Genetic disruption of γ-melanocyte–stimulating hormone signaling leads to salt-sensitive hypertension in the mouse
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The γ-melanocyte-stimulating hormone (γ-MSH) is a natriuretic peptide derived from the N-terminal region of proopiomelanocortin (POMC). Evidence suggests that it may be part of the coordinated response to a low-sodium diet (LSD). We tested the effect of the HSD (8% NaCl) compared with LSD (0.07%) on mean arterial pressure (MAP) in mice with targeted disruption of the PC2 gene (PC2(–/–)), necessary for processing of POMC into γ-MSH, or the melanocortin receptor 3 gene (Mc3r(–/–); the receptor for MSH). In wild-type mice, HSD for 1 week did not alter MAP versus LSD mice, but plasma γ-MSH immunoreactivity was more than double the LSD value. In contrast, in PC2(–/–) mice, MAP on the LSD was not greater than in wild-type mice, but plasma γ-MSH was reduced to one-seventh the wild-type value. On the HSD, MAP rose to a markedly hypertensive level while plasma γ-MSH concentration remained severely depressed. Intravenous infusion of γ-MSH (0.2 pmol/min) for 30 min to PC2(–/–) mice after 1 week of HSD lowered MAP from hypertensive levels to normal; infusion of α-MSH at the same rate had no effect. Injection of 60 fmol of γ-MSH into the lateral cerebral ventricle of hypertensive mice also lowered MAP to normal. Administration of a stable analogue of γ-MSH intra-abdominally by microosmotic pump to PC2(–/–) mice prevented the development of hypertension when ingesting the HSD. In mice with targeted disruption of the Mc3r gene, the HSD also led to marked hypertension accompanied by elevated plasma levels of γ-MSH; infusion of exogenous γ-MSH to these mice had no effect on MAP. These results strongly suggest that PC2-dependent processing of POMC into γ-MSH is necessary for the normal response to the HSD. γ-MSH deficiency results in marked salt-sensitive hypertension that is rapidly improved with exogenous γ-MSH through a central site of action. α-MSH infused at the same rate had no effect on MAP, indicating that the hypertension is a specific consequence of impaired POMC processing into γ-MSH. Absence of Mc3r produces γ-MSH resistance and hypertension on the HSD. These findings demonstrate a novel pathway mediating salt-sensitivity of blood pressure.
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Mice with genetic deficiency of MC3R or PC2 increase salt sensitivity of blood pressure.
“Support for this hypothesis comes from studies showing that mice with genetic deficiency of MC3R or PC2, which reduces formation of γ-MSH, increase salt sensitivity of BP in mice [22].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [22]
Cites
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030 · see citing works
Molecular Mechanisms of Human Hypertension
Lifton, R. P., Gharavi, A. G., & Geller, D. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00241-0 · Cited by 1,686 · see citing works
The Kidney: Physiology and Pathophysiology
(1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-6-544_3 · Cited by 1,681 · see citing works
Salt Sensitivity of Blood Pressure in Humans
Weinberger, M. H. (1996) · Hypertension · doi:10.1161/01.hyp.27.3.481 · Cited by 857 · see citing works
Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., Entwistle, M. L., Simerly, R. B., & Cone, R. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.8856 · Cited by 722 · see citing works
A Unique Metalolic Sysdrone Causes Obesity in the Melanocortin-3 Receptor-Deficient Mouse
Butler, A. A., Kesteson, R. A., Khong, K., Cullen, M. J., Pelleymounter, M. A., DeKoning, J., Baetscher, M., & Cone, R. D. (2000) · Endocrinology · doi:10.1210/endo.141.9.7791 · Cited by 703 · see citing works
Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension
John, S. W. M., Krege, J. H., Oliver, P. M., Hagaman, J. R., Hodgin, J. B., Pang, S. C.-N., Flynn, T. G., & Smithies, O. (1995) · Science · doi:10.1126/science.7839143 · Cited by 637 · see citing works
Benjannet, S., Rondeau, N., Day, R. W., Chrétien, M., & Seidah, N. G. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.9.3564 · Cited by 588 · see citing works
Sawyer, T. K., Sanfilippo, P. J., Hruby, V. J., Engel, M. H., Heward, C. B., Burnett, J. B., & Hadley, M. E. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.10.5754 · Cited by 579 · see citing works
Yan, W., Wu, F., Morser, J., & Wu, Q. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.150149097 · Cited by 490 · see citing works
Proteolytic Processing in the Secretory Pathway
Zhou, A., Webb, G. C., Zhu, X., & Steiner, D. F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20745 · Cited by 457 · see citing works
Subtle Acquired Renal Injury as a Mechanism of Salt-Sensitive Hypertension
Johnson, R. J., Herrera-Acosta, J., Schreiner, G. F., & Rodríguez‐Iturbe, B. (2002) · New England Journal of Medicine · doi:10.1056/nejmra011078 · Cited by 443 · see citing works
Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2
Furuta, M., Yano, H., Zhou, A., Rouillé, Y., Holst, J. J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H., & Steiner, D. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6646 · Cited by 430 · see citing works
Salt sensitivity in hypertension. Renal and cardiovascular implications.
