Renal Vascular Physiology and Hypertension Lab

The general focus of the laboratory has been the role of the renal medullary microcirculation in normal physiology and the pathophysiology of hypertension.

A first line of investigation concerns the nature of microvascular transport as related to the countercurrent exchange that preserves high concentrations of sodium chloride and urea to facilitate urinary concentration.  Those efforts have defined the transport characteristics of the blood vessel (vasa recta) walls with respect to small solutes, water and macromolecules.  More recently, we have focused on cell to cell interactions in the vessel wall.  The endothelial layer of descending vasa recta was found to be an electrical syncytium that can transport large molecules between cells through communication channels called connexins.

A second area of emphasis has been the control of vasoactivity of descending vasa recta.  These vessels provide all blood flow to the kidney medulla, are 12 to 20 microns in diameter and are vasoactive; they constrict and dilate in response to various influences.  We have utilized imaging and electrophysiological methods to investigate membrane potential as a regulator of calcium entry as well as the 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. Learn more about Dr. Blaustein's research.

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 vasa recta endothelial nitric oxide generation.

Example Publications

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, 006.

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