Circulation Research, Vol 68, 1270-1279, Copyright © 1991 by American Heart Association

ARTICLES

Endothelial dysfunction in response to psychosocial stress in monkeys

WB Strawn, G Bondjers, JR Kaplan, SB Manuck, DC Schwenke, GK Hansson, CA Shively and TB Clarkson
Arteriosclerosis Research Center, Bowman Gray School of Medicine, Winston-Salem, N.C.

The current study was designed to evaluate the effects of a disrupted social environment on the endothelial integrity of various vascular segments in male cynomolgus monkeys (Macaca fascicularis). Each of 20 single-caged adult monkeys was fed a diet comparable to a person's ingestion of 240 mg cholesterol/day for a 10-week baseline period and then was introduced as a stranger into a four-member social group for 3 days. Half of the monkeys received a beta-adrenergic blocking agent (metoprolol) via subcutaneous implant 2 days before and during group housing. The social manipulation produced persistent sympathetic arousal as evidenced by significantly elevated heart rates among untreated monkeys (p less than 0.01) but not among their metoprolol- treated counterparts, whose heart rate declined (p less than 0.05). After the social manipulation, all monkeys were necropsied and evaluated for endothelial incorporation of immunoglobulin G (as an indicator of cell death), endothelial cell replication, the presence of adherent leukocytes, and arterial low density lipoprotein permeability and concentration. At branching sites in the thoracic aorta, immunoglobulin G incorporation and endothelial cell replication were significantly greater in untreated monkeys than in metoprolol-treated monkeys (p less than 0.01 for both analyses); no differences existed at nonbranch sites. Endothelial cell replication in the coronary arteries (where immunoglobulin G incorporation was not examined) was also greater among untreated than among metoprolol-treated monkeys. No significant differences were observed between treatment groups in arterial low density lipoprotein permeability or leukocyte adherence; estimates of arterial low density lipoprotein concentrations were higher among untreated than among metoprolol-treated monkeys, but only in the abdominal portion of the aorta. These results indicate that social disruption is associated with both sympathetic nervous system arousal and indexes of endothelial dysfunction, effects that may be prevented by treatment with a beta-adrenergic blocking agent.

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