Understanding mechanisms leading to essential hypertension has been challenging even after several decades of research. Long-term regulation of arterial pressure is generally linked to the ability of the kidneys to maintain volume homeostasis by altering the renal excretion of salt and water in response to changes in arterial pressure. But there is also compelling evidence for a role of the central nervous system in long-term regulation of arterial pressure, primarily by modulating sympathetic nerve activity. Sympathetic nervous system activation contributes to the pathogenesis of human hypertension. Recent evidence points to mineralocorticoids as a cause of sympathetic overactivity in hypertension. In the studies for this dissertation, low dose deoxycorticosterone acetate along with high salt in drinking water with both kidneys intact was used as a model (mild DOCA-salt hypertension model) to understand the role of the sympathetic nervous system in hypertension caused by mineralocorticoids. My studies indicate hypertension development is not associated with global increases in sympathetic activity. Contrary to the classical thought about importance of renal nerves, I found that renal nerves are not essential for hypertension development. In fact, my studies indicate that regional sympathetic activity specifically to splanchnic vascular bed is required for full development of hypertension. I concluded that sympathetically mediated vasoconstrictor effects to the splanchnic organs are likely enhanced in mineralocorticoid hypertension due to increased responsiveness of the splanchnic blood vessels to norepinephrine. The data in this dissertation suggest that splanchnic sympathetic activity and splanchnic vascular reactivity are important in regulation of blood pressure in mineralocorticoid-salt induced hypertension.
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