Michael Humphreys, MD
Professor Emeritus
Medicine
School of Medicine

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.

• Evidence for a noradrenergic mechanism causing hypertension and abnormal glucose metabolism in rats with relative deficiency of gamma-melanocyte-stimulating hormone.
  Experimental physiology 2009 Ni XP, van Dijk C, Pearce D, Humphreys MH
• Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.
  American journal of hypertension 2008 Ni XP, Humphreys MH
• Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat.
  American journal of hypertension 2007 Ni XP, Humphreys MH
• Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.
  Current opinion in nephrology and hypertension 2007 Humphreys MH
• Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones.
  Journal of hypertension 2006 Ni XP, Butler AA, Cone RD, Humphreys MH
• Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat.
  American journal of physiology. Renal physiology 2006 Knight S, Snellen H, Humphreys M, Baylis C
• Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney.
  American journal of physiology. Regulatory, integrative and comparative physiology 2005 Ni XP, Bhargava A, Pearce D, Humphreys MH
• 1,25 dihydroxyvitamin d amplifies type a natriuretic peptide receptor expression and activity in target cells.
  Journal of the American Society of Nephrology : JASN 2004 Chen S, Ni XP, Humphreys MH, Gardner DG
• Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.
  The American journal of clinical nutrition 2004 Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD
• Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat.
  Journal of the American Society of Nephrology : JASN 2004 Ni XP, Safai M, Rishi R, Baylis C, Humphreys MH
• Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients.
  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2004 Kalantar-Zadeh K, Kopple JD, Humphreys MH, Block G
• Gamma-MSH, sodium metabolism, and salt-sensitive hypertension.
  American journal of physiology. Regulatory, integrative and comparative physiology 2004 Humphreys MH
• A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients.
  Journal of the American Society of Nephrology : JASN 2004 Kalantar-Zadeh K, Block G, Humphreys MH, McAllister CJ, Kopple JD
• Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients.
  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2004 Kalantar-Zadeh K, Rodriguez RA, Humphreys MH
• Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat.
  Hypertension (Dallas, Tex. : 1979) 2003 Mayan H, Ni XP, Almog S, Humphreys MH
• Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse.
  The Journal of clinical investigation 2003 Ni XP, Pearce D, Butler AA, Cone RD, Humphreys MH
• Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients.
  Kidney international 2003 Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD
• Osmoregulation of endothelial nitric-oxide synthase gene expression in inner medullary collecting duct cells. Role in activation of the type A natriuretic peptide receptor.
  The Journal of biological chemistry 2002 Chen S, Cao L, Intengan HD, Humphreys M, Gardner DG
• Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis.
  Journal of the American Society of Nephrology : JASN 2001 Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH