Sympathoinhibition and its reversal by naloxone during hemorrhage.
During hemorrhagic hypotension, vascular resistance, plasma norepinephrine, and sympathetic nerve activity decrease. Naloxone reverses these effects. We hypothesized that increased sympathetic nerve activity was specific to naloxone and not secondary to the pressor response. Conscious rabbits were hemorrhaged until mean arterial pressure (MAP) was less than 40 mmHg, given naloxone (3 mg/kg) or saline, and monitored for 5 min. In some animals, we attenuated naloxone's pressor response with alpha-adrenergic blockade or mimicked the pressor response by infusion of phenylephrine. During nonhypotensive hemorrhage, heart rate and renal sympathetic nerve activity (RSNA) increased significantly. During hypotensive hemorrhage, RSNA decreased to significantly less than prehemorrhage control values. After saline treatment, RSNA did not increase. Naloxone significantly increased MAP and RSNA. alpha-Blockade reduced the pressor response to naloxone but not the increase in RSNA. Phenylephrine increased MAP to a level similar to naloxone, but RSNA remained suppressed. Reinfusion of hemorrhaged blood reduced RSNA in all groups treated with naloxone. These data suggest that hypotensive hemorrhage is associated with sympathoinhibition that is not transient. In addition, the pressor response to naloxone is not required for its sympathoexcitatory effects.
Hasser
E M
EM
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Schadt
J C
JC
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013997:Time Factors
D010656:Phenylephrine; D009270:Naloxone; D011224:Prazosin; D010646:Phentolamine