Spinal regulation of sympathetic nerve activity and arterial pressure under conditions of increased plasma osmolality

Abstract

Hypertension, or chronic high blood pressure, is a major health concern worldwide. Increased dietary salt may contribute to high blood pressure through the activation of the sympathetic nervous system. Indeed, more than half of the cases of human hypertension show evidence of elevated sympathetic nerve activity. Key brain regions that activate sympathetic activity in response to increased osmolality have been identified, but regulation at the level of the spinal cord - the final point of sympathetic outflow from the central nervous system - is much less understood. The experiments in this thesis were designed to examine the spinal neurotransmitters and sympathetic nerves that may increase arterial pressure in response to elevated plasma osmolality. The first major finding of this thesis suggests that the arterial pressure response to increased osmolality relies on spinal glutamate, not vasopressin as previously hypothesized. The second major finding suggests that elevated arterial pressure during water deprivation - a condition of chronic hyperosmolality - is sympathetically mediated and may be dependent on the adrenal cortex, but is not due to increased sympathetic activity to a specific vascular bed. The discoveries described in this thesis contribute to the overall knowledge of spinal regulation of osmotically driven sympathoexcitation and suggest new areas of focus for future studies. Moreover, these findings may lead to a better understanding of the etiology of salt-sensitive hypertension and development of novel antihypertensive therapies.