Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of tyramine on the production of adenosine in rat heart. A flexibly mounted microdialysis setup was used to measure the concentration of interstitial adenosine and to assess the activity of ecto-5'-nucleotidase in in vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and perfused with Tyrode solution containing adenosine 5'-monophosphate (AMP) at a rate of 1.0 microl/min. The concentration of adenosine in the effluent (dialysate) was measured by high-performance liquid chromatography (HPLC). Dialysate adenosine obtained during perfusion with the AMP-containing solution through the probe originated from the hydrolysis of AMP by endogenous ecto-5'-nucleotidase, and the level of adenosine reflected the activity of ecto-5'-nucleotidase in the tissue. Tyramine (0-4 mM) increased the adenosine concentration measured during the perfusion of AMP (100 microM) in a concentration-dependent manner. Alpha,beta-methyleneadenosine 5'-diphosphate (alpha,beta-meADP, 100 microM), an inhibitor of ecto-5'-nucleotidase, abolished the AMP-induced increase in dialysate adenosine. Tyramine (1 mM) increased the adenosine concentration measured in the presence of 100 microM AMP (i.e., the activity of ecto-5'-nucleotidase) by 65.8 +/- 19.9% (n = 6, P < 0.05), an increase which was inhibited by an antagonist of the alpha1-adrenoceptor (prazosin, 50 microM) or of protein kinase C (chelerythrine, 10 microM). These data provide the first evidence that alpha1-adrenoceptor stimulation and the subsequent activation of protein kinase C can increase adenosine concentrations in the interstitial space of ventricular muscle in vivo, through activation of endogenous ecto-5'-nucleotidase. To examine the effect of tyramine on the production of adenosine by ischemia-reperfusion of the rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery. When the heart was reperfused, elevation of the level of adenosine in the ischemic zone was observed, but this change was not significant. However, when corresponding experiments were performed with a subsequent systemic administration of tyramine (1 mM), a marked elevation in the level of adenosine was observed. The results suggest that tyramine elevates adenosine via stimulation of alpha1-adrenoceptors and protein kinase C-mediated activation of ecto-5'-nucleotidase in rat heart.
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PMID:Tyramine produces interstitial adenosine-mediated activation of ecto-5'-nucleotidase in rat heart in vivo. 1042 37

The present study examined whether tyramine-induced hydroxyl radical (*OH) generation via noradrenaline release was attenuated by prazosin. A flexibly mounted microdialysis technique was used to detect the generation of *OH in in vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anaesthetized rats and Ringer's solution was used. To measure the level of *OH, sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused directly through a microdialysis probe to detect the generation of *OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Tyramine (0.1, 0.5 and 1.0 mM) increased the level of 2,3-DHBA in a concentration-dependent manner. However, in the presence of prazosin (10 microM), the effect of tyramine was abolished. To confirm the generation of *OH by a Fenton type reaction, iron (II) was infused through a microdialysis probe. A positive linear correlation between iron (II) and the formation of 2,3-DHBA (R2 = 0.982) was observed. To examine the effect of prazosin on ischemic/reperfused rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery. When the heart was reperfused, a marked elevation of the level of 2,3-DHBA was observed. However, in the presence of prazosin (10 microM), the elevation of 2,3-DHBA was not observed in ischemic/reperfused rat heart. Prazosin was shown to have a *OH scavenging effect. These results suggest that tyramine-induced noradrenaline causes *OH generation, an effect which is inhibited by prazosin as Na+ channel blocker, but not through its alpha1-adrenoceptor antagonistic action of prazosin.
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PMID:Prazosin attenuates hydroxyl radical generation in the rat myocardium. 1049 2

We used a flexibly mounted microdialysis technique to the hearts of rats and examined the protective effect of imidaprilat, an angiotensin-converting enzyme (ACE) inhibitor, on the production of hydroxyl free radical (*OH) generation. A microdialysis probe was implanted into the left ventricular myocardium, and dialysate norepinephrine (NE) concentrations were measured as an index of myocardial interstitial NE levels. Sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was directly infused through a microdialysis probe to detect the generation of *OH reflected by the formation of dihydroxybenzoic acid (DHBA) in rat myocardium. When tyramine (1 mM) was directly infused through the microdialysis probe, the level of NE significantly increased in the dialysate and the level of NE increased by 128 +/- 43%. Imidaprilat (5, 25 and 50 microM) decreased the level of tyramine (1 mM)-induced NE in a concentration-dependent manner. Tyramine clearly produced an increase in *OH formation. In the presence of imidaprilat (50 microM), tyramine failed to increase both 2,3- and 2,5-dihydroxylation. Therefore, the effects of imidaprilat on the *OH generation in the sympathetic nerve blockaded hearts by reserpine treatment were not observed. Moreover, to examine the effect of imidaprilat on *OH formation by ischemia/reperfusion of the myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery. When the heart was reperfused, elevation of NE and 2,3- and 2,5-DHBA in imidaprilat (50 microM)-pretreated animals was not observed in the heart dialysate. Imidaprilat 2.5 mg/kg i.p. pretreatment at 5 h before coronary occlusion significantly blunted the rise of serum creatine phosphokinase and improved the electrocardiogram 2 h after coronary occlusion. These results suggest that imidaprilat, an ACE inhibitor, is associated with cardioprotective effect due to the suppression of NE-induced *OH generation.
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PMID:Protective effect of imidaprilat, an angiotensin-converting enzyme inhibitor on *OH generation in rat myocardium. 1057 26

We examined the effect of NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, on extracellular potassium ion concentration ([K+]o) and induced hydroxyl free radical (.OH) generation by an in vivo microdialysis technique. A flexibly mounted microdialysis technique was used to detect the generation of .OH in in-vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and tissue was perfused with Ringer's solution through the microdialysis probe at a rate of 1.0 microl/min. To measure the level of .OH, sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). Induction of high-concentration [K+]o (20, 70 and 140 mM) significantly increased formation of .OH trapped as 2,3-DHBA in a concentration-dependent manner. However, the application of L-NAME (50 mg/kg, i.v.) and allopurinol, a xanthine oxidase inhibitor, abolished the [K+]o depolarization-induced .OH generation. Tyramine (1.0 mM) increased the level of 2,3-DHBA. However, the application of L-NAME did not change the level of 2,3-DHBA. On the other hand, pretreatment with allopurinol (10 mg/kg, i.v.) abolished the KCl- or tyramine-induced .OH generation. Moreover, when iron (II) was administered to [K+]o (70 mM)-pretreated animals, there was a marked increased in the level of 2,3-DHBA. However, the application of L-NAME was not related to a Fenton-type reaction via [K+]o depolarization-induced .OH generation. To examine the effect of L-NAME on ischemic/reperfused rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion by left anterior descending coronary artery branch (LAD). When the heart was reperfused, a marked elevation of the level of 2,3-DHBA was observed. However, L-NAME attenuated .OH generation by ischemic/reperfused rat heart. These results suggest that NOS inhibition is associated with a cardioprotective effect due to the suppression of [K+]o depolarization-induced .OH generation.
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PMID:Nitric oxide induces hydroxyl radical generation in rat hearts via depolarization-induced nitric oxide synthase activation. 1148 40