Central cardiovascular effects of CPU-23, a substituted tetrahydroisoquinoline, in rats.
The cardiovascular effects of intracerebroventricular (i.c.v.) injections of low doses of CPU-23, a substituted tetrahydroisoquinoline, were investigated and compared with those of nifedipine in pentobarbital-anaesthetized Sprague-Dawley rats. CPU-23, in doses of 0.2 to 0.5 mg/kg (i.c.v.), which did not elicit any significant cardiovascular responses when injected intravenously, caused a clear-cut and long-lasting decrease of mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner. The effects of CPU-23, in a dose of 0.05 mg/kg, were similar to those of nifedipine, a prototype L-type calcium antagonist. The hypotensive effects of CPU-23 were significantly attenuated by bilateral cervical vagotomy. The results strongly suggest that a central component may be involved in the cardiovascular effects of CPU-23 and that dihydropyridine receptor sites in the brain may be involved in the central control of cardiovascular functions.
Department of Biophysics, School of Basic Medical Sciences, Shanghai Medical University, P.R.C.
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Lee
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Wong
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020746:Calcium Channels, L-Type; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines; D014628:Vagotomy
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002317:Cardiovascular Agents; D007546:Isoquinolines; D010880:Piperidines; D011950:Receptors, Cholinergic; D044005:Tetrahydroisoquinolines; C077683:CPU 23; D009543:Nifedipine