The experiments of this proposal are designed to elucidate the mechanism(s) through which dietary sodium intake affects sympathetic nervous system control of the heart and vasculature. The overall objective of the proposal is to test the hypothesis that the renin angiotensin system (RAS), through its responsiveness to sodium intake, modulates peripheral sympathetic nervous system function so that the effects of the sympathetic neurons on the cardiovascular system are appropriate to the level of sodium intake. Information to be provided by these experiments has important implications regarding the role of dietary sodium intake patterns in the development of hypertensive disease. In addition, a better understanding will be gained of the adaptations of the sympathetic nervous system to the therapeutic modality of reducing sodium intake.
The specific aims of these experiments are to determine the effects of a range of dietary sodium intakes on: 1) hemodynamic responses to peripheral sympathetic neural stimulation, 2) sympathetic neuronal and adrenal medullary catecholamine disposition, to include measurement of tissue content, synthesis, release and uptake, 3) heart and vascular smooth muscle responsiveness to neurotransmitter (and appropriate alpha- and beta-receptor agonists) and 4) modulation of sympathetic function by the RAS and 5) to relate the influences of dietary sodium intake tothe conscious animal. To accomplish these aims, three experimental systems will be used, each varying in level of complexity, and each suited to provide unique information. The pithed rat preparation will be used to test peripheral sympathetic neuronal function in the absence of tonic neural ouflow and operative reflexes. An in vitro system, the isolated perfused mesentery, will be used to study postganglionic neuronal function and effector organ responsiveness in the absence of the hormonal and hemodynamic variables existing in the intact animal. The third model, the conscious rat will be used to test the operation of the sympathetic nervous system in its most complete form. Two of the models, the conscious rat and pithed rat were selected because the state of activation of the RAS is related to the dietary sodium intake. Thus sympathetic function may be assessed first in the presence and then following blockade of RAS influences. The in vitro system provides an opportunity to study vascular function first in the absence of a functional RAS and then in a controlled fashion by administration of angiotensin II.
