Prazosin attenuates hydroxyl radical generation in the rat myocardium.
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.
Obata
T
T
Department of Pharmacology, Oita Medical University, Hasama-machi, Japan. tobata@oita-med.ac.jp
Yamanaka
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020156:Salicylic Acid / Q000378:metabolism; D014439:Tyramine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D007501:Iron; D020156:Salicylic Acid; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin