Project Details


Acute blood loss produces a constellation of physiological responses that
aid in the restoration of cardiovascular homeostasis. These compensatory
responses include increased constriction of blood vessel and cardiac output
brought about, in part, by a stimulation of the sympathetic nervous.
However, beyond a critical level of blood loss a seemingly paradoxical
reversal of the automatic compensations occurs, leading to a dramatic
decrease in arterial pressure. This decompensatory phase of the hemorrhage
response is associated with an inhibition of some sympathetic nerves and
a decrease in peripheral vascular resistance. Hemorrhage-induced
sympathoinhibition is triggered by the activation of cardiac vagal
afferents that project to the nucleus tractus solitarius (NTS), but the
central mechanism underlying this response remains unknown. Hemorrhage-
induced sympahtoinhibition may be produced by a inhibition of neurons in
the rostral ventrolateral medulla (RVLM) that provide the major source of
tonic excitatory drive to sympathetic vasoconstrictor nerves. Several
reflexes that are also triggered by afferents to NTS inhibit sympathetic
vasomotor tone (e.g. baroreceptor reflex and Bexold-Jarish reflex)by
inhibiting RVLM presympathetic neurons via the excitation of a GABAerigic
projection from the caudal ventrolateral medulla (CVLM). However, in
contrast to these other reflexes, centrally-acting opiates appears to be
crucial for hemorrage-induced sympathoinhibition.. Opiate receptor blockade
centrally but not peripherally can reverse hemorrhage-induced
sympathoinhibition, but the central mechanism underlying the opiate
contribution to this response is not known. Because opiates can inhibit
RVLM presympathetic neurons directly, hemorrhage-induced sympathoinhibition
may occur by a release of opiates into RVLM that is independent of an
inhibilitory projection from V|CVLM. This application has two goals: 1)
to reveal the central circuitry for hemorrhage-induced symphathoinhibition,
and 2) to determine the role of opiate peptides in this process.
Effective start/end date1/01/9731/12/98


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