Sympathetic activation and tachycardia in lipopolysaccharide treated rats are temporally correlated and unrelated to the baroreflex.
The goal of this study was to investigate the sustained sympatho-excitation which occurs in sepsis and which accompanies the fall in blood pressure and to analyze its time-correlation with heart rate and the role of the baro-chemoreflexes. Rats anesthetized with pentobarbital were treated with lipolysaccharide (LPS) 20 mg/kg/20 min i.v. and mean blood pressure (MBP), heart rate (HR), rectal temperature and renal sympathetic nerve activity (RSNA) were recorded. LPS induced a fall in blood pressure, an increase in HR (+20%) and RSNA (+355%); the arterial PO2 and PCO2 remained stable and the injection was fatal within 4 h. Baroreceptor and chemoreceptor denervation accelerated the fall in MBP but did not change the survival time. Under those conditions; RSNA excitation was slightly more pronounced. During treatment with gallamine and under artificial respiration to avoid possible respiratory changes through the chemoreflex pathway, the effects of LPS remained, except for a decrease in arterial PO2. Electrolytic lesioning of the nucleus tractus solitarius or blocking the effects of baroreflex efferents by either an alpha1 or alpha2-adrenoceptor antagonists failed to alter the effects of LPS. After treatment with a beta-adrenoceptor antagonist, LPS increased RSNA but not HR and the survival time of the rats shortened. LPS administered i.c. (1 mg/kg) induced, with a short latency, effects comparable to those produced by i.v. injection. Surprisingly, the time correlation between RSNA and HR rhythms persisted when MBP dropped after LPS and moreover it reappeared in baroreceptor denervated rats after LPS. Thus under these conditions of altered baroreflex pathway and LPS induced sympathetic activation, the sympathetic output from the medulla appears to play a role in the correlation between heart rate and sympathetic nerve activity. These data indicate that the marked RSNA activation and the tachycardia are correlated and that the baroreflex and chemoreflex are not inhibited during sepsis but appear to be of minor importance in the sympathetic activation and in the blood pressure modifications.
Division of Angiology, Servier Research Institute, 11 rue des Moulineaux, 92150 Suresnes, France.
Christine
C
Vayssettes-Courchay
Françoise
F
Bouysset
Tony J
TJ
Verbeuren
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003714:Denervation; D004347:Drug Interactions; D019446:Endotoxemia / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D019329:Idazoxan / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013610:Tachycardia / Q000503:physiopathology*
D000317:Adrenergic alpha-Antagonists; D008070:Lipopolysaccharides; D011224:Prazosin; D019329:Idazoxan