CONTROL OF NORADRENERGIC MECHANISMS IN ATRIAL REFLEX

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.