CENTRAL CARDIOVASCULAR CONTROL: NORMAL AND HYPERTENSIVE

Recent research on central cardiovascular control indicates the existence
of a population of neurons in the lateral medullary reticular formation
that provides a final common pathway conveying the excitatory drive to the
spinal sympathetic nucleus that is critical for the maintenance of basal
sympathetic tone. As described in the proposal, the characterization of
these neurons will provide new information on the central neural mechanisms
underlying the sympathetic control of blood pressure. The proposed studies
will focus on the hypothesis that neurons in the rostral ventrolateral
medulla (RVL) that contain the adrenaline-synthesizing enzyme,
phenylethanolamine N-methyltransferase (PNMT) mediate the tonic bulbospinal
excitation of sympathetic preganglionic neurons (SPN) necessary for the
support of resting blood pressure. Extracellular recording and antidromic
activation techniques are combined with baroreceptor reflex activation and
computer-aided analysis to identify sympathoexcitatory neurons in RVL that
project to the sympathetic intermediolateral nucleus. Immunocytochemical
staining is used to determine the proximity of the recording sites of these
neurons to the locations of neurons containing PNMT (C1 cell group).
Additional experiments are designed to examine (1) the baroreceptor reflex
pathway providing an inhibitory control of the activity of these cells and
(2) the activation of RVL sympathetic neurons from hypothalamic pressor
sites. Microiontophoretic application of antagonist drugs will be used to
classify the transmitter system(s) mediating the effects of RVL activation
on the activity of SPNs. Together these data would not only increase our
knowledge of the basic neural mechanisms involved in central blood pressure
regulation, they might also provide a basis for (1) the evaluation of the
role of altered neural function in hypertensive disease and (2) the design
of pharmacologic approaches to antihypertensive therapy. The former
possibility is tested in a final series of experiments to determine if the
sympathetic hyperactivity of the spontaneously hypertensive rat is
associated with increased activity of the sympathoexcitatory neurons in the
C1 region of the RVL.