Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Blood Pressure / drug effects*
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Calcium Channel Blockers / administration & dosage
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Calcium Channel Blockers / pharmacology
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Calcium Channel Blockers / therapeutic use
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Calcium Channels / drug effects
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Calcium Channels / metabolism
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Calcium Channels, L-Type
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Cardiovascular Agents / administration & dosage
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Cardiovascular Agents / pharmacology*
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Cardiovascular Agents / therapeutic use
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Dose-Response Relationship, Drug
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Heart Rate / drug effects*
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Injections, Intraventricular
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Isoquinolines / administration & dosage
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Isoquinolines / pharmacology*
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Isoquinolines / therapeutic use
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Male
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Nifedipine / administration & dosage
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Nifedipine / pharmacology
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Nifedipine / therapeutic use
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Piperidines / administration & dosage
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Piperidines / pharmacology*
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Piperidines / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Receptors, Cholinergic / drug effects
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Structure-Activity Relationship
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Tetrahydroisoquinolines*
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Vagotomy
Substances
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Calcium Channel Blockers
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Calcium Channels
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Calcium Channels, L-Type
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Cardiovascular Agents
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Isoquinolines
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Piperidines
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Receptors, Cholinergic
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Tetrahydroisoquinolines
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CPU 23
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Nifedipine