ACTIVATION OF ISCHEMIA-SENSITIVE AND REPERFUSION-SENSITIVE ABDOMINAL VISCERAL C-FIBER AFFERENTS - ROLE OF HYDROGEN-PEROXIDE AND HYDROXYL RADICALS

Abdominal ischemia and reperfusion evoke reflex excitation of the card iovascular system and generate reactive oxygen species. We have shown previously that the reactive oxygen species hydrogen peroxide (H2O2) e licits reflex excitation of the cardiovascular system after serosal ap plication to abdominal organs. However, it is not known if ischemia-se nsitive afferents respond to reactive oxygen species or if scavengers such as dimethylthiourea (DMTU) inhibit the response of these afferent s to ischemia or reperfusion. Therefore, to provide more information o n the neurophysiological mechanisms underlying the activation of these afferents, we studied their responses to H2O2 applied to the receptiv e field during recordings of single-unit activity of ischemia-insensit ive or -sensitive abdominal visceral C fiber afferents in anesthetized cats. Additionally, we recorded single-unit activity of ischemia and reperfusion-sensitive afferents before and after treatment with DMTU ( 10 mg/kg), which scavenges H2O2 and hydroxyl radicals or the iron chel ator deferoxamine (DEF, 10 mg/kg), which inhibits hydroxyl radical for mation. Application of 44 mumol H2O2 to afferent endings increased the discharge frequency in nine of 11 ischemia-sensitive units, from 0.01 +/-0.01 to 0.67+/-0.16 impulses per second. In contrast, only one of 1 0 ischemia-insensitive C fibers responded to H2O2 application. In an a dditional 13 ischemia-sensitive C fibers, DMTU significantly (p<0.05) attenuated ischemia-induced increases in discharge frequency from 0.42 +/-0.18 to 0.24+/-0.1 impulses per second (ischemia versus DMTU+ischem ia, respectively). In eight additional C fibers, we found that reperfu sion after 5 minutes of ischemia was associated with an increase in di scharge activity from a baseline activity of 0.02+/-0.01 to 0.44+/-0.0 7 impulses per second. DMTU significantly attenuated the reperfusion-i nduced increases in discharge frequency from 0.08+/-0.04 to 0.18+/-0.0 6 impulses per second. DEF significantly (p<0.05) attenuated the incre ased discharge activity from 0.39+/-0.07 to 0.10+/-0.04 impulses per s econd (ischemia versus DEF+ischemia, respectively) in an additional 11 ischemia-sensitive C fibers. In contrast, iron-saturated DEF did not attenuate ischemia- and reperfusion-induced increases in impulse activ ity. Thus, ischemia-sensitive but not ischemia-insensitive abdominal v isceral afferents respond to H2O2. Furthermore, ischemia- and reperfus ion-sensitive afferents decreased their impulse activity to a repeated period of ischemia or reperfusion after DMTU or DEF treatment. These data suggest that reactive oxygen species, particularly H2O2 and hydro xyl radicals, activate abdominal visceral C fibers in the cat during b rief periods of ischemia and reperfusion.