The paraventricular-brainstem axis acts as an integrator of autonomic and endocrine function. We hypothesize that oxytocin, a peptidergic transmitter in this pathway, modulates cardiovascular responses and that this is accentuated by sodium. Further we suggest that central oxytocin may be an important an unappreciated neuroendocrine modulator of cardiovascular and hydromineral balance. A key finding in the initial grant period was that interruption of this PVN-brainstem circuit via baroreceptor denervation produces chronic changes in the hypothalamic neurosecretory cells, making them hypersensitive to the effects of sodium. The increased response of the oxytocin system in terms of mRNA expression and peptide secretion is especially intriguing in view of the postulated role of oxytocin as a link between cardiovascular control and salt balance. A research program is proposed to study the peptidergic interactions between PVN and brainstem, the influence of brainstem oxytocin on cardiovascular and sympathetic nervous function, the influence of baroreceptor input and central stimulation on oxytocin mRNA expression and the role of oxytocin in baroreceptor-induced changes in salt intake. The proposal will employ techniques which will allow for the evaluation of central neuronal function, peptide mRNA expression, peptide secretion and physiological responses. Microdialysis will be used for measuring central and systemic oxytocin release, microinjection for the study of cardiovascular and sympathetic responses and in situ hybridization methods for the evaluating of the changes in cellular mRNA levels.
The specific aims of the proposal are: 1) to study PVN-brainstem interactions by examining the effect of PVN stimulation on brainstem oxytocin release and cardiovascular parameters 2) to examine the role of oxytocinergic brainstem pathways to the dorsal vagal complex of the medulla in the regulation of autonomic outflow and cardiovascular function 3) to evaluate the peptide mRNA responses to baroreceptor denervation (time course), hypertonic saline and angiotensin and 4)To determine the role of central oxytocin in baroreceptor-mediated changes in salt intake.
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