The general objective of the proposed research is to examine the roles of two neuropeptides, corticotropin-releasing factor (CRF) and bombesin, in the central nervous system (CNS) regulation of the baroreceptor reflex. Baroreflex control of blood pressure is effected primarily through adjustments of sympathetic (SNS) and parasympathetic (PNS) outflow to the heart and vasculature. Since CRF and bombesin have profound CNS actions to influences SNA and PNS activity, blood pressure and heart rate, these peptides may be potential transmitters utilized in CNS baroreflex pathways. Moreover, alterations in CRF or bombesin transmission may underlie CNS-mediated abnormalities of baroreflex function observed in hypertension. Baroreflex function in conscious, freely-moving rats will be assessed by deriving stimulus-response curves relating changes in pulse inteval (PI) to changes of mean arterial pressure (MAP) in rats receiving CNS injections of CRF, bombesin and control solutions. This will be repeated in rats subjected to selective or combined blockade of peripheral SNS and PNS transmission. These studies will determine whether CFR and bombesin modulate baroreflex function via baroreceptor-dependent of -independent CNS pathways and whether these effects are mediated by changes in SNS or PNS outflow. To determine whether endogenous CRF and bombesin participate in the tonic regulation of baroreflex function, these studies will be repeated in rats passively immunized against these peptides and CRF and bombesin will be measured in discrete brain regions following sinoaortic denervation. The studies outlined above will be repeated in spontaneously hypertensive rats (SHR) to determine whether CRF and bombesin participate in the development of abnormal baroreflex function observed in these rats. The SHR exhibits exaggerated SNS and hormonal responses to stress and impaired baroreflex control of heart rate. CRF acts in the CNS to increase SNS outflow, stimulate release of stress hormones, and elevate MAP and heart rate, and thus may contribute to the hypertension and pronounced stress responses that characterize the SHR. The health relevancy of these studies is overt in that baroreflex function is modified by stressful stimuli and hypertension. Basic knowledge regarding the CNS transmitters involved in the regulation of baroreflex function is prerequisite to understanding possible abnormalities that underlie cardiovascular disease.
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