Vanderbilt University School of Medicine

Brown, Nancy J. , M.D.
Chair of the Department of Medicine
Professor of Medicine
Hugh J. Morgan Chair in Medicine
Professor of Pharmacology

Lab Url: N/A

Phone Number: 615-343-8701


Brown, Nancy's picture

Office Address   Mailing Address

D-3100 Medical Center North

D-3100 Medical Center North

Research Description
Research in our laboratory focuses on the following areas:
1. Role of the renin-angiotensin-aldosterone system in modulating oxidative stress, inflammation and fibrinolysis.
The renin-angiotensin-aldosterone system (RAAS) is one of the major blood pressure regulating systems in the body. The small peptide angiotensin II, Ang II, raises blood pressure by constricting blood vessels and increasing salt retention, in part by stimulating synthesis of the mineralocorticoid aldosterone. We now understand that the RAAS has other detrimental effects on the blood vessels, heart and kidney. Both Ang II and aldosterone cause inflammation and fibrosis and promote clotting. Studies in our laboratory are examining the mechanisms of these effects.

2. Role of the renin-angiotensin-aldosterone system in regulating glucose homeostasis.
Sixty per cent of Americans are obese and both the activity of the RAAS and inflammation are increased in obesity. Obese individuals are at increased risk for the development of diabetes and hypertension, but drugs that interrupt the RAAS seem to decrease this risk. Studies in our laboratory are helping us to understand the mechanism for this effect so that we may devise better strategies to prevent diabetes.

3. Cardiovascular effects of the kallikrein-kinin system.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the two major classes of drugs currently used to interrupt the renin-angiotensin-aldosterone system. ACE inhibitors decrease the formation of Ang II, whereas ARBs block the effect of Ang II at its major receptor. In addition, ACE inhibitors prevent the breakdown of and promote the actions of bradykinin, a peptide in the body that lowers blood pressure. Bradykinin has other beneficial effects, like increasing tissue-type plasminogen activator from the endothelium. Bradykinin can also have detrimental effects, promoting inflammation. The net beneficial or detrimental effect of bradykinin may depend on the health of the blood vessels.

4. Role of arachidonic acid monooxygenases and epoxygenases in the regulation of blood pressure and cardiovascular risk.
Bradykinin exerts its blood pressure lowering effects, in part, through effects on cytochrome P450 (CYP450) epoxygenases that form eicosatetraenoic acids (EETs) from arachidonic acid. EETs relax blood vessels. EETs formed in the kidney also stimulate salt excretion. Animal studies suggest that, in the kidney, EET formation is regulated in part by 20-hydroxyeicosatetraenoic acid 20-HETE, the product of CYP4A11. Research in our laboratory indicates that a loss-of-function variant of the gene encoding CYP4A11 is associated with high blood pressure and progression of renal disease. We are refining our understanding of how these systems regulate blood pressure in humans and how they interact with the RAAS.

5. Contribution of peptidases to angiotensin-converting enzyme (ACE) inhibitor-associated angioedema.
Despite the many beneficial effects of ACE inhibitors, this class of medications can cause swelling of the lips, tongue, or face, a side effect called angioedema. Likely, this side effect results from decreased breakdown of bradykinin and another peptide called substance P. We have determined groups of patients who are at increased risk for angioedema. Studies in our laboratory have identified one pathway involved in angioedema and will allow us to better predict risk and prevent the side effect.

6. Pharmacogenetics of the renin-angiotensin-aldosterone and kallikrein-kinin sytems.
Genetic factors modulate all of the processes described above. One goal of our laboratory is to identify these factors in order to better predict individual responses to drugs such as ACE inhibitors, ARBs, aldosterone receptor blockers and renin inhibitors.

Clinical Interests

Balaguer, JM, Yu, C, Byrne, JG, Ball, SK, Petracek, MR, Brown, NJ, Pretorius, M. Contribution of endogenous bradykinin to fibrinolysis, inflammation, and blood product transfusion following cardiac surgery: a randomized clinical trial. Clin Pharmacol Ther, 93(4), 326-34, 2013.

Brown, NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol, 9(8), 459-69, 2013.

Brown, NJ. Developing physician-scientists: a perspective. Trans Am Clin Climatol Assoc, 124, 218-29, 2013.

Dias, E, Hachey, B, McNaughton, C, Nian, H, Yu, C, Straka, B, Brown, NJ, Caprioli, RM. An LC-MS assay for the screening of cardiovascular medications in human samples. J Chromatogr B Analyt Technol Biomed Life Sci, 937, 44-53, 2013.

Gilbert, K, Nian, H, Yu, C, Luther, JM, Brown, NJ. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension. J Hypertens, 31(4), 820-9, 2013.

Theobald, CN, Stover, DG, Choma, NN, Hathaway, J, Green, JK, Peterson, NB, Sponsler, KC, Vasilevskis, EE, Kripalani, S, Sergent, J, Brown, NJ, Denny, JC. The effect of reducing maximum shift lengths to 16 hours on internal medicine interns'' educational opportunities. Acad Med, 88(4), 512-8, 2013.

Ayers, K, Byrne, LM, DeMatteo, A, Brown, NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension, 59(4), 893-8, 2012.

Billings, FT, Balaguer, JM, C, Y, Wright, P, Petracek, MR, Byrne, JG, Brown, NJ, Pretorius, M. Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass. Clin Pharmacol Ther, 91(6), 1065-73, 2012.

Billings, FT, Pretorius, M, Schildcrout, JS, Mercaldo, ND, Byrne, JG, Ikizler, TA, Brown, NJ. Obesity and oxidative stress predict AKI after cardiac surgery. J Am Soc Nephrol, 23(7), 1221-8, 2012.

Brown, NJ. Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies. J Am Soc Hypertens, 6(3), 163-8, 2012.

Brown, NJ. Patient-oriented research in the era of personalized medicine. Clin Transl Sci, 5(2), 119-20, 2012.

Delaney, JT, Jeff, JM, Brown, NJ, Pretorius, M, Okafor, HE, Darbar, D, Roden, DM, Crawford, DC. Characterization of genome-wide association-identified variants for atrial fibrillation in African Americans. PLoS One, 7(2), e32338, 2012.

Gamboa, JL, Pretorius, M, Todd-Tzanetos, DR, Luther, JM, Yu, C, Ikizler, TA, Brown, NJ. Comparative effects of angiotensin-converting enzyme inhibition and angiotensin-receptor blockade on inflammation during hemodialysis. J Am Soc Nephrol, 23(2), 334-42, 2012.

Luther, JM, Luo, P, Wang, Z, Cohen, SE, Kim, HS, Fogo, AB, Brown, NJ. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II-induced cardiac, renal, and vascular injury. Kidney Int, 82(6), 643-51, 2012.

Pretorius, M, Murray, KT, Yu, C, Byrne, JG, Billings, FT, Petracek, MR, Greelish, JP, Hoff, SJ, Ball, SK, Mishra, V, Body, SC, Brown, NJ. Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery. Crit Care Med, 40(10), 2805-12, 2012.

Darbar, M, Emans, SJ, Harris, ZL, Brown, NJ, Scott, TA, Cooper, WO. Part-time physician faculty in a pediatrics department: a study of equity in compensation and academic advancement. Acad Med, 86(8), 968-73, 2011.

Lee, CR, Pretorius, M, Schuck, RN, Burch, LH, Bartlett, J, Williams, SM, Zeldin, DC, Brown, NJ. Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans. Hypertension, 57(1), 116-22, 2011.

Luther, JM, Brown, NJ. The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol Sci, 32(12), 734-9, 2011.

Luther, JM, Luo, P, Kreger, MT, Brissova, M, Dai, C, Whitfield, TT, Kim, HS, Wasserman, DH, Powers, AC, Brown, NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia, 54(8), 2152-63, 2011.

