Coronary artery spasm in the rat induced by hypothalamic stimulation.

Anesthetized rats were sterotaxically implanted with electrodes and electrically stimulated in the lateral hypothalamus. During elevation of the S-T segment on simultaneous precordial electrocardiograms, the heart was perfused with glutaraldehyde-paraformaldehyde fixative and the major coronary arteries prepared for morphometry of luminal dimensions. A similar procedure was performed in a second group receiving intravenous arginine vasopressin (AVP) in place of hypothalamic stimulation. Elevation of the S-T segment was present in these animals as well. Control animals were implanted, not stimulated and otherwise treated in the same way. Morphometry showed that reductions of mean luminal diameter and cross-sectional area of statistical significance occurred in the two experimental groups compared to controls, suggesting that coronary spasm was the cause of the elevated S-T segments. Pooled plasma from separate groups of implanted control and hypothalamically-stimulated animals revealed substantial elevation of AVP levels in the latter raising the possibility that the neuroendocrine was involved in eliciting coronary artery spasm.

Endothelial morphology and plasma total and high density lipoprotein cholesterol changes in hypothalamically stimulated squirrel monkeys fed a modified atherogenic diet.

Experimental animals fed atherogenic diets show endothelial damage, impairment of endothelial regeneration and plasma lipid changes characterized by elevation of LDL and decrease of HDL cholesterol concentrations. Previous studies in this laboratory disclosed that chronic electrical stimulation of the lateral hypothalamus was associated with electron-microscopic evidence of endothelial injury in rats and squirrel monkeys maintained on basal (low fat/cholesterol-free) diets. In the present investigation squirrel monkeys fed similar diets supplemented with "modest" amounts of caloric fat and cholesterol were subjected to chronic lateral hypothalamic stimulation for periods as long as 20 months with the expectation that endothelial injury would be greater than in the absence of the supplements. The expectations were not substantiated. Endothelium was found to be surprisingly intact by electron microscopy and similar to that of implanted nonstimulated controls. A further observation of interest was the cholesterolemic response, notably in the HDL fraction, observed in both groups, but more striking in experimental animals. The data suggest that an interaction between a modified lipid/cholesterol diet and hypothalamic stimulation may lead to elevation of plasma HDL cholesterol concentration and preservation of endothelial integrity. Further investigation is required to determine whether these two events are causally related.

Effect of hypothalamic stimulation on the endothelial morphology of the aorta in the conscious squirrel monkey.

The role of neurogenic factors in the development of atherosclerosis has not previously been studied in detail. In recent years evidence has accumulated to implicate endothelial injury as a primary stimulus for the proliferation of myo-intimal cells resulting in the formation of the early morphologic lesion. In the present investigation, the effect on aortic endothelial morphology of repetitive electrical stimulation of the lateral hypothalamus in the conscious, unrestrained squirrel monkey, maintained on a cholesterol-free low-fat diet, has been studied. Stimulation was performed with a self-powered, miniaturized electronic stimulator connected to indwelling electrodes. Implanted nonstimulated animals served as controls. Endothelial injury in the form of cell degeneration, denudation, with plasma insudation and partial junctional separation were observed electron-microscopically in stimulated animals compared with controls. These alterations were found to be independent of hypercholesterolemia and/or hypertension. Possible pathways for the induction of injury in this neurogenic model are: (1) direct, through neural circuits from the brain to the vessel wall, and (2) indirect, by elaboration of angiopathic substances inside or outside of the CNS, released into the circulation and transported to the vessel wall where they exert their effects. Reversibility of the endothelial injury progression to established lesions and mechanisms involved remain to be determined in further investigations.