Campese, V. M. (1994) · Hypertension · doi:10.1161/01.hyp.23.4.531 · Cited by 344 · see citing works
New aspects on the melanocortins and their receptors
Wikberg, J. E. S., Muceniece, R., Mandrika, I., Prūsis, P., Lindblom, J., Post, C., & Skottner, A. (2000) · Pharmacological Research · doi:10.1006/phrs.2000.0725 · Cited by 318 · see citing works
Salt-sensitive hypertension in endothelin-B receptor–deficient rats
Gariepy, C. E., Ohuchi, T., Williams, S. C., Richardson, J. A., & Yanagisawa, M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8609 · Cited by 291 · see citing works
Zhou, A., Bloomquist, B. T., & Mains, R. E. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53918-1 · Cited by 262 · see citing works
Distribution of cDNA for melanocortin receptor subtypes in human tissues.
Chhajlani, V. (1996) · PubMed · Cited by 213 · see citing works
A Comprehensive Review of the Salt and Blood Pressure Relationship
Muntzel, M. S., & Drüeke, T. B. (1992) · American Journal of Hypertension · doi:10.1093/ajh/5.4s.1s · Cited by 181 · see citing works
Severe Defect in Proglucagon Processing in Islet A-cells of Prohormone Convertase 2 Null Mice
Furuta, M., Zhou, A., Webb, G. C., Carroll, R., Ravazzola, M., Orci, L., & Steiner, D. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103362200 · Cited by 164 · see citing works
Carey, R. M. (2001) · Hypertension · doi:10.1161/hy0901.096422 · Cited by 160 · see citing works
Li, S.-J., Varga, K., Archer, P., Hruby, V. J., Sharma, S. D., Kesterson, R. A., Cone, R. D., & Kunos, G. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-16-05182.1996 · Cited by 152 · see citing works
Salt-Sensitive Hypertension in Bradykinin B2Receptor Knockout Mice
Alfie, M. E., Yang, X.-P., Hess, F. J., & Carretero, O. A. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1076 · Cited by 119 · see citing works
The physiological role of melanocortin receptors
Schiöth, H. B. (2001) · Vitamins and hormones · doi:10.1016/s0083-6729(01)63007-3 · Cited by 110 · see citing works
Localization and Quantitation of β-Endorphin in Human Brain and Pituitary
Wilkes, M. M., WATKINS, W. B., Stewart, R. D. H., & Yen, S. S. C. (2008) · Neuroendocrinology · doi:10.1159/000122985 · Cited by 92 · see citing works
Loss of cytoskeletal support is not sufficient for anoxic plasma membrane disruption in renal cells
Chen, J., Dai, J., Grant, R. L., Doctor, R. B., Sheetz, M. P., & Mandel, L. J. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.272.4.c1319 · Cited by 92 · see citing works
Defective Prodynorphin Processing in Mice Lacking Prohormone Convertase PC2
Berman, Y. L., Mzhavia, N., Polonskaia, A., Furuta, M., Steiner, D. F., Pintar, J. E., & Devi, L. A. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751763.x · Cited by 87 · see citing works
Gruber, K. A., & Callahan, M. F. (1989) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1989.257.4.r681 · Cited by 70 · see citing works
Allen, R. G., Peng, B. W., Pellegrino, M. J., Miller, E. D., Grandy, D. K., Lundblad, J. R., Washburn, C. L., & Pintar, J. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-16-05864.2001 · Cited by 68 · see citing works
