Dr. Thomas Pallone is Professor of Medicine in the Division of Nephrology. He received the medical degree at Pennsylvania State University followed by Internal Medicine residency training at the University of Maryland, Nephrology fellowship training at Stanford University and additional research training in the Medical Engineering Medical Sciences division of the HST program at the Massachusetts Institute of Technology.
Research in my laboratory involves study of the physiology of renal medullary microcirculation. There have been three foci.
The first line of investigation has been microvascular transport by the medullary microcirculation. That area addresses countercurrent exchange in the renal medulla relevant to the urinary concentrating mechanism. Ongoing studies in this area are now focused on transport processes between cells of the vessels wall through connexins. We have found that the endothelial layer is an electrical syncytium that is capable of transporting large molecules between cells along the vessel axis. The latter is relevant to microvascular contraction and endothelium dependent vasodilator functions.
A second area of emphasis has been the control of vasoactivity of descending vasa recta ~12 to 20 micron diameter microvessels that supply all blood flow to the renal medulla. Areas of study include the role of membrane potential as a regulator of calcium entry into smooth muscle / pericytes and endothelial cells and the ion channel architecture that controls it. We have studied the role of reactive oxygen species and oxidative stress in the regulation of vasoactivity in both health and hypertension.
A third area of investigation control of renal medullary perfusion and renal microvessel function by cardiac glycosides such as ouabain. That topic has been pursued in collaboration with investigators in the Department of Physiology, headed by Dr. Mordecai Blaustein. Our investigations have shown that ouabain modulates Ca2+ signaling and nitric oxide generation by the endothelium. We have found that chronic ouabain elevation induces hypertension and leads to diminution of endothelial nitric oxide generation.
Pallone T. Is oxidative stress differentially regulated in the renal cortex and medulla? Nature Clinical Practice Nephrology. 2: 118-119, 2006
Cao C, Goo JH, Lee-Kwon W, Pallone TL. Descending Vasa Recta Pericytes Express an Inward Rectifier K+ Conductance. Am. J Physiol. Regul Integrative Physiol 290:R1601-1607, 2006.
Pittner J, Rhinehart K, Pallone TL. Ouabain modulation of endothelial calcium signaling in descending vasa recta. Am J Physiol Renal Physiol 291: F761-F769, 2006.
Zhang Q, Cao C, Mangano M, Zhang Z, Silldorff EP, Lee-Kwon W, Pallone TL. Descending vasa recta endothelium is an electrical syncytium. Am J Physiol Regulatory Integrative Physiol. 291: R1688-R1699, 2006.
Lee-Kwon W, Goo JH, Zhang Z, Silldorff EP, Pallone TL. Vasa recta voltage gated Na+ channel NaV1.3 is regulated by calmodulin. Am J Physiol Renal Physiol 292:F404-F414, 2007.
Pallone T. Control of Renal Na+ Excretion by Heme Oxygenase. Hypertension. 49: 23-24, 2007.
Edwards AE, Pallone TL. Modification of cytoplasmic calcium signaling by subplasmalemmal microdomains. Am J Physiol Renal Physiol 292: F1827-F1845, 2007.
Cao C, Lee-Kwon W, Payne K, Edwards AE, Pallone TL. Descending vasa recta endothelia express inward rectifier potassium channels. Am J Physiol Renal Physiol 293: F1248-F1255, 2007.
Pallone TL. Aquaporin 1, urea transporters and renal vascular bundles. J Am Soc Nephrol. 18: 2798-2800, 2007.
Pallone TL, Cao C. Renal Cortical and Medullary Microcirculations: Structure and Function. In: The Kidney: Physiology and Pathophysiology. 4rd edition. pp 627-670, Eds. Alpern C. and Hebert S. Elsevier Press, San Diego, CA, 2007
Navar LG, Arendshorst WJ, Pallone TL, Inscho EW, Imig JD, Bell PD. The Renal Microcirculation, Part V, Chpt 13, Handbook of Physiology, pp. 550-683, eds: Tuma RF, Duran, WN, Ley K. American Physiological Society Press, 2008.
Edwards A, Pallone TL. Mechanisms underlying angiotensin II induced calcium oscillations. Am J Physiol Renal Physiol 295: F568-F584, 2008.
Cao C, Payne K, Lee-Kwon W, Zhang Z, Lim SW, Hamlyn J, Kwon HM, Blaustein MP, Pallone TL. Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat. Am J Physiol Renal Physiol Am J Physiol Renal Physiol 296: F98-F106, 2009.
Sendeski M, Patzak A, Pallone TL, Cao C, Persson AE, Persson PB. Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy. Radiology 251:697-704, 2009.
Raina H, Zhang Q, Rhee AY, Pallone TL, Wier WG. Sympathetic nerves and the endothelium influence the vasoconstrictor effect of low concentrations of ouabain in pressurized small arteries. Am J Physiol Heart Circ Physiol. 298(6):H2093-101, 2010. Epub 2010 Apr 9. PMID: 20382851
Zhang Z, Lin H, Cao C, Khurana S, Pallone TL. Voltage gated divalent currents in descending vasa recta pericytes. Am J Physiol Renal Physiol. 299(4):F862-71, 2010 PMID: 20630935
Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai CY, Patzak A, Pallone TL. Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction. Am J Physiol Renal Physiol. 299(5):F1056-64, 2010 PMID: 20702600
Edwards A, Cao C, Pallone TL. Cellular mechanisms underlying nitric oxide-induced vasodilation of descending vasa recta. Am J Physiol Renal Physiol. 2011 Feb;300(2):F441-56. PMID: 21084408; PMCID: PMC3044008.
Blaustein MP, Leenen FH, Chen L, Golovina VA, Hamlyn JM, Pallone TL, Van Huysse JW, Zhang J, Wier WG. How NaCl raises blood pressure: A new paradigm for the pathogenesis of salt-dependent hypertension. Am J Physiol Heart Circ Physiol. 2012 02:H1031-49.
Sandeep Khurana, Hema Raina, Valeria Pappas, Jean-Pierre Raufman, Thomas L Pallone. Effects of Deoxycholylglycine, a Conjugated Secondary Bile Acid, on Myogenic Tone and Agonist-Induced Contraction in Rat Resistance Arteries PLoS ONE 2012;7(2):e32006
Thomas L. Pallone, Aurélie Edwards, David L. Mattson. Renal Medullary Circulation. Compr Physiol 2012, 2: 97-140. doi: 10.1002/cphy.c100036
Pallone TL, Khurana S, and C Cao. Calcium channels: voltage gated structure and function (CACNA). Encyclopedia of signaling molecules. Part 23 pp 1984-1992. 2012 Springer Verlag. S Choi editor