Neural regulation of blood pressure by leptin and the related peptides.
Recent biological advances make it possible to discover new peptides associated with obesity. Leptin, neuropeptide Y, corticotrophin-releasing factor (CRF), alpha-melanocyte stimulating hormone (alpha-MSH), and cocaine- and amphetamine-regulated transcript (CART) peptides are known to participate in appetite and feeding behavior. Various lines of evidence suggest that these peptides participate not only in feeding behavior but also in cardiovascular and sympathetic regulations. Both leptin and ghrelin are secreted from the peripheral tissue; then they reach the brain to modulate sympathetic activity. These two peptides seem to play important roles to transmit peripheral metabolic information to the brain, and to convert it to cardiovascular and sympathetic information. Leptin activates neurons containing alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript peptides, resulting in increases in sympathetic activity and blood pressure. Cardiovascular action of alpha-melanocyte stimulating hormone is mediated through melanocortin-4 receptor, and agouti-related protein (AGRP) plays a role as an endogenous melanocortin-4 receptor antagonist. In contrast, ghrelin and neuropeptide Y in the brain suppress sympathetic activity and decrease blood pressure. Depressor and sympathoinhibitory effects of central neuropeptide Y are inhibited by leptin. Furthermore, central ghrelin modulates baroreflex control of renal sympathetic nerve activity and heart rate. Thus, leptin and the related peptides, which participate in appetite and feeding behavior, seem to function together to regulate cardiovascular system and sympathetic nerve activity, and may play a key role in the association between obesity and hypertension.
Matsumura
Kiyoshi
K
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. matsumk@intmed2.med.kyushu-u.ac.jp
Tsuchihashi
Takuya
T
Fujii
Koji
K
Iida
Mitsuo
M
D054369:Agouti-Related Protein; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D054439:Ghrelin; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009478:Neuropeptide Y / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D000068797:Orexins; D036361:Peptide Hormones / Q000502:physiology; D011506:Proteins / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D000521:alpha-MSH / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
C515198:AGRP protein, human; D054369:Agouti-Related Protein; D002352:Carrier Proteins; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D036361:Peptide Hormones; D011506:Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000521:alpha-MSH; D003346:Corticotropin-Releasing Hormone