inotropic and chronotropic effects of ropivacaine and bupivacaine in an isolated, spontaneously beating rat heart, and to determine the reversal effects of dopexamine on these effects. The study was conducted at the Department of Physiology, Medical Faculty, Osmangazi University, Eskisehir, Turkey in November 2001. Fifty animals were randomly assigned to 5 groups. Hearts were perfused with a modified Krebs Henseleit solution. In group I (n=10) hearts were exposed to bupivacaine 5 x 10-6 M and in group II (n=10) hearts were exposed to ropivacaine 5 x 10-6 M for 15 minutes. Group III (n=10) was the dopexamine control group and hearts were exposed to dopexamine 1 x 10-6 M for 5 minutes. In group IV (n=10) and in group V (n=10) hearts were exposed to dopexamine in 1 x 10-6 M doses immediately after the bupivacaine and ropivacaine infusions. Heart rates and contractile forces were recorded continuously during the study. Both of the local anesthetics had cardiac depressant effect on isolated hearts. Bupivacaine created more significant effect on heart rate and contractility than ropivacaine. Hearts receiving dopexamine after the infusion of local anesthetic, recovered more quickly. Bupivacaine had more depressant effects on cardiac contractility and chronotropy than ropivacaine. Dopexamine may provide an alternative to presently recommended pharmacological therapy in cases of bupivacaine and ropivacaine induced cardiotoxicity. But, the clinical impact of the use of dopexamine in this situation deserves further evaluation.
    Saudi medical journal 09/2006; 27(8):1194-8. · 0.62 Impact Factor
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    ABSTRACT: There is enough evidence that erythropoietin (EPO) may be involved in cardiovascular function. Therefore we have investigated the possible effects of EPO on left ventricular developed pressure, +dP/dt(max), heart rate, tissue cAMP, and nitrite levels. Isolated rat hearts were perfused under constant flow (10 ml/min) conditions with modified Krebs-Henseleit solution and recombinant human erythropoietin at doses of 100, 200, 500, and 1,000 IU/kg was administered as bolus injections. EPO at 100 IU/kg decreased, but higher doses (500 and 1,000 IU/kg) raised the developed pressure and +dP/dt(max). However, it did not affect heart rate or coronary perfusion pressure when all the respective doses were applied. EPO at 100 IU/kg increased nitrite, and at 1,000 IU/kg it raised cAMP. Our results suggest that EPO may produce dose-dependently negative and positive inotropic effects on myocardial contractility in isolated rat hearts. NO and cAMP may be involved in negative and positive inotropic effects of EPO, respectively.
    The Journal of Physiological Sciences 07/2006; 56(3):247-51. · 1.09 Impact Factor
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    ABSTRACT: The major objective of the present study is to evaluate the potential role of resveratrol (RVT), a natural antioxidant found in grapes and red wine, in protecting the myocardium from the deleterious effects of ischemia-reperfusion (I/R) injury using isolated rat hearts. Langendorff perfused isolated rat hearts were subjected to 60 min of global ischemia following 60 min of reperfusion. RVT was given according to chronic pretreatment and/or acute treatment protocols. Animals received RVT at the dose of 20 mg/kg via an intragastric tube for 14 days before the experiment and/or at the infusion concentration of 10 microM for 30 min before the onset of ischemia. The myocardial postischemic recovery was compared using hemodynamic data (peak systolic pressure, end diastolic pressure, and +dP/dtmax), coronary flow, biochemical parameters (LDH, CK-MB, cTnI, myoglobin) from coronary effluent, and oxidative stress markers (MDA, GSH, carbonyl) from heart tissue homogenates in each group. RVT pretreatment and treatment protocols have provided increased preservation in myocardial recovery following global ischemia compared to a non-treated group. Furthermore, the ischemic damage of myocardium was significantly lower in chronic pretreated rats than in the acutely treated group. In contrast, no significant difference was observed in cardioprotective effects of RVT between the only pretreated group, and both the pretreated and treated group throughout reperfusion. The findings from this study indicate that RVT has potent cardioprotective properties against I/R injury in rat hearts. The study also highlighted that the administration of RVT, as pretreatment, has amplified the beneficial effects over the standard treatment.
