Hydrogen peroxide-induced cardiovascular reflexes. Role of hydroxyl radicals.
Mesenteric ischemia reflexly activates the cardiovascular system. In addition, mesenteric ischemia and reperfusion generate reactive oxygen species. However, the ability of these short-lived reactive oxygen species to generate cardiovascular reflexes is unknown. We therefore investigated cardiovascular reflexes induced by serosal application of hydrogen peroxide (H2O2) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 mumols) to the gallbladder (n = 14) significantly (p less than 0.05) increased mean arterial blood pressure (MAP) by 37 +/- 6 mm Hg, left ventricular dP/dt by 1,893 +/- 416 mm Hg/sec, heart rate by 6 +/- 1 beats per minute, and systemic vascular resistance from 0.34 +/- 0.01 to 0.42 +/- 0.04 peripheral resistance units. The cardiovascular effects were dose-dependent over a range of 0.4 pmol to 132 mumols H2O2. Celiac and superior mesenteric ganglionectomy abolished H2O2-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p less than 0.05) attenuated 44 mumols H2O2-induced increases in MAP from 36 +/- 3 to 2 +/- 2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 mumols H2O2-induced increases in MAP from 40 +/- 7 to 19 +/- 10 mm Hg, but iron-loaded deferoxamine did not. Aspirin (50 mg/kg) did not attenuate H2O2-induced excitation of the cardiovascular system. These data suggest that H2O2 activates abdominal visceral afferents to reflexly stimulate the cardiovascular system by a mechanism involving hydroxyl radicals. Thus, reactive oxygen species could modulate systemic vascular tone by stimulating abdominal visceral afferents during mesenteric ischemia and reperfusion.
Stahl
G L
GL
Department of Internal Medicine, University of California, Davis 95616.
Halliwell
B
B
Longhurst
J C
JC
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D002415:Cats; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D005609:Free Radicals; D005704:Gallbladder / Q000187:drug effects; D006439:Hemodynamics; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D008643:Mesentery / Q000098:blood supply; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D015424:Reperfusion; D013270:Stomach / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D005609:Free Radicals; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D013890:Thiourea; D003676:Deferoxamine; D001241:Aspirin