Jeffrey L. Garvin, Ph.D.

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Biography

• B.S., Biology/Chemistry, University of Miami, Coral Gables, FL 1979
• Ph.D., Physiology, Duke University, Durham, NC 1984
• Fellow, Renal Physiology, NKF Fellowship, Lab. Kidney & Elect. Metabolism, NIH, Bethesda, MD 1984-1985
• Fellow Renal Physiology, NRSA, Lab. Kidney & Elect. Metabolism, NIH, Bethesda, MD 1985-1987

Summary of research interests:  Jeffrey L. Garvin, Ph.D.
At present we have three NIH-funded projects underway. The first deals with the regulation of a part of the nephron called the thick ascending limb function by nitric oxide (NO). We originally showed that NO produced by the thick ascending limb inhibits thick ascending limb transport. We then showed that endothelial NO synthase (eNOS) was the isoform involved using knockout mice and by developing a method for in vivo transduction of thick ascending limbs so that they express eNOS under the control of a thick ascending limb-specific promoter. While this technology had been used in other tissues, it had not been used successfully in vivo in the kidney. We also showed that NO reduced NaCl absorption less in thick ascending limbs from salt-sensitive rats than normotensive rats. We are now studying how luminal flow alters eNOS activity and its translocation from intracellular vesicles to the luminal membrane during activation. 
Our studies of NO led us to investigate the effects of superoxide on transport because superoxide scavenges NO, and has been reported to affect transporters in neurons. We first demonstrated that superoxide can stimulate NaCl absorption by any renal epithelium. We found that endogenously produced superoxide enhances NaCl absorption in the thick ascending limb primarily by increasing Na/K/2 Cl cotransport via activation of protein kinase C. We plan on pursuing this line of research by investigating the source of superoxide (probably NADPH oxidase) and the second messenger cascades activated by superoxide in greater detail.
Our studies of NO have led us to the conclusion that it is unlikely that NO simply diffuses through the lipid bilayer portion of cell membranes as is current dogma. Facilitated transport of NO seemed likely for a number of practical and thermodynamic reasons. We have shown that NO influx into proteoliposomes containing purified AQP-1 occurs 4 times faster than in liposomes not containing AQP-1. Similar results were also found for both transiently and stably transfected CHO-K1 cells. We are currently in the process of developing a grant on this topic.

Awards, Honors and Publications

Other Experience

• 1996-2007 Editorial Board; American Journal of Physiology: Renal Physiology
• 1996-1998 Editorial Board; Journal of the American Society of Nephrology
• 1997-2000 American Physiological Society Renal Section Program Committee
• 1997-2000 American Physiological Society Porter Physiology Development Committee
• 1997-2000 American Heart Association Council for High Blood Pressure Research Fall Conference Programming Committee
• 1998- Editorial Board; American Journal of Physiology: Reg., Int., and Comp.
• 2002 -2006 American Physiological Society Renal Section Steering Committee
• 2002 -2006 American Physiological Society Renal Section Treasurer
• 2002- Editorial Board; Hypertension
• 2003 National Institutes of Health CVB Study Section
• 2004-2007 National Institutes of Health HM Study Section
• 2007- Associate Editor; American Journal of Physiol: Renal Physiology

Honors

• 1984-1985 National Kidney Foundation Fellowship
• 1985-1987 National Research Service Award
• 1987-1988 National Research Service Award
• 1987 Lucille P. Markey Fellowship, Mt. Desert Island Biological Laboratory
• 2001- Fellow of the American Heart Association
• 2005 Lewis K. Dahl Lecture, American Heart Association

