Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown that cold perfusion of hearts generates reactive oxygen and nitrogen species (ROS/RNS). In this study, we determined 1) whether ROS scavenging only during cold perfusion before global ischemia improves mitochondrial and myocardial function, and 2) which ROS leads to compromised cardiac function during ischemia and reperfusion (I/R) injury. Using fluorescence spectrophotometry, we monitored redox balance (NADH and FAD), O(2)(*-) levels and mitochondrial Ca(2+) (m[Ca(2+)]) at the left ventricular wall in 120 guinea pig isolated hearts divided into control (Con), MnTBAP (a superoxide dismutase 2 mimetic), MnTBAP (M) + catalase (C) + glutathione (G) (MCG), C+G (CG), and N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) groups. After an initial period of warm perfusion, hearts were treated with drugs before and after at 27 degrees C. Drugs were washed out before 2 h at 27 degrees C ischemia and 2 h at 37 degrees C reperfusion. We found that on reperfusion the MnTBAP group had the worst functional recovery and largest infarction with the highest m[Ca(2+)], most oxidized redox state and increased ROS levels. The MCG group had the best recovery, the smallest infarction, the lowest ROS level, the lowest m[Ca(2+)], and the most reduced redox state. CG and L-NAME groups gave results intermediate to those of the MnTBAP and MCG groups. Our results indicate that the scavenging of cold-induced O(2)(*-) species to less toxic downstream products additionally protects during and after cold I/R by preserving mitochondrial function. Because MnTBAP treatment showed the worst functional return along with poor preservation of mitochondrial bioenergetics, accumulation of H(2)O(2) and/or hydroxyl radicals during cold perfusion may be involved in compromised function during subsequent cold I/R injury.
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PMID:ROS scavenging before 27 degrees C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state. 1728 67

In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar-Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone (10 microM) or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to alpha(1)-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone had no effect on relaxations to ACh in WKY aortae incubated with either L-NAME or methylene blue, but enhanced relaxations to ACh in WKY aortae incubated with indomethacin or partially depolarized with KCl. Relaxations to ACh are totally abolished in both control or flavone pretreated endothelium-denuded WKY aortae. Flavone attenuated the inhibition by beta-NADH of ACh-induced relaxation in WKY aortae, but it had no significant effect on the transient contractions induced by beta-NADH nor the pyrogallol-induced abolishment of ACh-induced relaxation in WKY aortae. Flavone enhanced endothelium-independent relaxation to sodium nitroprusside (SNP) in both endothelium-intact and -denuded WKY aortae. Flavone enhanced relaxation to ACh and SNP as well as attenuated contractile effects to PE in SHR and diabetic aortae, a finding similar to that observed in normal WKY aortae. From these results, we conclude that flavone modulates vascular reactivity in normal as well as hypertensive and diabetic aortae. These effects of flavone results probably through enhanced bioactivity of nitric oxide released from the endothelium.
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PMID:Modulation of vascular reactivity in normal, hypertensive and diabetic rat aortae by a non-antioxidant flavonoid. 1731 9

Acute exposure to the flavonoid baicalein inhibited endothelium-dependent relaxation in physiological arteries, although the mechanisms are not fully understood. We investigated the effect of baicalein on vascular tone in Wistar-Kyoto (WKY) rat isolated aortic rings in the presence and absence of oxidative stress to further determine the underlying mechanisms. Exposure to baicalein (10 microM) completely abolished endothelium-dependent relaxation induced by acetylcholine and attenuated significantly the endothelium-independent relaxation induced by sodium nitroprusside. Baicalein, similar to Nomega-nitro-L-arginine methyl ester (L-NAME, 10 microM), potentiated significantly the contractile response of aortic rings to alpha1-adrenoceptor agonist phenylephrine. In the presence of L-NAME the baicalein effect on phenylphrine contraction or acetylcholine relaxation was unaltered, suggesting that these effects of baicalein are (like L-NAME effect) endothelial nitric oxide synthase (eNOS)/endothelium-derived nitric oxide-dependent. Inhibition of cyclooxygenase activity with indomethacin (10 microM) or scavenging of superoxide anions with superoxide dismutase (150 units/ml), but not scavenging of hydrogen peroxide with catalase (800 units/ml), enhanced significantly by an essentially similar extent the relaxation to acetylcholine in baicalein-pretreated aortic rings. Relaxant effect to acetylcholine was significantly attenuated in control aortic rings, but was completely abolished in baicalein-pretreated aortic rings in the presence of reduced form of beta-nicotinamide adenine di-nucleotide (beta-NADH, 300 microM). Baicalein blocked beta-NADH (300 microM)-induced transient contractions, suggesting that baicalein may have inhibited activity of NADH/NADPH-oxidase. Baicalein did not alter the failure of acetylcholine to induce relaxation in the presence of pyrogallol (300 microM). In summary, acute exposure to baicalein impairs eNOS/endothelium-derived nitric oxide-mediated vascular tone in rat aortas through the inhibition of endothelium-derived nitric oxide bioavailability coupled to reduced bioactivity of endothelium-derived nitric oxide and to cyclooxygenase-mediated release of superoxide anions.
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PMID:Baicalein impairs vascular tone in normal rat aortas: role of superoxide anions. 1744 2

