title: Central GABAA receptors are involved in inflammatory and cardiovascular consequences of endotoxemia in conscious rats.
abstract: γ-Aminobutyric acid (GABA), the principal brain inhibitory neurotransmitter, modulates inflammatory and neurodegenerative disease. Here, we tested the hypothesis that central GABAergic neurotransmission mediates the detrimental inflammatory, hemodynamic, and cardiac autonomic actions of endotoxemia. The effects of drugs that block GABA receptors or interfere with GABA uptake or degradation on blood pressure (BP), heart rate (HR), and HR variability (HRV) responses elicited by i.v. lipopolysaccharide (LPS) were assessed in conscious rats. The hypotensive effect of LPS (10 mg/kg) was blunted after intracisternal (i.c.) administration of bicuculline (GABAA receptor antagonist) or saclofen (GABAB receptor antagonist). By contrast, the concomitant LPS-evoked tachycardia and decreases in time domain and frequency domain indices of HRV (measures of cardiac autonomic control) were abolished upon treatment with bicuculline but not saclofen. Increases in serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) caused by LPS disappeared in the presence of bicuculline or saclofen, whereas LPS-evoked increases in serum nitric oxide metabolites (NOx) were counteracted by bicuculline only. None of the endotoxemia effects was altered in rats treated with i.c. tiagabine (GABA reuptake inhibitor) or vigabatrin (GABA transaminase inhibitor). These data suggest a major role for central GABAA receptors in the inflammatory and cardiovascular effects of endotoxemia.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Marwa Y
authors.initials: MY
authors.lastname: Sallam
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Sahar M
authors.initials: SM
authors.lastname: El-Gowilly
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Abdel-Galil A
authors.initials: AG
authors.lastname: Abdel-Galil
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. mahelm@hotmail.com.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D019446:Endotoxemia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D018682:GABA Agents / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology; D000078308:Tiagabine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D020888:Vigabatrin / Q000494:pharmacology
chemical_list: D018682:GABA Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020888:Vigabatrin; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline; D000078308:Tiagabine
keywords: Cardiac autonomic control; Cisterna magna; Endotoxemia; GABA receptors; Heart rate variability; Hypotension