Neural control of the splanchnic circulation in AngII-salt hypertension

Abstract

Sympathetic nervous system (SNS) activity is elevated in some forms of essential hypertension. What causes sympathetic tone to be elevated, and how it mediates hypertension, however, is unclear. Angiotensin II (AngII) and a high dietary salt appears to be involved since in rats, chronic peripheral infusion of AngII induces a form of hypertension that is accompanied by increased indices of peripheral sympathetic tone selectively when they are fed a high sodium diet. Studies in this model have shown that contrary to prevailing views, peripheral sympathetic tone was diminished to the kidneys, but instead, suggested that it may be elevated selectively to the splanchnic vascular bed. Based on these findings, the initial aim of this thesis was to characterize, in conscious rats, the local hemodynamics within the splanchnic vascular bed and the role of the SNS in mediating changes in splanchnic vascular hemodynamics during AngII-salt hypertension. Studies were carried out to test the hypothesis that in addition to sympathetically mediated increases in splanchnic venous tone, AngII-salt hypertension was mediated by enhanced sympathetic vasoconstriction of splanchnic arterioles occurring through its peripheral sympathetic nerve supply. Splanchnic vascular resistance was found to be elevated in AngII-salt hypertensive rats; however, these hemodynamic changes occurred even after removal of direct sympathetic innervation to the splanchnic vascular bed by surgical denervation (celiac ganglionectomy). Furthermore, unlike previously shown, celiac ganglionectomy did not result in lowering of blood pressure during AngII-salt hypertension. Thus, contrary to the original hypothesis, changes in direct sympathetic input to the splanchnic vasculature did not mediate AngII-salt hypertension. Additional studies in this thesis found that part of the problem with this inconsistent finding may be related to the technique commonly used to generate the model. Furthermore, studies in this thesis found, using chronic pharmacological adrenergic blockade, that the contribution of the SNS in AngII-salt hypertension may have been overestimated. Thus, the combined findings in this thesis and prior studies suggest that a fraction of AngII-salt hypertension is mediated by enhanced peripheral sympathetic tone, not through direct vasoconstrictive input to the splanchnic vasculature, but possibly via its influence on other non-renal splanchnic organs.