Cardiovascular effects of beta-carbolines in conscious rats.
The beta-carbolines have a high affinity for the benzodiazepine receptor, where they demonstrate actions opposite to those of the benzodiazepines and elicit anxiogenic effects. We tested the acute cardiovascular effects of beta-carbolines in conscious unrestrained rats. Intravenous infusion of ethyl-beta-carboline-3-carboxylate (BCCE) or methyl-beta-carboline-3-carboxylate (BCCM) caused dose-related decreases in heart rate. Pretreatment with RO 15-1788 (10.0 mg/kg, i.v.), a benzodiazepine receptor antagonist, or atropine (1.0 mg/kg, i.v.) prevented the bradycardia elicited by BCCE (3.0 mg/kg, i.v.). In contrast, tetrahydro-beta-carboline (THBC; 3.0 mg/kg, i.v.) increased both heart rate and blood pressure significantly as compared with controls. However, larger doses of THBC failed to elicit further increases in heart rate or blood pressure. These experiments indicate that in conscious unrestrained rats, beta-carbolines given acutely do not routinely elicit the cardiovascular changes normally associated with stress or anxiety. We next extended our observations to rats given the beta-carboline noreleagnine, 2 mg/kg, or vehicle twice daily intraperitoneally for 4 weeks. The rats were fed either a high salt (8%) or a low salt (0.9%) diet. At 4 weeks, rats given noreleagnine and high salt had higher tail cuff pressures (146 +/- 4 vs. 134 +/- 4 mmHg) than those given noreleagnine and low salt. However, with direct arterial measurement, these differences disappeared. These data suggest that beta-carbolines do not provide a useful model for investigating the effects of chronic stress on cardiovascular function in rats.
Department of Pharmacology, Indiana University School of Medicine, Indianapolis, USA.
J H
JH
Wible
F C
FC
Luft
D
D
Stock
J A
JA
DiMicco
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002243:Carbolines / Q000008:administration & dosage*; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D058785:GABA-A Receptor Agonists; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000139:chemically induced*
D002243:Carbolines; D058785:GABA-A Receptor Agonists