CARDIOVASCULAR EFFECTS OF CENTRAL CHOLINE DURING ENDOTOXIN-SHOCK IN THE RAT

The cardiovascular effects of intracerebroventricular (i.c.v.) adminis tration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachyca rdia within 10 min of treatment. Choline (50, 100, and 150 mu g; i.c.v .) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. Mecamylamine (50 mu g; i.c.v.) pre treatm ent prevented the presser and bradycardic responses to choline, wherea s atropine (10 mu g; i.c.v.) failed to alter both responses. Atropine pretreatment, alone, inhibited endotoxin-induced hypotension. The pres ser responses to choline in endotoxin-treated rats were attenuated by pretreatment with hemicholinium-3 (20 mu g; i.c.v.), a high-affinity n euronal choline-uptake inhibitor. Plasma vasopressin levels of endotox in-treated rats were severalfold higher than those of control animals, and choline (50-150 mu g; i.c.v.) produced further increases in plasm a vasopressin in this condition. Mecamylamine abolished vasopressin re sponse to endotoxin as well as to choline. The vasopressin receptor an tagonist, ylene-propionyl(1)-O-Me-Tyr(2),Arg(8))-vasopressin (10 mu g/ kg; i.v.) administered 5 min after choline decreased blood pressure fr om the increased level to the precholine levels but did not alter brad ycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presyna ptic mechanism leading to the activation of central nicotinic choliner gic pathways. An increase in plasma vasopressin levels seems to be inv olved in the presser, but not in the bradycardic response, to choline.