Natriuresis Induced by Alpha and Beta Melanocyte Stimulating Hormone (MSH) in Rats
Orías, R., & McCann, S. M. (1972) · Endocrinology · doi:10.1210/endo-90-3-700 · Cited by 58 · see citing works
Lin, S., Chaves, C., Wiedemann, E., & Humphreys, M. H. (1987) · Hypertension · doi:10.1161/01.hyp.10.6.619 · Cited by 46 · see citing works
Wildt, D. J. D., Krugers, H. J., Kasbergen, C. M., de Lang, H., & Versteeg, D. H. G. (1993) · European Journal of Pharmacology · doi:10.1016/0014-2999(93)90362-l · Cited by 41 · see citing works
GAMMA–2 MSH IS NATRIURETIC IN THE RAT
Lymangrover, J. R., Buckalew, V. M., Harris, J., KLEIN, M. C., & Gruber, K. A. (1985) · Endocrinology · doi:10.1210/endo-116-3-1227 · Cited by 34 · see citing works
Ni, X.-P., Bhargava, A., Pearce, D., & Humphreys, M. H. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00279.2005 · Cited by 34 · see citing works
Wildt, D. J. D., Ven, J. C. V. D., Bergen, P. V., Lang, H. D., & Versteeg, D. H. G. (1994) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00178205 · Cited by 31 · see citing works
Griffing, G. T., Berelowitz, B. A., Hudson, M., Salzman, R. T., Manson, J. E., Aurecchia, S. A., Melby, J. C., Pedersen, R. C., & Brownie, A. C. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111941 · Cited by 31 · see citing works
Good, D. W., & George), (. T. T. A. O. T. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.4.c931 · Cited by 27 · see citing works
Ni, X.-P., Kesterson, R. A., Sharma, S. D., Hruby, V. J., Cone, R. D., Wiedemann, E., & Humphreys, M. H. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.4.r931 · Cited by 27 · see citing works
Dietary Sodium Intake Modulates Pituitary Proopiomelanocortin mRNA Abundance
Mayan, H., Ling, K. T., Lee, E. Y., Wiedemann, E., Kalinyak, J. E., & Humphreys, M. H. (1996) · Hypertension · doi:10.1161/01.hyp.28.2.244 · Cited by 26 · see citing works
Mechanism of the natriuretic action of gamma-melanocyte-stimulating hormone
Chen, X. W., Ying, W., Valentin, J., Ling, K. T., Lin, S., Wiedemann, E., & Humphreys, M. H. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.272.6.r1946 · Cited by 25 · see citing works
Prorenin activation and prohormone convertases in the mouse As4.1 cell line
Laframboise, M., Reudelhuber, T. L., Jutras, I., Brechler, V., Seidah, N. G., Day, R. W., Gross, K. W., & Deschepper, C. F. (1997) · Kidney International · doi:10.1038/ki.1997.13 · Cited by 20 · see citing works
Ali-Rachedi, A., Ferri, G., Varndell, I. M., Noorden, S. V., Schot, L. P. C., LING, N. C., Bloom, S. R., & Polak, J. M. (2008) · Neuroendocrinology · doi:10.1159/000123588 · Cited by 17 · see citing works
γ2-MSH immunoreactivity in the human heart
Ekman, R., Bjartell, A. S., Lisander, B., & Edvinsson, L. I. (1989) · Life Sciences · doi:10.1016/0024-3205(89)90171-9 · Cited by 17 · see citing works
Franco-Saenz, R. (1984) · JAMA · doi:10.1001/jama.1984.03340430053029 · Cited by 17 · see citing works
Chandramohan, G., Ni, X.-P., Kalinyak, J. E., & Humphreys, M. H. (2001) · Pituitary · doi:10.1023/a:1020746414046 · Cited by 13 · see citing works
Natriuretic and kaliuretic effect of melanocyte-stimulating hormones in hamsters.
