The Effects of Diclofenac and Ibuprofen on Heart Function and Oxidative Stress Markers in the Isolated Rat Heart

ABSTRACT Eicosanoids lead to the promotion of inflammation, cause fever and pain and have many other eff ects. NSAIDs block the action of cyclooxygenase (COX) during the process of converting arachidonic acid into inflammatory mediators, thus reducing the symptoms of inflammation. Investigations focusing on nonselective COX inhibitors, used in high doses, revealed harmful eff ects on myocardial function. Th e aim of our study was to assess the eff ects of two nonselective NSAIDs, diclofenac and ibuprofen, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat hearts. Th e hearts of male Wistar albino rats were excised and retrogradely perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cm H2O). Th e experiments were performed under controlled conditions (Krebs-Henseleit physiological solution). Th e hearts were perfused with 10 μmol/l diclofenac and 10 μmol/l ibuprofen. Th e heart function parameters, including the maximum rate of pressure development (dp/dt max), minimum rate of pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean perfusion pressure (MBP) and heart rate (HR), were continuously registered. Coronary flow (CF) was measured flowmetrically. Oxidative stress markers, including the index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO2 -), superoxide anion radical (O2 -), and hydrogen peroxide (H2O2) in the coronary venous effluent, were assessed spectrophotometrically. Our results showed that diclofenac aff ected cardiodynamic parameters more significantly than did ibuprofen. Furthermore, the present data indicate that both estimated COX inhibitors do not promote the production of reactive oxygen species.

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The effects of homocysteine-related compounds on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart

Molecular and Cellular Biochemistry ◽

10.1007/s11010-012-1398-4 ◽

2012 ◽

Vol 370 (1-2) ◽

pp. 59-67 ◽

Cited By ~ 17

Author(s):

Vladimir Zivkovic ◽

Vladimir Jakovljevic ◽

Dusica Djordjevic ◽

Milena Vuletic ◽

Nevena Barudzic ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Heart ◽

Coronary Flow ◽

Cardiac Contractility ◽

Isolated Rat Heart ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Related Compounds ◽

And Oxidative Stress ◽

Isolated Rat

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Effects of DL-Homocysteine Thiolactone on Cardiac Contractility, Coronary Flow, and Oxidative Stress Markers in the Isolated Rat Heart: The Role of Different Gasotransmitters

BioMed Research International ◽

10.1155/2013/318471 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Vladimir Zivkovic ◽

Vladimir Jakovljevic ◽

Olga Pechanova ◽

Ivan Srejovic ◽

Jovana Joksimovic ◽

...

Keyword(s):

Oxidative Stress ◽

Coronary Flow ◽

Cardiac Contractility ◽

Isolated Rat Heart ◽

Oxidative Stress Markers ◽

Homocysteine Thiolactone ◽

Stress Markers ◽

And Oxidative Stress ◽

Isolated Rat

Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μM DL-Hcy TLHC alone or in combination with 30 μM L-NAME, 10 μM DL-PAG, or 10 μM PPR IX. The following parameters were measured:dp/dtmax,dp/dtmin, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2,O2-, and H2O2concentrations. The administration of DL-Hcy TLHC alone decreaseddp/dtmax, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF,O2-, H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increaseddp/dtmax but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease indp/dtmax, SLVP, HR, CF, and TBARS.

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The Effects Of L-Arginine And L-Name On Coronary Flow And Oxidative Stress In Isolated Rat Hearts

Serbian Journal of Experimental and Clinical Research ◽

10.1515/sjecr-2015-0053 ◽

2015 ◽

Vol 16 (4) ◽

pp. 297-304

Author(s):

Tanja Sobot ◽

Amela Matavulj ◽

Vladimir Jakovljevic ◽

Tamara Nikolic ◽

Vladimir Zivkovic ◽

...

Keyword(s):

Oxidative Stress ◽

Experimental Study ◽

Superoxide Anion ◽

Coronary Flow ◽

Anion Radical ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Rat Hearts ◽

And Oxidative Stress ◽

Isolated Rat

AbstractThe aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor) on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g). Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40–120 cmH2O). The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker), superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances). The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol) and L-arginine (1 mmol) + L-NAME (30 μmol). The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts.

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The effects of folic acid and nitric oxide synthase inhibition on coronary flow and oxidative stress markers in isolated rat heart

Molecular and Cellular Biochemistry ◽

10.1007/s11010-006-9381-6 ◽

2006 ◽

Vol 300 (1-2) ◽

pp. 177-183 ◽

Cited By ~ 16

Author(s):

Dragan Djurić ◽

Ana Vušanović ◽

Vladimir Jakovljević

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Folic Acid ◽

Coronary Flow ◽

Isolated Rat Heart ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Oxide Synthase ◽

And Oxidative Stress ◽

Isolated Rat

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Abstract 1378: NFkb Blockade Attenuate Cytokines And Oxidative Stress In The Paraventricular Nucleus And Decreases Neurohumoral Excitation In Spontaneously Hypertensive Rats

Circulation ◽

10.1161/circ.116.suppl_16.ii_283-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Nithya Mariappan ◽

Carrie Elks ◽

Masudul Haque ◽

Philip J Ebnezer ◽

Elizabeth McIIwain ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Paraventricular Nucleus ◽

Spontaneously Hypertensive Rats ◽

Left Ventricular ◽

Oxidative Stress Markers ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Stress Markers ◽

