The cardiovascular and autonomic effects of repeated administration of delta-9-tetrahydrocannabinol to rhesus monkeys. 1981

A B Fredericks, and N L Benowitz, and C Y Savanapridi

The cardiovascular effects of repeated dosing with delta-9-tetrahydrocannabinol (THC) were examined in chronically catheterized, conscious rhesus monkeys. THC (0.5 mg/kg) was administered i.v. every 6 hr for 3 weeks. Following the first THC bolus, a tachycardia (peak change, 34 beats/min) and hypotension (peak change, -21 mm Hg systolic blood pressure) sometimes preceded by a transient blood pressure increase were observed. Tolerance developed to the tachycardia and systolic blood pressure increase but not to the blood pressure decrease. Hourly measurement of systolic blood pressure and heart rate during the intervals between injections revealed heart rate decreases to which tolerance developed and blood pressure decreases which were sustained throughout the course of TCH dosing. Urinary catecholamine excretion increased during the 1st week of dosing and subsequently returned toward base-line levels. Control of basal heart rate and reflex heart rate changes was examined using autonomic agonists and antagonists. Heart rate decreases after beta adrenergic blockage (sotalol HCl) were attenuated, whereas heart rate increases after cholinergic blockade (atropine methylnitrate increases after cholinergic blockade (atropine methylnitrate) were augmented. Baroreceptor gain, measured as the ratio of heart rate change to systolic blood pressure change in response to phenylephrine, increased. The response of basal heart rate to antagonists and the augmented reflex bradycardia suggest that THC alters autonomic control of the cardiovascular system resulting in parasympathetic dominance. Divergent patterns of development of tolerance to heart rate and blood pressure effects suggest that THC affects heart rate and blood pressure through different mechanisms.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D008297 Male Males
D010656 Phenylephrine An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. (R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol,Metaoxedrin,Metasympatol,Mezaton,Neo-Synephrine,Neosynephrine,Phenylephrine Hydrochloride,Phenylephrine Tannate,Neo Synephrine,Tannate, Phenylephrine
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
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
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
D001341 Autonomic Nervous System The ENTERIC NERVOUS SYSTEM; PARASYMPATHETIC NERVOUS SYSTEM; and SYMPATHETIC NERVOUS SYSTEM taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the CENTRAL NERVOUS SYSTEM, especially the HYPOTHALAMUS and the SOLITARY NUCLEUS, which receive information relayed from VISCERAL AFFERENTS. Vegetative Nervous System,Visceral Nervous System,Autonomic Nervous Systems,Nervous System, Autonomic,Nervous System, Vegetative,Nervous System, Visceral,Nervous Systems, Autonomic,Nervous Systems, Vegetative,Nervous Systems, Visceral,System, Autonomic Nervous,System, Vegetative Nervous,System, Visceral Nervous,Systems, Autonomic Nervous,Systems, Vegetative Nervous,Systems, Visceral Nervous,Vegetative Nervous Systems,Visceral Nervous Systems

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