Role of corticotrophin-releasing factor in effects of leptin on sympathetic nerve activity and arterial pressure.
Leptin and corticotrophin-releasing factor increase sympathetic nervous activity to interscapular brown adipose tissue, kidneys, and adrenal glands. Leptin is known to increase hypothalamic corticotrophin-releasing factor. In this study, we tested the hypothesis that leptin-dependent increases in sympathetic nervous activity are mediated through increases in central nervous system corticotrophin-releasing factor activity. We examined the effects of intracerebroventricular administration of corticotrophin-releasing factor and intravenous leptin on sympathetic nervous activity to interscapular brown adipose tissue through multifiber neurography in anesthetized Sprague-Dawley rats pretreated with intracerebroventricular alpha-helical corticotrophin-releasing factor(9-41) (corticotrophin-releasing factor receptor antagonist) or vehicle. Centrally administered corticotrophin-releasing factor substantially increased interscapular brown adipose tissue sympathetic nervous activity. The responses to corticotrophin-releasing factor were substantially attenuated in animals pretreated with alpha-helical corticotrophin-releasing factor(9-41). Leptin-dependent increases in interscapular brown adipose tissue sympathetic nervous activity were significantly inhibited by pretreatment with alpha-helical corticotrophin-releasing factor(9-41). Interestingly, leptin also significantly increased arterial pressure over 6 hours, but this pressor action was not attenuated by the corticotrophin-releasing factor receptor antagonist. These results suggest that corticotrophin-releasing factor may mediate the sympathoexcitatory effect of leptin on thermogenic tissue without altering its cardiovascular actions.
Correia
M L
ML
Specialized Center of Research in Hypertension Genetics, Department of Internal Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
Morgan
D A
DA
Mitchell
J L
JL
Sivitz
W I
WI
Mark
A L
AL
Haynes
W G
WG
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology* / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D006727:Hormone Antagonists; D020738:Leptin; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)