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 date||1/01/97 → 31/12/98|
- National Heart, Lung, and Blood Institute
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