Oxidative stress causes cardiomyocyte death and subsequent ventricular dysfunction and cardiac remodeling after myocardial infarction (MI), thus contributing to high mortality in chronic heart failure patients. We investigated the effects of kallistatin in cardiac remodeling in a chronic MI rat model and in primary cardiac cells. Human kallistatin gene was injected intramyocardially 20 min after ligation of the left coronary artery. At 4 weeks after MI, expression of human kallistatin in rat hearts was identified by reverse transcription-polymerase chain reaction, immunohistochemistry and ELISA. Kallistatin administration improved cardiac performance, increased mean arterial pressure, decreased myocardial infarct size and restored left ventricular wall thickness. Kallistatin treatment significantly attenuated cardiomyocyte size and atrial natriuretic peptide expression. Kallistatin also reduced collagen accumulation, collagen fraction volume and expression of collagen types I and III, transforming growth factor-beta1 (TGF-beta1) and plasminogen activator inhibitor-1 in the myocardium. Inhibition of cardiac hypertrophy and fibrosis by kallistatin was associated with increased cardiac nitric oxide (NO) levels and decreased superoxide formation, NADH oxidase activity and p22-phox expression. Moreover, in both primary cultured rat cardiomyocytes and myofibroblasts, recombinant kallistatin inhibited intracellular superoxide formation induced by H(2)O(2), and the antioxidant effect of kallistatin was abolished by Nomega-nitro-L-arginine methyl ester (L-NAME), indicating a NO-mediated event. Kallistatin promoted survival of cardiomyocytes subjected to H(2)O(2) treatment, and inhibited H(2)O(2)-induced Akt and ERK phosphorylation, as well as NF-kappaB activation. Furthermore, kallistatin abrogated TGF-beta-induced collagen synthesis and secretion in cultured myofibroblasts. This is the first study to demonstrate that kallistatin improves cardiac performance and prevents post-MI-induced cardiac hypertrophy and fibrosis through its antioxidant action.
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PMID:Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction. 1876 77

Nitric oxide (NO) has been implicated in the neuronal hyperexcitability hence its involvement in the pathophysiology of epilepsy is clear. However, some studies indicate that NO has anticonvulsant effects while others present its convulsive effects. In the present study we tested the involvement of NO in pentylenetetrazol (Metrazol) induced Status Epilepticus (SE) rats, using the nonspecific inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) and the neuronal-specific inhibitor, 7-nitroindazole (7N1). The effects of NOS (NO synthase) inhibitors were tested, within the seizures and between them, using the Multiparametric Assembly (MPA) which continuously monitored Cerebral Blood Flow (CBF) by Laser Doppler flowmetry, mitochondrial NADH redox state by the fluorometric technique, extracellular K(+) and H(+) levels using selective mini-electrodes and electrical activity (DC potential and ECoG) using special electrodes. Between seizures a trend of increase in CBF with oxidation of NADH was seen, with no change in K(+) and H(+) extracellular levels. Pre-treatment with L-NAME prevented this trend of increase in CBF whereas the injection of 7NI even decreased CBF between seizures. Within seizures, CBF increased and mitochondrial NADH was oxidized at the first seizures, while in the last seizure NADH was reduced. The use of NOS inhibitors significantly increased the degree of NADH oxidation at the latest convulsions. In conclusion our results demonstrated beneficial effect of NOS inhibitors on the brain cortex under SE induced by Metrazol, implying that they may serve as anticonvulsant drugs.
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PMID:The evaluation of nitric oxide involvement in metrazol induced status epilepticus using multiparametric monitoring. 2123 45


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