Billings, FT, Pretorius, M, Siew, ED, Yu, C, Brown, NJ. Early postoperative statin therapy is associated with a lower incidence of acute kidney injury after cardiac surgery. J Cardiothorac Vasc Anesth, 24(6), 913-20, 2010.

Brown, NJ. Therapeutic potential of plasminogen activator inhibitor-1 inhibitors. Ther Adv Cardiovasc Dis, 4(5), 315-24, 2010.

Byrd, JB, Woodard-Grice, A, Stone, E, Lucisano, A, Schaefer, H, Yu, C, Eyler, AE, Salloum, NE, Brown, NJ. Association of angiotensin-converting enzyme inhibitor-associated angioedema with transplant and immunosuppressant use. Allergy, 65(11), 1381-7, 2010.

Fong, P, Stafforini, DM, Brown, NJ, Pretorius, M. Increased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism. Free Radic Biol Med, 49(2), 301-5, 2010.

Garg, R, Williams, GH, Hurwitz, S, Brown, NJ, Hopkins, PN, Adler, GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism, , , 2010.

Gilbert, KC, Brown, NJ. Aldosterone and inflammation. Curr Opin Endocrinol Diabetes Obes, 17(3), 199-204, 2010.

Pretorius, M, Brown, NJ. Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but attenuates vascular tissue-type plasminogen activator release. J Pharmacol Exp Ther, 332(1), 291-7, 2010.

Saxena, AR, Karumanchi, SA, Brown, NJ, Royle, CM, McElrath, TF, Seely, EW. Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. Hypertension, 55(5), 1239-45, 2010.

Underwood, PC, Sun, B, Williams, JS, Pojoga, LH, Chamarthi, B, Lasky-Su, J, Raby, BA, Hopkins, PN, Jeunemaitre, X, Brown, NJ, Adler, GK, Williams, GH. The relationship between peroxisome proliferator-activated receptor-gamma and renin: a human genetics study. J Clin Endocrinol Metab, 95(9), E75-9, 2010.

Woodard-Grice, AV, Lucisano, AC, Byrd, JB, Stone, ER, Simmons, WH, Brown, NJ. Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema. Pharmacogenet Genomics, 20(9), 532-6, 2010.

Body, SC, Collard, CD, Shernan, SK, Fox, AA, Liu, KY, Ritchie, MD, Perry, TE, Muehlschlegel, JD, Aranki, S, Donahue, BS, Pretorius, M, Estrada, JC, Ellinor, PT, Newton-Cheh, C, Seidman, CE, Seidman, JG, Herman, DS, Lichtner, P, Meitinger, T, Pfeufer, A, K????b, S, Brown, NJ, Roden, DM, Darbar, D. Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery. Circ Cardiovasc Genet, 2(5), 499-506, 2009. PMCID:2801871

Brown, NJ, Byiers, S, Carr, D, Maldonado, M, Warner, BA. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension, 54(3), 516-23, 2009. PMCID:2758288

Hill, KD, Eckhauser, AW, Marney, A, Brown, NJ. Phosphodiesterase 5 inhibition improves beta-cell function in metabolic syndrome. Diabetes Care, 32(5), 857-9, 2009. PMCID:2671107

Lea, WB, Kwak, ES, Luther, JM, Fowler, SM, Wang, Z, Ma, J, Fogo, AB, Brown, NJ. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney Int, 75(9), 936-44, 2009.

Luther, JM, Wang, Z, Ma, J, Makhanova, N, Kim, HS, Brown, NJ. Endogenous aldosterone contributes to acute Ang II-stimulated PAI-1 and ppET-1 expression in heart but not aorta. Endocrinology, 150, 2229-2236, 2009. PMCID:2671907

Marney, AM, Ma, J, Luther, JM, Ikizler, TA, Brown, NJ. Endogenous bradykinin contributes to increased plasminogen activator inhibitor 1 antigen following hemodialysis. J Am Soc Nephrol, 20(10), 2246-52, 2009. PMCID:2754101

Brown, AM, Morrow, JD, Limbird, LE, Byrne, DW, Gabbe, SG, Balser, JR, Brown, NJ. Centralized oversight of physician-scientist faculty development at Vanderbilt: early outcomes. Acad Med, 83(10), 969-75, 2008.

