Role of corticotrophin-releasing factor in effects of leptin on sympathetic nerve activity and arterial pressure

Leptin and corticotrophin-releasing factor increase sympathetic nervous act ivity to interscapular brown adipose tissue, kidneys, and adrenal glands. L eptin is known to increase hypothalamic corticotrophin-releasing factor. In this study, we tested the hypothesis that leptin-dependent increases in sy mpathetic nervous activity are mediated through increases in central nervou s system corticotrophin-releasing factor activity. We examined the effects of intracerebroventricular administration of corticotrophin-releasing facto r and intravenous leptin on sympathetic nervous activity to interscapular b rown adipose tissue through multifiber neurography in anesthetized Sprague- Dawley rats pretreated with intracerebroventricular alpha-helical corticotr ophin-releasing factor(9-41) (corticotrophin-releasing factor receptor anta gonist) or vehicle. Centrally administered corticotrophin-releasing factor substantially increased interscapular brown adipose tissue sympathetic nerv ous activity. The responses to corticotrophin-releasing factor were substan tially attenuated in animals pretreated with alpha-helical corticotrophin-r eleasing factor(9-41). Leptin-dependent increases in interscapular brown ad ipose tissue sympathetic nervous activity were significantly inhibited by p retreatment with alpha-helical corticotrophin-releasing factor(9-41). Inter estingly, leptin also significantly increased arterial pressure over 6 hour s, but this pressor action was not attenuated by the corticotrophin-releasi ng factor receptor antagonist. These results suggest that corticotrophin-re leasing factor may mediate the sympathoexcitatory effect of leptin on therm ogenic tissue without altering its cardiovascular actions.