Modulation of blood pressure by central melanocortinergic pathways.

Weight gain and weight loss are associated with changes in blood pressure through unknown mechanisms. Central melanocortinergic signaling is implicated in the control of energy balance and blood pressure in rodents, but there is no information regarding such an association with blood pressure in humans. The authors assessed blood pressure, heart rate, and urinary catecholamines in overweight or obese subjects with a loss-of-function mutation in MC4R, the gene encoding the melanocortin 4 receptor, and in equally overweight control subjects. They also examined the effects of an MC4R agonist administered for 7 days in 28 overweight or obese volunteers.

[1]  J. Kuo,et al.  Role of Adrenergic Activity in Pressor Responses to Chronic Melanocortin Receptor Activation , 2004, Hypertension.

[2]  R. Cone,et al.  The central melanocortin system can directly regulate serum insulin levels. , 2000, Endocrinology.

[3]  W. Kannel,et al.  Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. , 1987, Preventive medicine.

[4]  A. Rocchini,et al.  Pathogenesis of Weight‐Related Changes in Blood Pressure in Dogs , 1989, Hypertension.

[5]  S. Heymsfield,et al.  Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. , 2005, The Journal of clinical investigation.

[6]  S. Fitzgerald,et al.  Role of sympathetic nervous system and neuropeptides in obesity hypertension. , 2000, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[7]  S. O’Rahilly,et al.  Monogenic obesity in humans. , 2005, Annual review of medicine.

[8]  G. Bray,et al.  Pathophysiology of obesity. , 1992, The American journal of clinical nutrition.

[9]  D. Stec,et al.  Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia , 2005, Hypertension.

[10]  C. K. Song,et al.  Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation. , 2007, Endocrinology.

[11]  R. Cone,et al.  Targeted Disruption of the Melanocortin-4 Receptor Results in Obesity in Mice , 1997, Cell.

[12]  A. Lerner,et al.  Effect of Alpha- and Beta-Melanocyte Stimulating Hormones on the Skin Colour of Man , 1961, Nature.

[13]  R. Cone,et al.  Differential effects of melanocortin peptides on neural melanocortin receptors. , 1994, Molecular pharmacology.

[14]  V. Crowley.  Overview of human obesity and central mechanisms regulating energy homeostasis , 2008, Annals of clinical biochemistry.

[15]  G. Jennings,et al.  Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. , 1997, Circulation.

[16]  A. Mark,et al.  Receptor-mediated regional sympathetic nerve activation by leptin. , 1997, The Journal of clinical investigation.

[17]  S. O’Rahilly,et al.  Prevalence of Melanocortin-4 Receptor Deficiency in Europeans and Their Age-Dependent Penetrance in Multigenerational Pedigrees , 2008, Diabetes.

[18]  A. Mark,et al.  Sympathetic and cardiorenal actions of leptin. , 1997, Hypertension.

[19]  Alfio Bertolini,et al.  Brain effects of melanocortins. , 2009, Pharmacological research.

[20]  J. Granger,et al.  Renal denervation attenuates the sodium retention and hypertension associated with obesity. , 1995, Hypertension.

[21]  R. Cone,et al.  The Central Melanocortin System and Energy Homeostasis , 1999, Trends in Endocrinology & Metabolism.

[22]  J. Shutter,et al.  Overexpression of Agrt leads to obesity in transgenic mice , 1997, Nature Genetics.

[23]  S. Woods,et al.  Central nervous system control of food intake , 2000, Nature.

[24]  R. Adan,et al.  Melanocortins and cardiovascular regulation. , 1998, European journal of pharmacology.

[25]  R. Cone,et al.  Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones , 2006, Journal of hypertension.

[26]  M. Mortrud,et al.  The cloning of a family of genes that encode the melanocortin receptors. , 1992, Science.

[27]  R. Summers,et al.  Resistance to metabolic actions of insulin and its role in hypertension. , 1994, American journal of hypertension.

[28]  Tim Cheetham,et al.  Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. , 2003, The New England journal of medicine.

[29]  C. K. Song,et al.  Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[30]  J. Kuo,et al.  Hypothalamic Melanocortin Receptors and Chronic Regulation of Arterial Pressure and Renal Function , 2003, Hypertension.

[31]  H. Dustan.  Research contributions toward prevention of cardiovascular disease. Research related to the underlying mechanisms in hypertension. , 1979, Circulation.

[32]  S. Watson,et al.  Molecular cloning of a novel melanocortin receptor. , 1993, The Journal of biological chemistry.

[33]  M. Mortrud,et al.  Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. , 1994, Molecular endocrinology.

[34]  A V Vergoni,et al.  Role of melanocortins in the central control of feeding. , 2000, European journal of pharmacology.

[35]  A. Oswal,et al.  The leptin melanocortin pathway and the control of body weight: lessons from human and murine genetics , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[36]  G. Barsh,et al.  Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. , 1997, Science.

[37]  R. Cone.  Anatomy and regulation of the central melanocortin system , 2005, Nature Neuroscience.

[38]  L. V. Van Gaal,et al.  Overweight, obesity, and blood pressure: the effects of modest weight reduction. , 2000, Obesity research.

[39]  P. Boutin,et al.  Genetics of human obesity. , 2001, Best practice & research. Clinical endocrinology & metabolism.

[40]  W. Elliott.  Modulation of Blood Pressure by Central Melanocortinergic Pathways , 2010 .

[41]  J. Wikberg,et al.  Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA , 1992, FEBS letters.

[42]  O. Pedersen,et al.  Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. , 2005, The Journal of clinical endocrinology and metabolism.

[43]  D. Lawlor,et al.  Prevalence and functionality of paucimorphic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE , 2007, Human mutation.

[44]  J. Hall.  Pathophysiology of obesity hypertension , 2000, Current hypertension reports.

[45]  Victor J. Hruby,et al.  Role of melanocortinergic neurons in feeding and the agouti obesity syndrome , 1997, Nature.

[46]  J. Hall,et al.  Mechanisms of abnormal renal sodium handling in obesity hypertension. , 1997, American journal of hypertension.

[47]  J. Harrold,et al.  Melanocortin-4 receptors, β-MSH and leptin: Key elements in the satiety pathway , 2006, Peptides.

[48]  J. B. Tatro.  Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides. , 1996, Neuroimmunomodulation.