Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet.

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 < .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 ,B-adrenergic-blocking agents may confer a degree of protection against CAA among individuals behaviorally predisposed to coronary heart disease.Circulation 76, No. 6, 1364No. 6, -1372No. 6, ,1987 THERE IS increasing evidence that the behavioral attributes of individuals contribute to risk for atherosclerosis and coronary heart disease (CHD). Among human beings, the so-called type A behavior pattern (and, more specifically, the propensity to experience excessive anger or hostility) has been found to be predictive of CHD events in prospective studies of initially healthy individuals.1-7 Similarly, we have observed that when male cynomolgus monkeys fed atherogenic diets are housed in an unstable or stressful social setting, the highly aggressive and competitive dominant animals develop greater coronary artery atherosclerosis than their more submissive, subordinate counterparts

A mechanism converting psychosocial stress into mononuclear cell activation

“…Here we present an adrenergic signaling pathway that explains the rapid increase in activation of the transcription factor NF-B observed in PBMC shortly after exposure to psychosocial stress, thus linking psychosocial stress to mononuclear cell activation and subsequent changes in the immune system. This extends previous work showing a role of catecholamines in the mechanism for atherosclerosis (8)(9)(10)(11)(12). The observation that mental stress in humans and rodents results in nuclear translocation of NF-B and changes in transcriptional activity thus closes an important gap in understanding the cellular consequences of psychosocial stress.…”

“…Potential toxic elements in the personality construct such as hostility, anger, cynicism, mistrust, and unhealthy lifestyle (1,5,6), as well as social isolation (5), lack of social support (6), and work-related stress (7), increase the risk for cardiovascular disease, suggesting a strong causal relationship between chronic stress and the development of atherosclerosis (1). Intervention studies in cynomolgus monkeys support this concept, showing not only activation of these processes by mental stress but also reduction of vascular dysfunction and disease by reducing psychosocial stress through ␤-adrenergic blockade (8)(9)(10)(11)(12). Consistently, behavioral interventions, stress reduction, and stress management demonstrated benefits over and above usual medical care in hypertensive African Americans (13) and in cardiac patients with evidence of myocardial ischemia (14)(15)(16)(17)(18).…”

Transdermal oestrogen reduces daytime blood pressure in hypertensive women

“…31 Further, heart rate is known to be a marker of sympathetic activity, and the oestrogen-induced changes in the present study were present when mean heart was elevated. 32 Our data may indicate an effect of oestrogen on vasodilatation via the sympathetic system. When HR is maintained on a higher level the difference in BP is present, but during the night-time, when the sympathetic system is less activated, the effect of oestrogen will not be so large.…”

Cardiac sequelae in Brooklyn after the September 11 terrorist attacks

“…These psychosocial factors are composed of depression, anxiety, personality and character traits as well as chronic and subacute life stress. 4,[10][11][12][13] A growing number of epidemiologic studies has suggested that anger and hostility are related to incidence of MI, 14 especially in older men. 14,15 Efforts to raise public awareness of these issues may carry a larger importance as terrorism remains a constant threat.…”