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Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet
J R Kaplan1, S B Manuck, M R Adams
1Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
Abstract:
We studied the effect of propranolol on the diet-induced coronary artery atherosclerosis (CAA) in 30 adult male cynomolgus monkeys living in social groupings of five animals each. Animals in the "treated" segment (n = 15) consumed propranolol, which was mixed into an atherogenic diet. Animals in the "untreated" group (n = 15) consumed only the atherogenic diet. Finally, the social groupings were subjected to disruption through monthly redistribution of monkeys among the groups within each treatment segment. The experiment lasted 26 months, following which all animals underwent autopsy during which the coronary arteries were evaluated for atherosclerosis. Regarding atherosclerosis, we observed a significant interaction between social status and experimental condition (p less than .03). Socially dominant animals had (as in previous studies) significantly exacerbated CAA, but only in the untreated segment; the effect of social dominance on CAA was abolished by long-term administration of propranolol. The antiatherogenic effect of propranolol on dominant animals was independent of the influences of serum lipid concentrations, blood pressure, and resting heart rate. We conclude that treatment with beta-adrenergic-blocking agents may confer a degree of protection against CAA among individuals behaviorally predisposed to coronary heart disease.
Insights
Propranolol treatment abolished the exacerbation of coronary artery atherosclerosis (CAA) in socially dominant monkeys. This beta-blocker may protect individuals prone to heart disease.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Primate Research
Background:
- Social hierarchy and stress are known risk factors for atherosclerosis.
- Diet-induced coronary artery atherosclerosis (CAA) is a significant health concern.
- Beta-adrenergic-blocking agents like propranolol have potential cardiovascular benefits.
Purpose of the Study:
- To investigate the effect of propranolol on diet-induced CAA in a primate model.
- To determine if propranolol mitigates the impact of social stress on atherosclerosis development.
- To explore the antiatherogenic mechanisms of propranolol independent of traditional cardiovascular risk factors.
Main Methods:
- Thirty adult male cynomolgus monkeys were fed an atherogenic diet for 26 months.
- Fifteen monkeys received propranolol mixed with their diet; fifteen received the diet alone.
- Monthly redistribution of monkeys simulated social disruption within treatment groups.
Main Results:
- A significant interaction was observed between social status and experimental condition (p < .03).
- Socially dominant monkeys exhibited exacerbated CAA, but only in the untreated group.
- Propranolol abolished the effect of social dominance on CAA, independent of lipid levels, blood pressure, or heart rate.
Conclusions:
- Long-term propranolol administration can protect against CAA in socially dominant individuals.
- Beta-adrenergic-blocking agents may offer protection against coronary heart disease in behaviorally predisposed individuals.
- Propranolol's antiatherogenic effects in this model are not mediated by changes in serum lipids, blood pressure, or heart rate.