Central and peripheral (reflex) mechanisms govern fluid balance. In the central nervous system, noradrenergic pathways have been shown to be involved in fluid balance. The atrial stretch reflex plays an important role in fluid balance. Stimulation of the atrial receptors mediate an increase in heart rate, a reduction in salt and water intake, and an increased natriuresis and diuresis. The first hypothesis is that information about the atrial distension (increased volume) is relayed via to the forebrain (median preoptic nucleus and paraventricular nucleus) via noradrenergic cell bodies in A5 and A6 in the midbrain; the peripheral limb of the reflex is an increased and noradrenergic activity in the heart related to tachcardia, and decreased noradrenergic activity in the kidney related to diuresis and natriuresis. Atrial receptors will be stimulated by inflating a balloon-tipped catheter placed at the veno-atrial junction. Changes in noradrenergic activity in various tissues will be assessed by measuring turnover of norepinephrine. Subsequently, the influence of stimulation of central sites (mentioned above) on the peripheral response (electrophysiological nerve recording-renal) to atrial stretch will elucidate their specific role in the atrial stretch reflex. We have demonstrated that in Dahl salt-sensitive (S) rats, known to have an impaired cardiopulmonary reflex, noradrenergic activity is increased in the kidney and in the preoptic and supraoptic nuclei, regions involved in fluid balance. An impaired atrial reflex permitting inappropriately high renal nerve activity resulting in retention of salt and water, represents a possible mechanism for increased arterial pressure. However, it is not known if the atrial stretch reflex is impaired in the Dahl model of hypertension. The second hypothesis is that Dahl S rats have an impaired atrial stretch reflex and that it may be related to abnormal noradrenergic activity in specific forebrain sites. The experiments proposed will allow determination of central and peripheral noradrenergic components of the atrial stretch reflex. An enhanced knowledge of these mechanisms will greatly contribute to our understanding of the physiology and pathophysiology of cardiovascular control and may have important implications for pathological conditions such as hypertension.
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