Brown, NJ. Aldosterone and vascular inflammation. Hypertension, 51(2), 161-7, 2008.

Byrd, JB, Touzin, K, Sile, S, Gainer, JV, Yu, C, Nadeau, J, Adam, A, Brown, NJ. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension, 51(1), 141-7, 2008. PMCID:2749928

Fleming, GA, Murray, KT, Yu, C, Byrne, JG, Greelish, JP, Petracek, MR, Hoff, SJ, Ball, SK, Brown, NJ, Pretorius, M. Milrinone use is associated with postoperative atrial fibrillation after cardiac surgery. Circulation, 118(16), 1619-25, 2008.

Gainer, JV, Lipkowitz, MS, Yu, C, Waterman, MR, Dawson, EP, Capdevila, JH, Brown, NJ, , . Association of a CYP4A11 variant and blood pressure in black men. J Am Soc Nephrol, 19(8), 1606-12, 2008. PMCID:2488260

Pretorius, M, van Guilder, GP, Guzman, RJ, Luther, JM, Brown, NJ. 17{beta}-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women. Hypertension, 51, 1190-1196, 2008. PMCID:2673569

Pretorius, MM, Gainer, JV, Van Guilder, GP, Coelho, EB, Luther, JM, Fong, P, Rosenbaum, DD, Malave, HA, Yu, C, Ritchie, MD, Vaughan, DE, Brown, NJ. The bradykinin type 2 receptor BE1 polymorphism and ethnicity influence systolic blood pressure and vascular resistance. Clin Pharmacol Ther, 83(1), 122-9, 2008.

Schoenhard, JA, Asselbergs, FW, Poku, KA, Stocki, SA, Gordon, S, Vaughan, DE, Brown, NJ, Moore, JH, Williams, SM. Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. Hum Genet, , 479-88, 2008.

Van Guilder, GP, Pretorius, M, Luther, JM, Byrd, JB, Hill, K, Gainer, JV, Brown, NJ. Bradykinin type 2 receptor BE1 genotype influences bradykinin-dependent vasodilation during angiotensin-converting enzyme inhibition. Hypertension, 51(2), 454-9, 2008. PMCID:2581632

Brown, NJ, Bradford, J, Wang, Z, Lea, W, Ma, L, Ma, J, Vaughan, DE, Fogo, AB. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney Int, 72(1), 72-81, 2007.

Byrd, JB, Shreevatsa, A, Putlur, P, Foretia, D, McAlexander, L, Sinha, T, Does, MD, Brown, NJ. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol, 120(2), 403-8, 2007.

Chamarthi, B, Kolatkar, NS, Hunt, SC, Williams, JS, Seely, EW, Brown, NJ, Murphey, LJ, Jeunemaitre, X, Williams, GH. Urinary Free Cortisol: An Intermediate Phenotype And A Potential Genetic Marker For A Salt-Resistant Subset Of Essential Hypertension. J Clin Endocrinol Metab, 92, 1340-1346, 2007.

Gumieniak, O, Perlstein, TS, Williams, JS, Hopkins, PN, Brown, NJ, Raby, BA, Williams, GH. Ala92 Type 2 Deiodinase Allele Increases Risk for the Development of Hypertension. Hypertension, 49, 461-466, 2007.

Lefebvre, J, Shintani, A, Gebretsadik, T, Petro, JR, Murphey, LJ, Brown, NJ. Bradykinin B2 Receptor Does Not Contribute to Blood Pressure Lowering During AT1 Receptor Blockade. J Pharmacol Exp Ther, 320, 1261-1267, 2007. PMCID:2673724

Marney, AM, Brown, NJ. Aldosterone and end-organ damage. Clin Sci (Lond), 113(6), 267-78, 2007.

