Cardiovascular effects of the beta-carboline FG 7142 in borderline hypertensive rats. 1998

R P Soltis, and V L McGee, and M R Smith
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Drake University, Des Moines, Iowa 50311, USA. bob.soltis@drake.edu

The hypothesis that acute and chronic administration of the benzodiazepine inverse agonist FG 7142 (N-methyl-beta-carboline-3-carboxamide) produces cardiovascular changes similar to those seen during acute and chronic episodes of stress was studied using conscious, unrestrained borderline hypertensive rats (BHR). Chronic intraperitoneal administration of FG 7142 (10 mg/kg; 5 days/week for 8 weeks) failed to alter resting mean arterial pressure or heart rate compared to maturation and vehicle controls. However, chronic administration of FG 7142 prevented the hypertension associated with a high salt diet. Similarly, acute intravenous (i.v.) administration of FG 7142 (10 mg/kg) in BHR rendered hypertensive with a high-salt diet produced a significant reduction in resting mean arterial pressure as well as marked increases in heart rate. Pretreatment with the benzodiazepine receptor antagonist flumazenil (RO 15-1788, 10 mg/kg, i.v.) blocked the tachycardic response but had no effect on the hypotensive effect of FG 7142 administered i.v. in BHR with salt-induced hypertension. Acute administration of FG 7142 (0.1-10 mg/kg, i.v.) in normal BHR produced no significant changes in resting mean arterial pressure and dose-related increases in heart rate. These experiments indicate that, in conscious unrestrained BHR, FG 7142 can elicit changes in heart rate but not the changes in arterial pressure typically associated with stress or anxiety. Therefore, it appears that FG 7142 is of limited use as a pharmacological tool for investigating the cardiovascular effects of acute or chronic stress in BHR.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002243 Carbolines A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles. Carboline,Pyrido(4,3-b)Indole,Beta-Carbolines,Pyrido(4,3-b)Indoles,Beta Carbolines
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012982 Sodium, Dietary Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate. Dietary Sodium

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