title: Platelet and brain alpha 2-adrenoceptors and cardiovascular sensitivity to agonists in dogs suffering from endotoxic shock.
abstract: We examined the changes in alpha 2-adrenoceptor binding on platelet and brain membranes of dogs treated with a non-lethal dose of endotoxin (0.1 mg/kg intravenously), and the alpha 2-adrenoceptor mediated cardiovascular effects during endotoxin shock. At 2 h, 24 h, and 7 days after endotoxin administration, the number of binding sites (Bmax) of [3H]yohimbine binding decreased and equilibrium dissociation constants (Kd) increased in platelets, whereas both Bmax and Kd decreased in either cerebral cortex or medulla oblongata. After 30 days of endotoxin administration, there were no significant differences in Bmax or Kd between the treated and untreated animals in both platelets and brain tissues. Significant positive correlations were observed for Bmax values between platelets and brain tissues, although negative correlations for Kd values between platelets and brain were not significant. Significant negative correlations were also observed between plasma catecholamine concentrations and platelet alpha 2-adrenoceptor number, and between plasma noradrenaline and medulla alpha 2-adrenoceptor number. Pretreatment with E coli endotoxin diminished cardiovascular effects such as bradycardia, hypotension, and increase in systemic vascular resistance induced by either i.v. clonidine or xylazine. This suggests that alpha 2-adrenoceptor activity is impaired in the central nervous system as well as in the peripheral vascular system during endotoxin shock. Therefore, platelets may in part represent a good model which reflects the alpha 2-adrenoceptor changes in the central nervous system and peripheral vascular system during and after endotoxin shock.
authors.affiliation: Department of Veterinary Internal Medicine, Faculty of Agriculture, Tottori University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hikasa
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Ogasawara
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014991:Xylazine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D004731:Endotoxins; D018341:Receptors, Adrenergic, alpha-2; D014991:Xylazine; D015016:Yohimbine; D003000:Clonidine