Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.
OBJECTIVE
Melanocyte stimulating hormones (MSHs, melanocortins) have important roles in feeding and energy metabolism and in inflammation. Recent observations have uncovered major functions for these peptides, particularly gamma-MSH, in cardiovascular regulation and sodium metabolism.


RESULTS
Both alpha- and gamma-MSH acutely elevate blood pressure and heart rate through central stimulation of sympathetic nervous outflow. This action of alpha-MSH is mediated by the melanocortin 4 receptor (MC4R), whereas sympathetic nervous stimulation by gamma-MSH does not involve its receptor MC3R but rather is likely due to activation of a sodium channel in the central nervous system. In contrast, gamma-MSH deficiency in rodents, or disruption of MC3R, leads to marked salt-sensitive hypertension, again through a central mechanism: a small dose of exogenous peptide delivered into the cerebroventricular system of mice with gamma-MSH deficiency restores blood pressure to normal. This salt-sensitive hypertension is accompanied by the development of insulin resistance; the mechanism linking these two consequences of a high-salt diet is not yet known but may involve activation of the sympathetic nervous system.


CONCLUSIONS
The study of MSH peptides in blood pressure regulation offers a new opportunity to gain insight into the mechanisms underlying salt sensitivity and its link to insulin resistance, and to new therapies.
Humphreys
Michael H
MH
Division of Nephrology, San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94143, USA. mhumphreys@medsfgh.ucsf.edu
D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism*; D009074:Melanocyte-Stimulating Hormones / Q000502:physiology*; D044101:Receptors, Melanocortin / Q000502:physiology; D012377:Rodentia / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D044101:Receptors, Melanocortin; D009074:Melanocyte-Stimulating Hormones; D012964:Sodium