Hradec, J., & Horký, K. (1979) · PubMed · Cited by 12 · see citing works
de Wardener, H. E. (1987) · Renal Physiology · doi:10.1007/978-1-4614-7545-3_7 · Cited by 10 · see citing works
An AI Approach to Dynamic Visual Field Testing
Cho, K. W., Liu, X., Loizou, G. D., & Wu, J. X. (1998) · Computers and Biomedical Research · doi:10.1006/cbmr.1998.1473 · Cited by 8 · see citing works
Katori, M., Majima, M., & Hayashi, I. (1998) · PubMed · Cited by 8 · see citing works
Ackermann, U., & Azizi, N. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.6.r1441 · Cited by 7 · see citing works
Idiopathic aldosteronism. A possible disease of the intermediate lobe of the pituitary
Franco-Saenz, R. (1984) · JAMA · doi:10.1001/jama.251.19.2555 · Cited by 3 · see citing works
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Cone, R. D. (2005) · Nature Neuroscience · doi:10.1038/nn1455 · Cited by 1,583 · see citing works
Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases
Meneton, P., Jeunemaı̂tre, X., de Wardener, H. E., & MacGregor, G. A. (2005) · Physiological Reviews · doi:10.1152/physrev.00056.2003 · Cited by 703 · see citing works
Studies on the Physiological Functions of the Melanocortin System
Cone, R. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0034 · Cited by 615 · see citing works
POMC: The Physiological Power of Hormone Processing
Harno, E., Ramamoorthy, T. G., Coll, A. P., & White, A. E. (2018) · Physiological Reviews · doi:10.1152/physrev.00024.2017 · Cited by 265 · see citing works
Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity
Tao, Y. (2005) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.04.012 · Cited by 198 · see citing works
The melanocortin system and energy balance
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Tallam, L. S., Stec, D. E., Willis, M. A., da Silva, A. A., & Hall, J. E. (2005) · Hypertension · doi:10.1161/01.hyp.0000175474.99326.bf · Cited by 148 · see citing works
Ellacott, K. L. J., & Cone, R. D. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1861 · Cited by 134 · see citing works
Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction
Wikberg, J. E. S., & Mutulis, F. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2331 · Cited by 133 · see citing works
Neural melanocortin receptors in obesity and related metabolic disorders
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Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones
Ni, X.-P., Butler, A. A., Cone, R. D., & Humphreys, M. H. (2006) · Journal of Hypertension · doi:10.1097/01.hjh.0000249702.49854.fa · Cited by 88 · see citing works
Melanocortin-3 receptor regulates the normal fasting response
Renquist, B. J., Murphy, J. G., Larson, E. A., Olsen, D., Klein, R. F., Ellacott, K. L. J., & Cone, R. D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201994109 · Cited by 87 · see citing works
Tung, Y. C. L., Piper, S. J., Yeung, D., O’Rahilly, S., & Coll, A. P. (2006) · Endocrinology · doi:10.1210/en.2006-0866 · Cited by 86 · see citing works
Pathophysiological Mechanisms of Salt-Dependent Hypertension
Rodríguez‐Iturbe, B., Romero, F., & Johnson, R. J. (2007) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2007.05.025 · Cited by 85 · see citing works
Sodium Intake and Vascular Stiffness in Hypertension
Safar, M. E., Temmar, M., Kakou, A., Lacolley, P. J., & Thornton, S. N. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.129585 · Cited by 83 · see citing works
Salt feedback on the renin-angiotensin-aldosterone system
Schweda, F. (2014) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-014-1668-y · Cited by 72 · see citing works
After all those fat years: renal consequences of obesity
Wolf, G. (2003) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfg427 · Cited by 63 · see citing works
Physiological roles of the melanocortin MC3 receptor
Renquist, B. J., Lippert, R. N., Sebag, J. A., Ellacott, K. L. J., & Cone, R. D. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.12.025 · Cited by 61 · see citing works
Pathophysiology of melanocortin receptors and their accessory proteins
Novoselova, T. V., Chan, L. F., & Clark, A. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.02.002 · Cited by 58 · see citing works
The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases
Cai, M., & Hruby, V. J. (2016) · Current Protein and Peptide Science · doi:10.2174/1389203717666160226145330 · Cited by 56 · see citing works
Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats
You, P., Hu, H., Chen, Y., Zhao, Y., Yang, Y., Wang, T., Xing, R., Shao, Y., Zhang, W., Li, D., et al. (2016) · Scientific Reports · doi:10.1038/srep34938 · Cited by 53 · see citing works
γ-MSH, sodium metabolism, and salt-sensitive hypertension
Humphreys, M. H. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00365.2003 · Cited by 51 · see citing works
McCormick, J. A., Nelson, J. H., Yang, C., Curry, J. N., & Ellison, D. H. (2011) · Hypertension · doi:10.1161/hypertensionaha.110.167809 · Cited by 49 · see citing works
Functions of acidic transmembrane residues in human melanocortin-3 receptor binding and activation
Shu-xiu, W., Fan, Z., & Tao, Y. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.05.026 · Cited by 46 · see citing works
Role of the brain melanocortins in blood pressure regulation
do Carmo, J. M., da Silva, A. A., Wang, Z., Fang, T., Aberdein, N., Perez de Lara, C. E., & Hall, J. E. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.03.003 · Cited by 38 · see citing works
Cardiovascular and renal actions of melanocyte-stimulating hormone peptides
Humphreys, M. H. (2006) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0b013e3280117fb5 · Cited by 36 · see citing works
Functions of the DRY motif and intracellular loop 2 of human melanocortin 3 receptor
Huang, H., & Tao, Y. (2014) · Journal of Molecular Endocrinology · doi:10.1530/jme-14-0184 · Cited by 36 · see citing works
Chapter 4 The Melanocortin‐1 Receptor Gene Polymorphism and Association with Human Skin Cancer
Beaumont, K. A., Liu, Y. Y., & Sturm, R. A. (2009) · Progress in molecular biology and translational science · doi:10.1016/s1877-1173(09)88004-6 · Cited by 35 · see citing works
Biphasic Effect of Melanocortin Agonists on Metabolic Rate and Body Temperature
Lute, B., Jou, W., Lateef, D. M., Goldgof, M., Xiao, C., Piñol, R. A., Kravitz, A. V., Miller, N., Huang, Y. G., Clemence, G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.021 · Cited by 35 · see citing works
Ni, X.-P., Bhargava, A., Pearce, D., & Humphreys, M. H. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00279.2005 · Cited by 34 · see citing works
Chalmers, J. A., Lin, S.-Y. J., Martino, T. A., Arab, S., Liu, P. X., Husain, M., Sole, M. J., & Belsham, D. D. (2008) · Journal of Molecular Endocrinology · doi:10.1677/jme-08-0050 · Cited by 32 · see citing works
Corander, M. P., Fenech, M., & Coll, A. P. (2009) · Circulation · doi:10.1161/circulationaha.109.854612 · Cited by 31 · see citing works
Altered islet prohormone processing: a cause or consequence of diabetes?
