Role of sympathoadrenal medullary activation in the initiation and progression of atherosclerosis.
Clinical and epidemiological investigations provide evidence that psychosocial factors influence the development of coronary heart disease and underlying atherosclerosis, an association that appears to be independent of the effects of other coronary disease risk factors. It has been hypothesized that sympathoadrenal medullary activation mediates behavioral influences on coronary disease, perhaps by potentiation of atherogenesis. This article summarizes four recent studies of the effects of psychosocial stress and sympathetic arousal on atherogenesis in cynomolgus monkeys (Macaca fascicularis) and rabbits. It is reported that socially dominant male monkeys, when fed an atherogenic diet and subjected to periodic social disruption, developed markedly worsened coronary atherosclerosis in comparison with subordinate monkeys; this effect may have been sympathetically mediated, as it was inhibited in similarly aggressive monkeys treated with a beta-adrenergic blocking agent. Studies using chow-fed rabbits demonstrated that exposure to chloralose anesthesia (an agent that provokes profound sympathetic activation) induced endothelial injury (indicated by intracellular accumulation of immunoglobulin G in the aortic endothelium) and abnormal (increased) platelet accumulation. The further observation that these effects were inhibited under beta-adrenoceptor blockade implicates sympathoadrenomedullary arousal in the initiation of atherogenesis. Additionally, sympathetically mediated endothelial damage and increased platelet accumulation occurred preferentially at circumostial sites in the rabbits, a finding consistent with the hypothesis that the hemodynamic concomitants of sympathetic activation contribute to atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Comparative Medicine, Bowman Gray School of Medicine, Winston-Salem, N.C. 27103.
J R
JR
Kaplan
K
K
Pettersson
S B
SB
Manuck
G
G
Olsson
D000313:Adrenal Medulla / Q000502:physiology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001792:Blood Platelets / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D011817:Rabbits; D013312:Stress, Physiological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000502:physiology*
D000319:Adrenergic beta-Antagonists