The working hypothesis is that NE and 5-HT are neurotransmitters in brain pathways regulating cardiovascular function. The objective is to understand how monoamine systems interact at different levels of the neuroaxis to control sympathetic outflow to vasculature and heart. Our prior work shows: (1) that intracerebroventricular injection of NE antagonists and 5-HT precursor, 5-HTP, depress blood pressure, heart rate and the increase in pressure and sympathetic discharge in response to decreased baroreceptor afferent input by acting in the caudal brainstem; and (2) that these drug effects depend on intact neural connections with higher brain centers. In the proposed experiments, we plan to: (1) localize pathways in which the drugs act by making discrete electrolytic lesions which prevent drug actions; (2) further confirm monoaminergic nature of pathway by seeing in NE antagonist and 5-HTP action are prevented by microinjection of chemicals which destroy NE and 5HT neurons into the localized pathway and by testing effect of inhibiting NE biosynthesis on changes in BCO pressor and sympathetic response induced by electrically stimulating within pathway; (3) use intracerebroventricular NE antagonists, 5-HTP electrolytic and chemical lesions to analyze pathway for depression of BP and sympathetic discharge in response to increased baroreceptor activity; (4) determine if NE and 5-HT pathways modulating baroreceptor responses correspond to pathways mediating "defense response".
NIH ExPorter
NIH ExPorter