Ramzy, A., & Kieffer, T. J. (2021) · Physiological Reviews · doi:10.1152/physrev.00008.2021 · Cited by 27 · see citing works
Cardiovascular effects of melanocortins
Humphreys, M. H., Ni, X.-P., & Pearce, D. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.10.102 · Cited by 25 · see citing works
Tai, M.-H., Weng, W.-T., Lo, W.-C., Chan, J. Y. H., Lin, C.-J., Lam, H.-C., & Tseng, C.-J. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.118299 · Cited by 24 · see citing works
Anini, Y., Mayne, J., Gagnon, J., Sherbafi, J., Chen, A., Kaefer, N., Chrétien, M., & Mbikay, M. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.90 · Cited by 21 · see citing works
Neural and hormonal mechanisms of appetite regulation during eating
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Proneth, B., Pogozheva, I. D., Portillo, F. P., Mosberg, H. I., & Haskell‐Luevano, C. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800291b · Cited by 19 · see citing works
Chandramohan, G., Durham, N., Sinha, S. K., Norris, K. C., & Vaziri, N. D. (2009) · Metabolism · doi:10.1016/j.metabol.2009.04.022 · Cited by 19 · see citing works
Mouse Models of Human Proprotein Convertase Insufficiency
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Nyan, D., Anbazhagan, R., Hughes‐Darden, C., & Wachira, S. J. (2008) · Neuropeptides · doi:10.1016/j.npep.2007.12.007 · Cited by 17 · see citing works
Leptin in Association With Common Variants of MC3R Mediates Hypertension
Alsmadi, O. A., Melhem, M., Hebbar, P., Thareja, G., John, S. E., Alkayal, F., Behbehani, K., & Thanaraj, T. A. (2014) · American Journal of Hypertension · doi:10.1093/ajh/hpt285 · Cited by 16 · see citing works
Peter, J., Zipfel, G., Lecourt, A.-C., Bekel, A., & Hofbauer, K. G. (2010) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2010.534485 · Cited by 16 · see citing works
Activation and Endocytic Internalization of Melanocortin 3 Receptor in Neuronal Cells
Wachira, S. J., GURUSWAMY, B., Uradu, L., Hughes‐Darden, C., & Denaro, F. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1397.093 · Cited by 15 · see citing works
Role of melanocortin 4 receptor in hypertension induced by chronic intermittent hypoxia
do Carmo, J. M., da Silva, A. A., Moak, S. P., da Silva, F. S., Spradley, F. T., & Hall, J. E. (2018) · Acta Physiologica · doi:10.1111/apha.13222 · Cited by 14 · see citing works
Mayan, H., Ni, X.-P., Almog, S., & Humphreys, M. H. (2003) · Hypertension · doi:10.1161/01.hyp.0000097601.83235.f8 · Cited by 14 · see citing works
Langouche, L., Hersmus, N., Papageorgiou, A., Vankelecom, H. E. J., & Denef, C. (2004) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2004.01224.x · Cited by 13 · see citing works
The brain splits obesity and hypertension
Humphreys, M. H. (2011) · Nature Medicine · doi:10.1038/nm0711-782 · Cited by 12 · see citing works
A possible role for melanocortin peptides in longitudinal growth
Yeh, J. K., Evans, J. F., Niu, Q., & Aloia, J. F. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06729 · Cited by 11 · see citing works
Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions
Copperi, F., Kim, J. D., & Diano, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.725709 · Cited by 9 · see citing works
Zhan, S., Zhao, H.-B., White, A. J., Minami, M., Pignataro, G., Yang, T., Zhu, X., Lan, J., Xiong, Z., Steiner, D. F., et al. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2008.161 · Cited by 9 · see citing works
Prevention of Salt-Induced Hypertension by an Analog of γ-Melanocyte-Stimulating Hormone in the Rat
NI, X., & Humphreys, M. H. (2007) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2007.03.014 · Cited by 9 · see citing works
Yako, Y. Y., Fanampe, B. L., Hassan, S. M., Erasmus, R. T., van der Merwe, L., & Matsha, T. E. (2011) · PubMed · Cited by 9 · see citing works
Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity
Patel, T. P., Jun, J. Y., Seo, A. Y., Levi, N. J., Elizondo, D. M., Chen, J., Wong, A. M., Tugarinov, N., Altman, E. K., Gehle, D. B., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56936-1 · Cited by 8 · see citing works
β-Endorphin involvement in the regulatory response to body sodium overload
Caeiro, X. E., Hansen, C., Garcia, N. H., & Vivas, L. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.06.024 · Cited by 8 · see citing works
The natriuretic mechanism of Gamma-Melanocyte-Stimulating Hormone