And Oxidative Stress

The transcriptional factor, nuclear factor kappa B (NFkB) plays an important role in the regulation of cytokines. Among the cytokines, tumor necrosis factor-alpha (TNF) plays an important role in cardiovascular pathophysiology. This study was done to determine whether TNF-α blockade with etanercept (ETN) or NFkB blockade with dithiol pyrolidine thiocarbamate (PDTC) attenuate oxidative stress in the paraventricular nucleus (PVN) and contribute to neurohumoral excitation in spontaneously hypertensive rats. Method: Male 20 week old SHR rats were treated with ETN (1 mg/kg BW, sc) or PDTC (100mg/kg BW, ip) for 5 week period. Left ventricular function was measured at baseline (20 weeks) and at 25 weeks using echocardiography. Blood pressure was measured at weekly intervals throughout the study. At the end of the protocol rats were sacrificed the PVN was microdissected for the measurement of cytokines, oxidative stress markers using real time PCR (fold increase compared to WKY controls) and by immunohistochemistry. Superoxide, total reactive oxygen species and peroxynitrite were measured in the PVN and LV using electron paramagnetic resonance. Plasma norepinephrine and epinephrine an indicator of neurohumoral excitation was measured using HPLC-EC. Results: PVN data are tabulated. SHR animals had increased expression of protein and mRNA for cytokines and oxidative stress markers in the PVN and LV with increased MAP and cardiac hypertrophy when compared to WKY rats. Treatment with ETN and PDTC attenuated these increases with PDTC showing marked effect than ETN on hypertrophy and blood pressure responses. Conclusion: These findings suggest that cytokine activation in the PVN contributes to increased oxidative stress and neurohumoral excitation in hypertension.

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Inhibition of gasotransmitters production and calcium influx affect cardiodynamic variables and cardiac oxidative stress in propofol-anesthetized male Wistar rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0719 ◽

2019 ◽

Vol 97 (9) ◽

pp. 850-856 ◽

Cited By ~ 2

Author(s):

M. Djuric ◽

T. Nikolic Turnic ◽

S. Kostic ◽

K. Radonjic ◽

J. Jeremic ◽

...

Keyword(s):

Oxidative Stress ◽

Body Mass ◽

Coronary Flow ◽

Wistar Rats ◽

Calcium Influx ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

Male Wistar Rats ◽

Synthase Inhibitor

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 μmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 μmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmax were noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.

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Tadalafil in Increasing Doses: The Influence on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts

Pharmacology ◽

10.1159/000520498 ◽

2021 ◽

pp. 1-10

Author(s):

Nada M. Banjac ◽

Velibor M. Vasović ◽

Nebojša P. Stilinović ◽

Dušan V. Prodanović ◽

Ana D. Tomas Petrović ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Anion ◽

Coronary Flow ◽

Albino Rats ◽

Dependent Manner ◽

Superoxide Anion Production ◽

Nitrite Oxide ◽

Rat Hearts ◽

And Oxidative Stress ◽

Isolated Rat

Introduction: This study aimed to assess the influence of different doses of tadalafil on coronary flow and oxidative stress in isolated rat hearts. Methods: The hearts of male Wistar albino rats (n = 48) were retrogradely perfused according to the Langendorff technique at gradually increased constant perfusion pressure (CPP) (40–120 mm Hg). Coronary flow and oxidative stress markers: nitrite oxide (NO) outflow and superoxide anion production in coronary effluent were measured. The experiments were performed during control conditions and in the presence of tadalafil (10, 20, 50, and 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 μM). Results: Tadalafil administration significantly increased coronary flow at all CPP values at all administered doses. Tadalafil led to an increase in the NO levels, but a statistically significant NO release increase was found only at the highest dose and highest CPP. Tadalafil did not significantly affect the release of O2−. After inhibiting the nitrite oxide synthase system by L-NAME, tadalafil-induced changes in cardiac flow and NO levels were reversed. L-NAME administration had no pronounced effect on the O2− release. Conclusion: Tadalafil causes changes in the heart vasculature in a dose-dependent manner. It does not lead to a significant increase in the production of superoxide anion radicals.

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The Effects of Potassium Cyanide on the Functional Recovery of Isolated Rat Hearts after Ischemia and Reperfusion: The Role of Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/5979721 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Anica M. Petkovic ◽

Vladimir Lj. Jakovljevic ◽

Jovana V. Bradic ◽

Jovana N. Jeremic ◽

Nevena S. Jeremic ◽

...

Keyword(s):

Cytochrome C ◽

Functional Recovery ◽

Heart Function ◽

Potassium Cyanide ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Global Ischemia ◽

Albino Rats ◽

Rat Hearts ◽

Isolated Rat

This investigation is aimed at examining the effects of pharmacological PostC with potassium cyanide (KCN) on functional recovery, gene expression, cytochrome c expression, and redox status of isolated rat hearts. Rats were divided into the control and KCN groups. The hearts of male Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure of 70 cmH2O. After stabilisation, control hearts were subjected to global ischemia (5 minutes), followed by reperfusion (5 minutes), while experimental hearts underwent global ischemia (5 minutes) followed by 5 minutes of reperfusion with 10 μmol/L KCN. The following parameters of heart function were measured: maximum and minimum rates of pressure development, systolic and diastolic left ventricular pressure, heart rate, and coronary flow. Levels of superoxide anion radical, hydrogen peroxide, nitrites, and index of lipid peroxidation (measured as thiobarbituric acid-reactive substances) were measured in coronary venous effluent, and activity of catalase was determined in heart tissue. Expression of Bax, Bcl-2, SOD-1, SOD-2, and cytochrome c was studied as well. It was shown that expression of Bax, Bcl-2, and SOD-2 genes did not significantly differ between groups, while expression of SOD-1 gene and cytochrome c was lower in the KCN group. Our results demonstrated that KCN improved the recovery of myocardial contractility and systolic and diastolic function, enhanced catalase activity, and diminished generation of prooxidants. However, all possible mechanisms and potential adverse effects of KCN should be further examined in the future.

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