title: Renal sympathetic nerve activity and vascular reactivity to phenylephrine after lipopolysaccharide administration in conscious rats.
abstract: It has been proposed that sympathoexcitation is responsible for vascular desensitization toα1-adrenoceptor stimulation during lipopolysaccharide (LPS)-induced systemic inflammation. The present study tested this hypothesis by examining the effects of sympatho-deactivation with theα2-adrenoceptor agonist, dexmedetomidine, on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and vascular reactivity to phenylephrine in conscious rats with cardiac autonomic blockade (methylatropine and atenolol) following LPS administration. In male, adult Sprague-Dawley rats (n=5 per group), RSNA and MAP were continuously recorded over 1-h periods, before and after LPS administration (20 mg/kg iv), and finally after infusion of either saline or dexmedetomidine (5μg/kg, then 5μg/kg/h iv). A full dose-response curve to phenylephrine was constructed under each condition. After pooling data from both groups of rats (n=10), LPS significantly (P=0.005) decreased MAP (from 115 ± 1 to 107 ± 2 mmHg), increased RSNA (to 403 ± 46% of baseline values) and induced 4 to 5-fold increases in the half-maximal effective dose (ED50) of phenylephrine (from 1.02 ± 0.09 to 4.76 ± 0.51μg/kg). During saline infusion, RSNA progressively decreased while vascular reactivity did not improve. Treatment with dexmedetomidine decreased MAP, returned RSNA to near pre-endotoxemic levels, but only partially restored vascular reactivity to phenylephrine (ED50was still threefold increased as compared with baseline values). These findings indicate that only part of the decrease in vascular reactivity toα1-adrenoceptor stimulation during endotoxemia can be accounted for by sympathetic activation, at least on a short-term basis.
authors.affiliation: EA 7426: Pathophysiology of Injury-Induced Immunosuppression (PI), Faculty of Pharmacy, University Claude Bernard Lyon 1, Lyon, France julien@univ-lyon1.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Julien
authors.affiliation: Technical platform ANIPHY, CNRS UMS 3453 University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Oréa
authors.affiliation: Department of Physiology, University Claude Bernard Lyon 1, Lyon, France.|Anesthesiology/Critical Care, Hôpital d'Instruction des Armées Desgenettes, Lyon, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Quintin
authors.affiliation: Department of Anesthesiology and Intensive Care, Lyon-Sud Hospital, Hospices Civils de Lyon, Lyon, France.|University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Piriou
authors.affiliation: EA 7426: Pathophysiology of Injury-Induced Immunosuppression (PI), Faculty of Pharmacy, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Barrès
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007668:Kidney / Q000294:innervation*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D008070:Lipopolysaccharides; D010656:Phenylephrine
keywords: 
  LPS
  ; Dexmedetomidine; endotoxemia; sepsis; α2‐adrenoceptor agonist