Prazosin attenuates hydroxyl radical generation in the rat myocardium

Abstract

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/μl/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 μM), 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 ( R 2=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 μM), 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 α 1-adrenoceptor antagonistic action of prazosin.