    Scandinavian Cardiovascular Journal 09/2004; 38(4):245-54. · 0.82 Impact Factor
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    ABSTRACT: The purpose of the study was to investigate the effects of one night's sleep deprivation on the cardiorespiratory responses to exercise during the follicular and luteal phases of the menstrual cycle. We have studied nine, healthy females aged 24-35 years with regular menstrual cycles. Each subject performed spirometric tests at rest and then an incremental exercise testing during 11-13 days of follicular phase and 22-24 days of luteal phase following one normal night's sleep or one night's sleep loss. Compared with resting values exercise produced significant increases in cardiorespiratory variables including oxygen uptake (VO2), carbon dioxide production (VCO2), tidal volume (VT), respiratory rate (RR), minute ventilation (VE), systolic blood pressure, heart rate (HR) and respiratory quotient (R). However, it did not alter significantly diastolic blood pressure, end-tidal PO2 (PETO2), end-tidal PCO2 (PETCO2) and arterial oxygen saturation (SaO2). Spirometric variables which include forced vital capacity (FVC), forced expiratory volume in one s (FEV1), FEV1/FVC%, forced expiratory volume in three s (FEV3), forced expired flow from 25-75% of FVC (FEF 25-75%), forced expired flow at 25% of FVC (FEF 25%), forced expired flow at 50% of FVC (FEF 50%), forced expired flow at 75% of FVC (FEF 75%), forced expired flow from 75-85% of FVC (FEF 75-85%), peak expiratory flow (PEF), expiratory reserve volume (ERV), inspiratory capacity (IC) and maximal voluntary ventilation (MVV) and cardiorespiratory variables were not different between the cycle phases after one normal night's sleep or one night's sleep deprivation. Neither menstrual cycle phase nor sleep deprivation affected spirometric and cardiorespiratory parameters. We suggest that one night's sleep deprivation does not produce alterations in spirometric parameters and cardiorespiratory responses to submaximal incremental exercise during the follicular and luteal phases.
    Indian journal of physiology and pharmacology 08/2003; 47(3):279-87.
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    ABSTRACT: The effect of human adrenomedullin, human amylin fragment 8-37 (amylin 8-37) and rat calcitonin gene-related peptide (CGRP) on contractile force, heart rate and coronary perfusion pressure has been investigated in the isolated perfused rat hearts. Adrenomedullin (2x10(-10), 2x10(-9) and 2x10(-8) M) produced a significant decrease in contractile force and perfusion pressure, but only the peptide caused a decline in heart rate at the highest dose. Amylin (10(-9), 10(-8) and 10(-7) M) significantly increased and then decreased contractile force. Two doses of amylin (10(-8) and 10(-7) M) induced a significant increase in heart rate, however amylin did not change perfusion pressure in all the doses used. Rat alpha CGRP (10(-8), 10(-7) and 10(-6) M) evoked a slight decline in contractile force following a significant increase in contractile force induced by the peptide. CGRP in all the doses raised heart rate and lowered perfusion pressure. Our results suggest that adrenomedullin has negative inotropic, negative chronotropic and coronary vasodilator actions. Amylin produces a biphasic inotropic effect and evokes a positive chronotropy. CGRP causes positive inotropic, positive chronotropic and vasodilatory effects in isolated rat hearts.
    Acta Physiologica Hungarica 02/2003; 90(2):133-46. · 0.88 Impact Factor
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    N Erkasap, E Ates, S Erkasap, Z Kaygisiz
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    ABSTRACT: Previous studies have reported a decreased incidence of delayed graft function after cadaveric transplantation with the use of lidocaine pretreatment of the donor. We evaluated the effects of lidocaine on prolonged cold ischemia and reperfusion injury in a canine model of isolated kidney perfusion (IPK). The purpose of this study was to evaluate the renal function of isolated perfused canine kidneys after 48 h of cold storage with Euro-Collins (EC) solution or EC solution plus lidocaine. Isolated perfused canine kidneys were randomized into four groups which contained six kidneys: I) cold flush with EC solution and immediately reperfused, II) cold flush with EC solution plus lidocaine and immediately reperfused, III) 48 h of cold storage with EC and reperfusion, IV) 48 h of cold storage with EC solution plus lidocaine and reperfusion. The measured renal functions were glomerular filtration rate, urine production, perfusate flow, urinary lactic dehydrogenase (ULDH), Na reabsorptive capacity, and tissue MDA levels. Histological examination was performed after reperfusion. The tubular functions of kidneys preserved with EC solution containing lidocaine were better when compared with the kidneys preserved with EC alone. Tubular injury marker levels (ULDH) in group IV were significantly lower than in group III and lidocaine also reduced lipid peroxidation during reperfusion. This is in agreement with the histological results. The results of the present study can be taken as evidence of the cytoprotective effect of lidocaine, which may therefore be accepted as a useful agent for kidney preservation.
