Michael Humphreys, MD
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Title(s) | Professor Emeritus, Medicine |
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School | School of Medicine |
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Phone | 415-502-3834 |
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vCard | Download vCard |
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Biography University of California, San Francisco | Residency | | School of Medicine |
American Heart Association | 1999 | | John Alexander, MD Research Award | | 1991 | | Elected to American Clinical and Climatological Association | Case Western Reserve University | 1965 | | Alpha Omega Alpha Society |
Overview Dr. Humphreys' primary research interest has been in sodium metabolism and the pathophysiology of edema formation and salt-sensitive hypertension. He and his colleagues identified that rodent models of sodium retention like nephrotic syndrome, liver cirrhosis, and pregnancy are characterized by resistance to the natriuretic actions of atrial natriuretic peptide (ANP), and this in turn is caused by a heightened activity of Type V phosphodiesterase (PDE), which catabolizes cGMP formed normally in renal collecting duct cells when ANP interacts with its renal receptors. Inhibition of Type V PDE restores ANP responsiveness in these models. His group has also identified a novel hormonal system involved in normal sodium metabolism in rodents. It involves a peptide hormone gamma-melanocyte stimulating hormone (g-MSH) released from the pituitary ACTH precursor proopiomelanocortin. When animals are fed a high salt diet, g-MSH synthesis and secretion are up-regulated; it acts on the kidneys to increase sodium excretion, and on the brain to dampen down sympathetic excitation which occurs with high sodium intakes. When rodents have impaired ability to increase g-MSH secretion during ingestion of the high sodium diet, or lack the melanocortinr receptor with which it interacts, marked hypertension develops, and is accompanied by insulin resistance. Dr. Humphreys has also done clinical research in these areas and has studied the occurrence of HIV-associated nephropathy in patients at San Francisco General Hospital. He participated in early studies measuring nitrogen balance in ESRD patients treated with hemodialysis, and was for a short time a site director for the Frequent Hemodialysis Network clinical trial.
Research ORNG Applications Bibliographic
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Humphreys MH. Renal nerves and CKD: is renal denervation the answer? J Am Soc Nephrol. 2012 Jul; 23(7):1132-5. PMID: 22677558.
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Humphreys MH. The brain splits obesity and hypertension. Nat Med. 2011 Jul 07; 17(7):782-3. PMID: 21738154.
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Humphreys MH, Ni XP, Pearce D. Cardiovascular effects of melanocortins. Eur J Pharmacol. 2011 Jun 11; 660(1):43-52. PMID: 21199648; PMCID: PMC3086937.
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Sasser JM, Ni XP, Humphreys MH, Baylis C. Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat. Am J Physiol Renal Physiol. 2010 Oct; 299(4):F810-4. PMID: 20668100; PMCID: PMC2957261.
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Chen S, Grigsby CL, Law CS, Ni X, Nekrep N, Olsen K, Humphreys MH, Gardner DG. Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents. J Clin Invest. 2009 Jun; 119(6):1647-58. PMID: 19436108; PMCID: PMC2689130.
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Ni XP, van Dijk C, Pearce D, Humphreys MH. Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone. Exp Physiol. 2009 Aug; 94(8):867-76. PMID: 19429645; PMCID: PMC2853237.
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Ni XP, Humphreys MH. Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet. Am J Hypertens. 2008 Dec; 21(12):1284-7. PMID: 18802429; PMCID: PMC3035849.
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Ni XP, Humphreys MH. Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat. Am J Hypertens. 2007 Aug; 20(8):862-5. PMID: 17679034.
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Humphreys MH. Cardiovascular and renal actions of melanocyte-stimulating hormone peptides. Curr Opin Nephrol Hypertens. 2007 Jan; 16(1):32-8. PMID: 17143069.
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Ni XP, Butler AA, Cone RD, Humphreys MH. Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones. J Hypertens. 2006 Nov; 24(11):2239-46. PMID: 17053546.
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Knight S, Snellen H, Humphreys M, Baylis C. Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat. Am J Physiol Renal Physiol. 2007 Feb; 292(2):F655-9. PMID: 17003222; PMCID: PMC2765210.
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Ni XP, Bhargava A, Pearce D, Humphreys MH. Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney. Am J Physiol Regul Integr Comp Physiol. 2006 Mar; 290(3):R560-7. PMID: 16195498.
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Chen S, Ni XP, Humphreys MH, Gardner DG. 1,25 dihydroxyvitamin d amplifies type a natriuretic peptide receptor expression and activity in target cells. J Am Soc Nephrol. 2005 Feb; 16(2):329-39. PMID: 15590756.
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Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr. 2004 Aug; 80(2):299-307. PMID: 15277149.
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Ni XP, Safai M, Rishi R, Baylis C, Humphreys MH. Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat. J Am Soc Nephrol. 2004 May; 15(5):1254-60. PMID: 15100365; PMCID: PMC2756797.
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Kalantar-Zadeh K, Kopple JD, Humphreys MH, Block G. Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients. Nephrol Dial Transplant. 2004 Jun; 19(6):1507-19. PMID: 15069177.
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Humphreys MH. Gamma-MSH, sodium metabolism, and salt-sensitive hypertension. Am J Physiol Regul Integr Comp Physiol. 2004 Mar; 286(3):R417-30. PMID: 14761863.
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Kalantar-Zadeh K, Block G, Humphreys MH, McAllister CJ, Kopple JD. A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients. J Am Soc Nephrol. 2004 Feb; 15(2):442-53. PMID: 14747392.
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Kalantar-Zadeh K, Rodriguez RA, Humphreys MH. Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant. 2004 Jan; 19(1):141-9. PMID: 14671049.
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Mayan H, Ni XP, Almog S, Humphreys MH. Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat. Hypertension. 2003 Nov; 42(5):962-7. PMID: 14568996.
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Ni XP, Pearce D, Butler AA, Cone RD, Humphreys MH. Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest. 2003 Apr; 111(8):1251-8. PMID: 12697744; PMCID: PMC152936.
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Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003 Mar; 63(3):793-808. PMID: 12631061.
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Chen S, Cao L, Intengan HD, Humphreys M, Gardner DG. Osmoregulation of endothelial nitric-oxide synthase gene expression in inner medullary collecting duct cells. Role in activation of the type A natriuretic peptide receptor. J Biol Chem. 2002 Sep 06; 277(36):32498-504. PMID: 12082097.
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