Selected Publications

• Ortiz, P.A., and J.L. Garvin. Autocrine effects of nitric oxide on HCO3- transport by rat thick ascending limb. Kidney Int. 58: 2069-2074, 2000.
• Garvin, J.L., and P.J. Harris. In vitro proximal tubule perfusion preparation. In: Methods in Molecular Medicine, ed. by D. Wang. Totowa, N.J.: Humana Press, 2000, pp. 451-470.
• Ren, Y., J.L. Garvin, and O.A. Carretero. Role of macula densa nitric oxide and cGMP in the regulation of tubuloglomerular feedback. Kidney Int. 58: 2053-2060, 2000.
• Ren, Y., J.L. Garvin, and O.A. Carretero. Efferent arteriole tubuloglomerular feedback in the renal nephron. Kidney Int. 59: 222-229, 2001.
• Ortiz, P.A., and J.L. Garvin. NO inhibits NaCl absorption by rat thick ascending limb through activation of cGMP-stimulated phosphodiesterase. Hypertension 37: 467-471, 2001.
• Boesch, D.M., and J.L. Garvin. Age-dependent activation of PKC isoforms by angiotensin II in the proximal nephron. Am. J. Physiol: Regul Integ Comp Physiol. 281: R861-R867, 2001.
• Plato, C.F., and J.L. Garvin. ?2-Adrenergic-mediated tubular NO production inhibits thick ascending limb chloride absorption. Am J Physiol: Renal Physiol. 281: F679-F686, 2001.
• Ortiz, P.A., and J.L. Garvin. Intrarenal transport and vasoactive substances in hypertension. Hypertension 38: 621-624, 2001.
• Ortiz, P.A., N.J. Hong, and J.L. Garvin. NO decreases thick ascending limb chloride absorption by reducing Na+-K+-2Cl- cotransporter activity. Am J Physiol: Renal Physiol 281: F819-F825, 2001.
• Ren, Y., J.L. Garvin, S. Ito, and O.A. Carretero. Role of neuronal nitric oxide synthase in the macula densa. Kidney Int. 60: 1676-1683, 2001.
• Wang, H., J.L. Garvin, and O.A. Carretero. Angiotensin II enhances tubuloglomerular feedback via luminal AT1 receptors on the macula densa. Kidney Int. 60: 1851-1857, 2001.
• Ren, Y., H. Yu, H. Wang, O.A. Carretero, and J.L. Garvin. Nystatin and valinomycin induce tubuloglomerular feedback. Am J Physiol: Renal Physiol. 281: F1102-F1108, 2001.
• Wang, H., O.A. Carretero, and J.L. Garvin. Nitric oxide produced by THAL nitric oxide synthase inhibits TGF. Hypertension 39: 662-666, 2002.
• Ren, Y., J.L. Garvin, and O.A. Carretero. Vasodilator action of angiotensin-(1-7) on isolated rabbit afferent arterioles. Hypertension 39: 799-802, 2002.
• Ren, Y., O.A. Carretero, and J.L. Garvin. Mechanism by which superoxide potentiates tubuloglomerular feedback. Hypertension 39: 624-628, 2002.
• Ortiz, P.A., and J.L. Garvin. Interaction of O2- and NO in the thick ascending limb. Hypertension 39: 591-596, 2002.
• Ortiz, P.A., and J.L. Garvin. Role of nitric oxide in the regulation of nephron transport. Am J Physiol: Renal Physiol. 282: F777-F784, 2002.
• Ren, Y., J. Garvin, and O.A. Carretero. Mechanism involved in bradykinin-induced efferent arteriole dilation. Kidney Int. 62: 544-549, 2002.
• Ren, Y., O.A. Carretero, and J.L. Garvin. Role of mesangial cells and gap junctions in tubuloglomerular feedback. Kidney Int. 62: 525-531, 2002.
• Rey, F.E., X.-C. Li, O.A. Carretero, J.L. Garvin, and P.J. Pagano. Perivascular superoxide anion contributes to impairment of endothelium-dependent relaxation. Role of gp91phox. Circulation 106: 2497-2502, 2002.
• Ortiz, P.A., and J.L. Garvin. Superoxide stimulates NaCl absorption by the thick ascending limb. Am J Physiol: Renal Physiol. 283: F957-F962, 2002.
• Ortiz, P.A., and J.L. Garvin. Cardiovascular and renal control in NOS-deficient mouse models. Am J Physiol: Regul Integ Comp Physiol. 284: R628-R638, 2003.
• Ortiz, P., B.A. Stoos, N.J. Hong, D.M. Boesch, C.F. Plato, and J.L. Garvin. High-salt diet increases sensitivity to NO and eNOS expression but not NO production in THALs. Hypertension 41: 682-687, 2003.
• Wang, H., O.A. Carretero, and J.L. Garvin. Inhibition of apical Na+/H+ exchangers on the macula densa cells augments tubuloglomerular feedback. Hypertension 41: 688-691, 2003.
• Ortiz, P.A., N.J. Hong, C.F. Plato, M. Varela, and J.L. Garvin. An in vivo method for adenovirus-mediated transduction of thick ascending limbs. Kidney Int. 63: 1141-1149, 2003.
• Ren, Y., J.L. Garvin, J.R. Falck, K.V. Renduchintala, and O.A. Carretero. Glomerular autacoids stimulated by bradykinin regulate efferent arteriole tone. Kidney Int. 63: 987-993, 2003.
• Ortiz, P.A., N.J. Hong, D. Wang, and J.L. Garvin. Gene transfer of eNOS to the thick ascending limb of eNOS-KO mice restores the effects of L-arginine on NaCl absorption. Hypertension 42: 674-679, 2003.
• Ren, Y., R. Liu, O.A. Carretero, and J.L. Garvin. Increased intracellular Ca++ in the macula densa regulates tubuloglomerular feedback. Kidney Int. 64: 1348-1355, 2003.
• Garvin, J.L., and P.A. Ortiz. The role of reactive oxygen species in the regulation of tubular function. Acta Physiol Scand. 179: 225-232, 2003.
• Ortiz, P.A., and J.L. Garvin. Trafficking and activation of eNOS in epithelial cells. Acta Physiol Scand. 179: 107-114, 2003.
• Varela, M., and J.L. Garvin. Acute and chronic regulation of thick ascending limb endothelial nitric oxide synthase by statins. J Am Soc Nephrol. 15: 269-275, 2004.
• Liu, R., Y. Ren, J.L. Garvin, and O.A. Carretero. Superoxide enhances tubuloglomerular feedback by constricting the afferent arteriole. Kidney Int. 66: 268-274, 2004.
• Ren, Y., J.L. Garvin, R. Liu, and O.A. Carretero. Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback. Kidney Int. 66: 1479-1485, 2004.
• Ortiz, P.A., N.J. Hong, and J.L. Garvin. Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. I. Am J Physiol: Renal Physiol. 287: F274-F280, 2004.
• Ortiz, P.A., N.L. Hong, and J.L. Garvin. Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90. Am J Physiol: Renal Physiol. 287: F281-F288, 2004.
• Varela, M., M. Herrera, and J.L. Garvin. Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2- and is diminished by a high-salt diet. Am J Physiol: Renal Physiol. 287: F224-F230, 2004.
• Herrera, M., and J.L. Garvin. Endothelin stimulates endothelial nitric oxide synthase expression in the thick ascending limb. Am J Physiol: Renal Physiol. 287: F231-F235, 2004.
• Ortiz, P.A., and J.L. Garvin. Nitric oxide (NO) modulation of Cl-dependent transporters in the kidney (Chapter 14). In: Cell Volume and Signaling. Advances in Experimental Medicine and Biology, Vol. 559, ed. by P.K. Lauf and N.C. Adragna. New York: Springer, 2004, pp. 147-156.
• Herrera, M., and J.L. Garvin. A high-salt diet stimulates thick ascending limb eNOS expression by raising medullary osmolality and increasing release of endothelin-1. Am J Physiol: Renal Physiol. 288: F58-F64, 2005.
• Martus, W., D. Kim, J.L. Garvin, and W.H. Beierwaltes. Commercial rodent diets contain more sodium than rats need. Am J Physiol: Renal Physiol. 288: F428-F431, 2005.
• Liu, R., O.A. Carretero, Y. Ren, and J.L. Garvin. Increased intracellular pH at the macula densa activates nNOS during tubuloglomerular feedback. Kidney Int. 67: 1837-1843, 2005.
• Herrera, M., and J.L. Garvin. Recent advances in the regulation of nitric oxide in the kidney. Hypertension 45: 1062-1067, 2005.
• Wang, H., J.L. Garvin, J.R. Falck, Y. Ren, S.S. Sankey, and O.A. Carretero. Glomerular cytochrome P-450 and cyclooxygenase metabolites regulate efferent arteriole resistance. Hypertension 46: 1175-1179, 2005.
• Juncos, R., and J.L. Garvin. Superoxide enhances Na-K-2Cl cotransporter activity in the thick ascending limb. Am J Physiol: Renal Physiol. 288: F982-F987, 2005.
• Garvin, J.L., and M. Herrera. Physiological actions of renal collecting duct endothelin. Am J Physiol: Renal Physiol. 288: F910-F911, 2005.
• Juncos, R., N.J. Hong, and J.L. Garvin. Differential effects of superoxide on luminal and basolateral Na+/H+ exchange in the thick ascending limb. Am J Physiol: Regul Integ Comp Physiol. 290: R79-R83, 2006.
