IDENTIFICATION OF A CORTICAL SITE FOR STRESS-INDUCED CARDIOVASCULAR DYSFUNCTION

The evidence indicating that the insular cortex is a likely candidate to mediate stress-induced cardiovascular responses is reviewed. Both neuroanatomical and electrophysiological investigations demonstrate that the insular cortex receives an organized representation of visceral information. In addition, the insular cortex also receives highly processed association cortex information. The insular cortex is also highly interconnected with many subcortical limbic and autonomic regions. This combination of sensory input and limbic/autonomic connectivity would be necessary to permit the insular cortex to be a critical site for the integration of emotional and autonomic responses. Stimulation of the insular cortex elicits specific cardiovascular and autonomic responses from discrete sites. Phasic stimulation entrained to the cardiac cycle is even capable of causing severe arrhythmias. The efferent pathways and some of the neurotransmitter mechanisms have determined. It appears that the lateral hypothalamic area is the primary site of synapse for autonomic responses originating in the insular cortex and this information is relayed by NMDA glutamatergic receptors and modulated by neuropeptides including neuropeptide Y, neurotensin, leu-enkephalin and dynorphin. Finally, a rat stroke model, which includes the insular cortex in the infarct region indicates that disruption of the insula can produce substantial cardiac and autonomic abnormalities, which might be similar to those produced by stress. Some of the chronic neurochemical changes, including increases in opioids, neuropeptide Y and neurotensin in the central nucleus of the amygdala, which might be mediating these cardiovascular disturbances, have been determined.