Modulation of blood pressure by central melanocortinergic pathways

New England Journal of Medicine

Volumn 360, Issue 1, 2009, Pages 44-52

  Greenfield, Jerry R ^a   Miller, Jeffrey W ^d   Keogh, Julia M ^a   Henning, Elana ^a   Satterwhite, Julie H ^d   Cameron, Gregory S ^d   Astruc, Beatrice ^e   Mayer, John P ^d   Brage, Soren ^b   See, Teik Choon ^c   Lomas, David J ^c   O'Rahilly, Stephen ^a   Farooqi, I Sadaf ^a,d  

^a University of Cambridge Metabolic Research Laboratories   (France)

^b Medical Research Council Epidemiology Unit   (France)

^c INSTITUTE OF METABOLIC SCIENCE   (United Kingdom)

^d ADDENBROOKE S HOSPITAL   (United Kingdom)

^e Biotrial   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIHYPERTENSIVE AGENT; INSULIN; LY 2112688; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN RECEPTOR AGONIST; NORADRENALIN; PLACEBO; UNCLASSIFIED DRUG; CATECHOLAMINE;

ADULT; ADVERSE OUTCOME; ARTICLE; ASTHENIA; AUTONOMIC NERVOUS SYSTEM FUNCTION; CATECHOLAMINE URINE LEVEL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIASTOLIC BLOOD PRESSURE; DOUBLE BLIND PROCEDURE; FEMALE; HEADACHE; HEART RATE; HETEROZYGOSITY; HUMAN; HYPERINSULINEMIA; HYPERTENSION; INSULIN BLOOD LEVEL; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; NAUSEA AND VOMITING; OBESITY; PHENOTYPE; PREVALENCE; PRIORITY JOURNAL; SYSTOLIC BLOOD PRESSURE; WAKEFULNESS; AUTONOMIC NERVOUS SYSTEM; BLOOD PRESSURE; DOSE RESPONSE; DRUG EFFECT; DRUG POTENTIATION; GENETICS; GENOTYPE; HETEROZYGOTE; METABOLISM; MUTATION; PHYSIOLOGY; SIGNAL TRANSDUCTION; SLEEP; URINE;

ADULT; AUTONOMIC NERVOUS SYSTEM; BLOOD PRESSURE; CATECHOLAMINES; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; GENOTYPE; HEART RATE; HETEROZYGOTE; HUMANS; HYPERTENSION; MALE; MUTATION; OBESITY; OVERWEIGHT; PREVALENCE; RECEPTOR, MELANOCORTIN, TYPE 4; SIGNAL TRANSDUCTION; SLEEP;

EID: 58249087146     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa0803085     Document Type: Article

References (28)

1. Dustan HP. Research contributions toward prevention of cardiovascular disease: research related to the underlying mechanisms in hypertension. Circulation 1979;60: 1566-8.
2. Garrison RJ Kannel WB, Stokes J III, Castelli WP. Incidence and precursors of hypertension in young adults: the Framing-ham Offspring Study. Prev Med 1987;16: 235-51.
3. Hall JE. Mechanisms of abnormal renal sodium handling in obesity hypertension. Am J Hypertens 1997;10:49S-55S.
4. Kassab S, Kato T, Wilkins FC, Chen R, Hall JE, Granger JP. Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 1995;25:893-7.
5. Hall JE, Brands MW, Hildebrandt DA, Kuo J, Fitzgerald S. Role of sympathetic nervous system and neuropeptides in obesity hypertension. Braz J Med Biol Res 2000;33:605-18.
6. Farooqi IS, O'Rahilly S. Monogenic obesity in humans. Annu Rev Med 2005;56:443-58.
7. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000;404:661-71.
8. Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neu-rosci 2005;8:571-8.
9. Tallam LS, Stec DE, Willis MA, da Silva AA, Hall JE. Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsu-linemia, and hyperleptinemia. Hypertension 2005;46:326-32.
10. Ni XP, Butler AA, Cone RD, Humphreys MH. Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones. J Hypertens 2006;24:2239-46.
11. Kuo JJ, da Silva AA, Tallam LS, Hall JE. Role of adrenergic activity in pressor responses to chronic melanocortin receptor activation. Hypertension 2004;43:370-5.
12. Kuo JJ, Silva AA, Hall JE. Hypothalamic melanocortin receptors and chronic regulation of arterial pressure and renal function. Hypertension 2003;41:768-74.
13. Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the mel-anocortin 4 receptor gene. N Engl J Med 2003;348:1085-95.
14. Larsen LH, Echwald SM, Sørensen TI, Andersen T, Wulff BS, Pedersen O. Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. J Clin Endocrinol Metab 2005;90:219-24.
15. Stutzmann F, Tan K, Vatin V, et al. Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependant penetrance in multigenerational pedigrees. Diabetes 2008;57:2511-8.
16. Alharbi KK, Spanakis E, Tan K, et al. Prevalence and functionality of paucimor-phic and private MC4R mutations in a large, unselected European British population, scanned by meltMADGE. Hum Mutat 2007;28:294-302.
17. Huszar D, Lynch CA, Fairchild-Hunt-ress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997;88:131-41.
18. Mertens IL, Van Gaal LF. Overweight, obesity, and blood pressure: the effects of modest weight reduction. Obes Res 2000;8:270-8.
19. Rocchini AP, Moorehead CP, DeRemer S, Bondie D. Pathogenesis of weight-related changes in blood pressure in dogs. Hypertension 1989;13:922-8.
20. Hall JE. Pathophysiology of obesity hypertension. Curr Hypertens Rep 2000;2:139-47.
21. Hall JE, Summers RL, Brands MW, Keen H, Alonso-Galicia M. Resistance to metabolic actions of insulin and its role in hypertension. Am J Hypertens 1994;7:772-88.
22. Fan W, Dinulescu DM, Butler AA, Zhou J, Marks DL, Cone RD. The central melanocortin system can directly regulate serum insulin levels. Endocrinology 2000;141:3072-9.
23. Vaz M, Jennings G, Turner A, Cox H, Lambert G, Esler M. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation 1997;96:3423-9.
24. Brito MN, Brito NA, Baro DJ, Song CK, Bartness TJ. Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation. Endocrinology 2007;148:5339-47.
25. Song CK, Jackson RM, Harris RB, Richard D, Bartness TJ. Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue. Am J Physiol Regul Integr Comp Physiol 2005;289: R1467-R1476.
26. Rosenbaum M, Goldsmith R, Bloom-field D, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005;115:3579-86.
27. Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL. Sympathetic and car-diorenal actions of leptin. Hypertension 1997;30:619-23.
28. Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI. Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest 1997;100:270-8.