    Physiological research / Academia Scientiarum Bohemoslovaca 02/2002; 51(5):493-9. · 1.53 Impact Factor
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    ABSTRACT: The roles of cGMP, prostaglandins, the entry of extracellular Ca2+ through slow channels, endothelium and V1 receptors in the negative inotropic, chronotropic and coronary vasoconstrictor responses to arginine vasopressin (AVP) have been investigated in isolated perfused rat hearts. The bolus injection of 5 x 10(-5) M AVP produced a significant decrease in contractile force, heart rate and coronary flow. AVP also significantly decreased contractile force, heart rate and coronary flow in hearts pretreated with an inhibitor of soluble guanylate cyclase methylene blue (10(-6) M), an effective drug for removing endothelium saponin (500 micrograms/ml), an inhibitor of cyclooxygenase indomethacin (10(-5) M) or a calcium channel antagonist verapamil (5 x 10(-7) M). The potent V1 receptor antagonist [Deamino-Pen1, Val4, D-Arg8]-vasopressin (9 x 10(-5) M) did not alter effects of AVP but the very potent V1 receptor antagonist [beta-Mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin (8 x 10(-5) M) abolished these effects. Our results suggest that AVP produces negative inotropic, chronotropic and coronary vasoconstrictor effects in isolated perfused rat hearts. cGMP, prostaglandin release and Ca2+ entry does not involve in the effects of AVP. These effects are endothelium independent and mediated by V1 receptors. The use of V1 receptor antagonist [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin may be beneficial for preventing the negative inotropy, chronotropy and coronary vasoconstriction induced by AVP.
    Indian journal of physiology and pharmacology 02/2001; 45(1):54-62.
  • S Ateş, Z Kaygisiz
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    ABSTRACT: The involvement of nitric oxide (NO), muscarinic receptors, prostaglandins, calcium influx via slow calcium channels, Ca2+ release from intracellular stores, protein kinase C, and endothelium in the positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of acetylcholine (ACh) has been investigated in isolated rat hearts. The perfusion of hearts with ACh (10(-7), 5 x 10(-7), and 10(-6) M) produced marked decreases in heart rate and coronary flow and a marked increase in contractile force. Similar effects have been observed during the perfusion of hearts with ACh in the presence of Nomega-nitro-L-arginine methyl ester (L-NAME), which is an inhibitor of NO synthesis. The positive inotropic, negative chronotropic, and coronary vasoconstrictor effects of ACh were abolished by muscarinic receptor blocker atropine. In hearts pretreated with cyclooxygenase inhibitor indomethacin, ACh significantly decreased heart rate but did not significantly affect coronary flow and contractile force. In the presence of calcium channel antagonist verapamil or protein kinase C inhibitor staurosporine, ACh produced a significant drop in heart rate but did not significantly affect coronary perfusion pressure and force of contraction. In the presence of the inhibitor of the release of Ca2+ from intracellular stores dantrolene sodium, ACh produced a significant increase in coronary perfusion pressure and a marked decline in heart rate, but did not significantly affect force of contraction. Furthermore, the disruption of endothelium by perfusing the hearts with saponin abolished the vasoconstrictor effect of ACh but did not alter negative chronotropic and positive inotropic effect. Our results suggest that ACh causes vasoconstrictor, negative chronotropic, and positive inotropic effects in isolated rat hearts. Cardiac effects of ACh are related to muscarinic receptor activation, and prostaglandins modulate ACh-induced vasoconstriction and positive inotropy. Our data also suggest that protein kinase C and calcium influx from extracellular source may be responsible for the vasoconstrictor and positive inotropic effect of ACh. The calcium release from intracellular stores may mediate the positive inotropic effect, and the vasoconstrictor effect of ACh depends on an intact endothelium.