• Herrera, M., G. Silva, and J.L. Garvin. A high-salt diet dissociates NO synthase-3 expression and NO production by the thick ascending limb. Hypertension 47: 95-101, 2006.
• Silva, G., W.H. Beierwaltes, and J.L. Garvin. Extracellular ATP stimulates NO production in rat thick ascending limb. Hypertension 47: 563-567, 2006.
• Zhuo, J.L., X.C. Li, J.L. Garvin, L.G. Navar, and O.A. Carretero. Intracellular ANG II induces cytosolic Ca2+ mobilization by stimulating intracellular AT1 receptors in proximal tubule cells. Am J Physiol: Renal Physiol. 290: F1382-F1390, 2006.
• Herrera, M., P.A. Ortiz, and J.L. Garvin. Regulation of thick ascending limb transport: role of nitric oxide. Am J Physiol: Renal Physiol. 290: F1279-F1284, 2006.
• Ortiz-Capisano, M.C., P.A. Ortiz, P. Harding, J.L. Garvin, and W.H. Beierwaltes. Decreased intracellular calcium stimulates cAMP and renin release. Hypertension 49: 162-169, 2007.
• Herrera, M., J.L. Garvin. Novel role of AQP-1 in NO dependent vasorelaxation. Am J Physiol: Renal Physiol. 292: F1442-F1451, 2007.
• Hong, N.J., J.L. Garvin. Flow increases superoxide production by NADPH oxidase via activation of Na/K/2Cl cotransport and mechanical stress in thick ascending limbs. Am J Physiol: Renal Physiol. 292(3): F993-F998, 2007.
• Liu, R., J.L. Garvin, Y.L. Ren, P.J. Pagano, and O.A. Carretero. Depolarization of the Macula Densa Induces Superoxide Production via NAD(P)H Oxidase. Am J Physiol: Renal Physiol. 292: 1867-1872, 2007.
• Ortiz-Capisano, M.C., Ortiz, P.A., Harding, P., Garvin, J.L., and W.H. Beierwaltes. Adenylyl cyclase isoform V mediates renin release from Juxtaglomerular cells. Hypertension 49: 618-624, 2007.
• Ortiz-Capisano, M.C., Ortiz, P.A., Garvin, J.L., Harding, P., and W.H. Beierwaltes. Expression and function of the calcium-sensing receptor in juxtaglomerular cells. Hypertension 50: 737-743, 2007
• Ren, Y., J.L. Garvin, R. Liu, and O.A. Carretero. Cross-talk between connecting tubule and afferent arteriole regulates renal microcirculation. Kidney Int. 71: 1116-1121, 2007.
• Ren, Y., J.L. Garvin, R. Liu, and O.A. Carretero. Possible Mechanism of Efferent Arteriole (Ef-Art) Tubuloglomerular feedback. Kidney Int. 71: 861-866, 2007.
• Garvin, J.L., and N.J. Hong. Cellular stretch increases superoxide production in the thick ascending limb. Hypertension. 51: 488-493, 2008.
• Ren, Y., D’Ambrosio, M.A., Wang, H., Liu, R., Garvin, J.L., and O.A. Carretero. Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF). Am J Physiol Renal Physiol. 295: 1207-1212, 2008.
• Silva, G.B., and J.L. Garvin. TRPV4 mediates hypotonicity-induced ATP release by the thick ascending limb. Am J Physiol Renal Physiol. 295: 1090-1095, 2008.
• Liu, R., Carretero, O.A., Ren, Y., Wang, H., and J.L. Garvin. Intracellular pH regulates superoxide production by the macula densa. Am J Physiol Renal Physiol. 295: 851-856, 2008.
• Ren, Y., Garvin, J.L., Liu, R., and O.A. Carretero. Cross-talk between arterioles and tubules in the kidney. Pediatr Nephrol. 24: 31-35, 2009.
• Ren Y., D'Ambrosio M.A., Garvin J.L., Wang H., and O.A. Carretero. Possible mediators of connecting tubule glomerular feedback. Hypertension 53: 319-323, 2009.
• Ramseyer V.D., and J.L. Garvin. Angiotensin II decreases nitric oxide synthase 3 expression via nitric oxide and superoxide in the thick ascending limb. Hypertension 53: 313-318, 2009.
• Perez-Rojas J, Kassem K, Beierwaltes WH, Garvin JL, Herrera M. "NO produced by endothelial NO synthase (NOS 3) promotes diuresis.  In Press,  Am J Physiol - Reg, Integ Comp Physiol., E-published ahead of print.2010
• Hong NJ, Silva GB, Garvin JL. PKC alpha mediates flow-stimulated superoxide production in thick ascending limbs. E-published ahead of print.Am J Physiol - Renal Physiol..2010.
• Silva GB, Garvin JL. Rac1 mediates NaCl-induced superoxide generation in the thick ascending limb. Am J Physiol - Renal Physiol. 298(2): E-published ahead of print. 2010