Cardiovascular effects of central choline during endotoxin shock in the rat.
The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. Mecamylamine (50 microg; i.c.v.) pretreatment prevented the pressor and bradycardic responses to choline, whereas atropine (10 microg; i.c.v.) failed to alter both responses. Atropine pretreatment, alone, inhibited endotoxin-induced hypotension. The pressor responses to choline in endotoxin-treated rats were attenuated by pretreatment with hemicholinium-3 (20 microg; i.c.v.), a high-affinity neuronal choline-uptake inhibitor. Plasma vasopressin levels of endotoxin-treated rats were severalfold higher than those of control animals, and choline (50-150 microg; i.c.v.) produced further increases in plasma vasopressin in this condition. Mecamylamine abolished vasopressin response to endotoxin as well as to choline. The vasopressin receptor antagonist, (beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1)-O-Me-Tyr2,Arg8 )-vasopressin (10 microg/kg; i.v.) administered 5 min after choline decreased blood pressure from the increased level to the precholine levels but did not alter bradycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presynaptic mechanism leading to the activation of central nicotinic cholinergic pathways. An increase in plasma vasopressin levels seems to be involved in the pressor, but not in the bradycardic response, to choline.
Savci
V
V
Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey.
Ulus
I H
IH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002794:Choline / Q000008:administration & dosage / Q000627:therapeutic use*; D018678:Cholinergic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D006339:Heart Rate / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy; D014667:Vasopressins / Q000097:blood
D018678:Cholinergic Agents; D004731:Endotoxins; D006727:Hormone Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D014667:Vasopressins; D002794:Choline