Hydrogen peroxide-induced cardiovascular reflexes. Role of hydroxyl radicals

G L Stahl, B Halliwell, J C Longhurst
1992 Circulation Research  
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 (H202) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 gmol) to the
more » ... dder (n=14) significantly (p<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 ,umol H202. Celiac and superior mesenteric ganglionectomy abolished H202-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p<0.05) attenuated 44 gmol H202-induced increases in MAP from 36±3 to 2±2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 pmol H202-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 H202-induced excitation of the cardiovascular system. These data suggest that H202 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. (Circulation Research 1992;71:295-302) A ctivation of mechanosensitive and chemosensitive afferents within the abdominal viscera (i.e., gallbladder, stomach, pancreas, and duodenum) induces cardiovascular reflexes.12 They are predominantly mediated by AS and C fibers that travel with the splanchnic nerve. These reflexes include increased heart rate, blood pressure, myocardial contractility, and total peripheral resistance. Mesenteric artery occlusion in cats, resulting in ischemia, evokes reflex excitation of the cardiovascular system,3,4 but the mechanisms underlying this effect are poorly understood. Various metabolites produced during ischemia, including bradykinin,1"5-8 lactic acid,9 and prostaglandins,6"10 have been reported to elicit cardiovascular reflexes and to stimulate abdominal sensory endings in the cat. Periods of visceral ischemia followed by reperfusion are well known to generate free radicals and other From the Divisions of Cardiovascular (G.L.S., J.C.L.) and Pulmonary/Critical Care (B.H.) Medicine, reactive oxygen species.5"1"12 The major reactive oxygen species are superoxide radical (02'-), hydrogen peroxide by guest on
doi:10.1161/01.res.71.2.295 pmid:1628388 fatcat:j3sum6m465fi3dr57oezyitaqy