    The Japanese Journal of Physiology 01/1999; 48(6):483-91. · 1.04 Impact Factor
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    ABSTRACT: The machanisms that mediate the actions of bradykinin on ureteral motility are poorly defined and mediation via prostaglandins has not been examined. Therefore, the effects of bradykinin on contractility and the possible mediator role of prostaglandins have been investigated in sheep ureter. At the concentrations of 10-8, 10-7 and 10-6M, bradykinin elicited marked reductions in contractile force. When ureteral strips were treated separately with 10-6M indomethacín, 2x10-6M sodium salicylate and 10-5 M aspirin, each drug produced a significant decrease in contractile force. In strips in which prostaglandin synthesis was inhibited by the above concentrations of indomethacin, sodium salicylate and aspirin, 10-7M bradykinin significantly decreased the contractility. From these data, we concluded that in ureter bradykinin decreases contractility via a mechanism not involving prostaglandin generation.
    Kidney and Blood Pressure Research 01/1995; 18(1):49-55. · 1.60 Impact Factor
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    ABSTRACT: The effects of 50 microM lanthanum (La3+) on the contractile force, rate and coronary flow of rat hearts perfused with solutions containing 2.5, 5, 7.5 mM calcium (Ca2+) have been investigated. La3+ produced a rapid and marked decrease in contractile force within 1-3 min ("early La(3+)-effect"). The inhibition of contractility by La3+ was reduced progressively when the Ca2+ ion concentration in the perfusion fluid was raised from 2.5 to 7.5 mM. However, after 10-80 min of La3+ perfusion the contractile force was increased significantly ("late La(3+)-effect"). Elevation of Ca2+ during exposure to La3+ increased its effect. During the late La(3+)-effect, a marked decrease in heart rate and a significant increase in time to reach peak tension, time for half relaxation and twitch duration was observed. High concentrations of perfusate Ca2+ decreased the chronotropic response to La3+, in contrast, elevated Ca2+ potentiated La(3+)-induced increase in time to reach peak tension, time for half relaxation and twitch duration. La3+ produced a significant decrease in coronary flow. High Ca2+ augmented the decrease coronary flow. The findings indicate that La3+ may produce marked effects on myocardial function. High extracellular Ca2+ reduces the La(3+)-induced initial decrease in force of contraction, but potentiates the late increase in contractile force by La3+. Elevated external Ca2+ also increases the effects of La3+ on twitch parameters, heart rate and coronary flow.
    Acta Physiologica Hungarica 02/1991; 78(2):191-200. · 0.88 Impact Factor
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    ABSTRACT: The mechanisms that mediate the actions of bradykinin on ureteral motility are poorly defined and mediation via prostaglandins has not been examined. Therefore, the effects of bradykinin on contractility and the possible mediator role of prostaglandins have been investigated in sheep ureter. At the concentrations of 10(-8), 10(-7) and 10(-6) M, bradykinin elicited marked reductions in contractile force. When ureteral strips were treated separately with 10(-6) M indomethacin, 2 x 10(-6) M sodium salicylate and 10(-5) M aspirin, each drug produced a significant decrease in contractile force. In strips in which prostaglandin synthesis was inhibited by the above concentrations of indomethacin, sodium salicylate and aspirin, 10(-7) M bradykinin significantly decreased the contractility. From these data, we concluded that in ureter bradykinin decreases contractility via a mechanism not involving prostaglandin generation.
    Renal physiology and biochemistry 18(1):49-55.
  • Z Kaygisiz, S H Erden
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    ABSTRACT: The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function under basal conditions and when exposed to nifedipine was studied in perfused rat hearts. Inhibition of basal release of NO by bolus injections of NG-nitro-L-arginine (L-NNA) (90 mM) and NG-nitro-L-arginine methyl ester (L-NAME) (185, 370 and 740 mM) induced significant decrease in coronary flow, contractile force and heart rate. L-NAME in the doses of 185, 370 and 740 mM also decreased significantly contractile force and heart rate during treatment with 170 microM nifedipine. However, the same doses of L-NAME caused an insignificant reduction in coronary flow in the presence of nifedipine. These findings suggest that NO has an important role in the regulation of coronary flow and mechanical performance under basal conditions and during the hearts exposed to nifedipine. Nifedipine may attenuate the myocardial ischaemia induced by the loss of NO production.
    Acta Physiologica Hungarica 85(2):163-74. · 0.88 Impact Factor