PSYCHOSOCIAL STRESS CAUSES ENDOTHELIAL INJURY IN CYNOMOLGUS MONKEYS VIA BETA-1-ADRENOCEPTOR ACTIVATION

Current evidence links psychosocial factors to exacerbation of diet-in duced atherosclerosis in monkeys via activation of the sympathetic ner vous system. However, it is uncertain whether these factors can potent iate initial lesion formation, and do so even in the absence of dietar y provocation, and whether any such effects can be prevented by beta-a drenergic blockade. As endothelial injury has been considered an initi ating event in atherogenesis, we studied the effect of psychosocial st ress on endothelial integrity in 48 adult male cynomolgus monkeys (Mac aca fascicularis). All animals were housed in 12 social groups of four monkeys each for 11 weeks. The monkeys in half of the groups were exp osed to a socially unstable ('stressed') condition for 72 h and receiv ed saline (n = 8), a lipophilic beta(1)-blocker (metoprolol, 0.30 mg/k g per h; n = 8), or hydrophillic beta(1)-blocker (atenolol, 0.15 mg/kg per h; n = 8). The remaining six social groups were assigned to the s ocially stable (non-stressed) condition; for 72 h these animals all re mained in their social groups and were similarly treated with saline ( n = 8), metoprolol (n = 8), or atenolol (n = 8). The frequency of IgG- positive (injured) endothelial cells was estimated on en face (Hautche n) preparations from the thoracic aorta and coronary arteries. Psychos ocial stress caused a significant increase in the number of injured en dothelial cells in the circumostial areas of the descending thoracic a orta in the placebo group (0.3 vs. 0.8%, P < 0.02), an effect that had not been demonstrated previously. Moreover, beta-blockade significant ly (P < 0.01) inhibited the stress effect, with no differences between the two beta-blocking agents. The number of injured endothelial cells in the non-branched portions of the aorta and coronary arteries were low and indistinguishable among groups; irregularities in the size and location of branching points in the coronary arteries precluded analy sis of these sites. This study demonstrated that psychosocial stress i nduces endothelial injury, and that this effect is mediated via beta(1 )-adrenoceptor activation. (C) 1998 Elsevier Science Ireland Ltd.