Kathpalia, P. P., Charlton, C. A., Rajagopal, M., & Pao, A. C. (2011) · Peptides · doi:10.1016/j.peptides.2011.02.006 · Cited by 7 · see citing works
ACTH treatment promotes murine cardiac allograft acceptance
Zhao, J., Jiang, L., Uehara, M., Banouni, N., Dulaijan, B. S. A., Azzi, J. R., Ichimura, T., Li, X., Jarolı́m, P., Fiorina, P., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.143385 · Cited by 7 · see citing works
Wong, J., Nock, N. L., Xu, Z., Kyle, C., Daniels, A., White, M., Yue, D. K., Elston, R. C., & Mountjoy, K. G. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2007.11.002 · Cited by 7 · see citing works
Salt-sensitive hypertension: if only it were as simple as rocket science
Reudelhuber, T. L. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18397 · Cited by 7 · see citing works
Ni, X.-P., & Humphreys, M. H. (2008) · American Journal of Hypertension · doi:10.1038/ajh.2008.290 · Cited by 6 · see citing works
do Carmo, J. M., da Silva, A. A., Moak, S. P., Houghton, H. J., Smith, A. D., & Hall, J. E. (2015) · American Journal of Hypertension · doi:10.1093/ajh/hpv182 · Cited by 4 · see citing works
Cope, G., Flanagan, E., Houghton, B. L., Walsh, S. A., Johns, E. J., & Healy, V. (2012) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12025 · Cited by 3 · see citing works
Low, M. J. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-375097-6.10007-1 · Cited by 3 · see citing works
Cope, G., Kaushik, G., O’Sullivan, S., & Healy, V. (2013) · Peptides · doi:10.1016/j.peptides.2013.07.007 · Cited by 3 · see citing works
Ni, X.-P., van Dijk, C. M. A., Pearce, D., & Humphreys, M. H. (2009) · Experimental Physiology · doi:10.1113/expphysiol.2009.046748 · Cited by 3 · see citing works
Hypoxia inducible factor-dependent upregulation of Agrp in glomus type I cells of the carotid body
Mercado, L. L., Menendez-Montes, I., Tao, J., Chen, B., Olson, D. P., Mackaaij, C., Cleypool, C. G. J., & Gautron, L. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102095 · Cited by 2 · see citing works
Kolatkar, N. S., Thomas, A., & Williams, G. H. (2006) · Fundamental and clinical cardiology · doi:10.3109/9781420018905.002 · Cited by 2 · see citing works
Bełtowski, J. (2008) · Bioscience hypotheses · doi:10.1016/j.bihy.2008.07.007 · Cited by 1 · see citing works
Dietary salt intake matters for development of hypertension
Mullur, L. M. (2017) · BLDE University Journal of Health Sciences · doi:10.4103/bjhs.bjhs_12_17 · Cited by 1 · see citing works
Obesity and Stress: The Melanocortin Connection
Singhal, S., & Hill, J. W. (2018) · Springer eBooks · doi:10.1007/978-3-319-89506-2_11 · Cited by 1 · see citing works
Poritsanos, N. J. (2010) · Mspace (University of Manitoba)
NARRATIVE REVIEW Pathophysiological Mechanisms of Salt-Dependent Hypertension
Rodríguez‐Iturbe, B., Romero, F., & Johnson, R. J. (2007)
Pantel, J., Cone, R. D., & Stainbrook, S. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819460-7.00280-2
Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system
Hall, J. E., Omoto, A. C. M., do Carmo, J. M., da Silva, A. A., Mouton, A. J., Wang, Z., & Hall, M. E. (2026) · Clinical Science · doi:10.1042/cs20250039
- Authors
- Ni, X.-P., Pearce, D., Butler, A. A., Cone, R. D., & Humphreys, M. H.
- Affiliations
- San Francisco General Hospital (US)
- Oregon Health & Science University (US)
- Corresponding author
- Humphreys, Michael H.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-04-15
- Volume
- 111
- Issue
- 8
- Pages
- 1251-1258
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC152936
- OpenAlex
- W2027637340
- Cited by
- 74
- References
- 51
- Citations by year
- 2026: 1 · 2025: 3 · 2021: 4 · 2020: 1 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL068871, HL 68871)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK055819, R01DK051730, DK 58812, DK51730, DK 55819, DK-56695, R01DK058812, R01DK056695)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- gamma-MSH, salt-sensitive hypertension, PC2, sodium restriction, high-salt diet, mean arterial pressure, natriuretic peptides, alpha-melanocyte-stimulating hormone, central nervous system, gene disruption, mice
- MeSH terms
- Animals, Genotype, Hypertension, Mice, Inbred C57BL, Subtilisins, Sodium Chloride, Dietary, Receptors, Corticotropin, gamma-MSH, Receptor, Melanocortin, Type 3, Proprotein Convertase 2, Mice
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