Muldowney, JA, Painter, CA, Sanders-Bush, E, Brown, NJ, Vaughan, DE. Acute tissue-type plasminogen activator release in human microvascular endothelial cells: The roles of Galpha(q), PLC-beta, IP(3) and 5,6-epoxyeicosatrienoic acid. Thromb Haemost, 97(2), 263-71, 2007.

Pretorius, M, Donahue, BS, Yu, C, Greelish, JP, Roden, DM, Brown, NJ. Plasminogen activator inhibitor-1 as a predictor of postoperative atrial fibrillation after cardiopulmonary bypass. Circulation, 116(11 Suppl), I1-7, 2007.

Sile, S, Gillani, NB, Velez, DR, Vanoye, CG, Yu, C, Byrne, LM, Gainer, JV, Brown, NJ, Williams, SM, George, AL. Functional BSND variants in essential hypertension. Am J Hypertens, 20(11), 1176-1182, 2007.

Williams, SM, Stocki, S, Jiang, L, Brew, K, Gordon, S, Vaughan, DE, Brown, NJ, Poku, KA, Moore, JH. A population-based study in Ghana to investigate inter-individual variation in plasma t-PA and PAI-1. Ethn Dis, 17(3), 492-7, 2007.

Brown, NJ. Blood Pressure Reduction and Tissue-Type Plasminogen Activator Release. Hypertension, 47, 648-649, 2006.

Brown, NJ, Muldowney, JA, Vaughan, DE. Endogenous NO regulates plasminogen activator inhibitor-1 during angiotensin-converting enzyme inhibition. Hypertension, 47(3), 441-8, 2006.

Byrd, JB, Adam, A, Brown, NJ. Angiotensin-converting enzyme inhibitor-associated angioedema. Immunol Allergy Clin North Am, 26(4), 725-37, 2006.

Luther, JM, Gainer, JV, Murphey, LJ, Yu, C, Vaughan, DE, Morrow, JD, Brown, NJ. Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism. Hypertension, 48(6), 1050-7, 2006.

Ma, J, Weisberg, A, Griffin, JP, Vaughan, DE, Fogo, AB, Brown, NJ. Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury. Kidney Int, 69(6), 1064-72, 2006.

Motsinger, AA, Donahue, BS, Brown, NJ, Roden, DM, Ritchie, MD. Risk factor interactions and genetic effects associated with post-operative atrial fibrillation. Pac Symp Biocomput, , 584-95, 2006.

Murphey, LJ, Malave, HA, Petro, J, Biaggioni, I, Byrne, DW, Vaughan, DE, Luther, JM, Pretorius, M, Brown, NJ. Bradykinin and its metabolite bradykinin 1-5 inhibit thrombin-induced platelet aggregation in humans. J Pharmacol Exp Ther, 318(3), 1287-92, 2006.

Pojoga, L, Kolatkar, NS, Williams, JS, Perlstein, TS, Jeunemaitre, X, Brown, NJ, Hopkins, PN, Raby, BA, Williams, GH. Beta-2 adrenergic receptor diplotype defines a subset of salt-sensitive hypertension. Hypertension, 48(5), 892-900, 2006. PMCID:2801871

Williams, JS, Williams, GH, Raji, A, Jeunemaitre, X, Brown, NJ, Hopkins, PN, Conlin, PR. Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia. J Hum Hypertens, 20(2), 129-36, 2006.

Aldigier, JC, Kanjanbuch, T, Ma, LJ, Brown, NJ, Fogo, AB. Regression of existing glomerulosclerosis by inhibition of aldosterone. J Am Soc Nephrol, 16(11), 3306-14, 2005.

Brown, NJ. Aldosterone and end-organ damage. Curr Opin Nephrol Hypertens, 14(3), 235-41, 2005.

Gainer, JV, Bellamine, A, Dawson, EP, Womble, KE, Grant, SW, Wang, Y, Cupples, LA, Guo, CY, Demissie, S, O'Donnell, CJ, Brown, NJ, Waterman, MR, Capdevila, JH. Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation, 111(1), 63-9, 2005.

Ma, J, Albornoz, F, Yu, C, Byrne, DW, Vaughan, DE, Brown, NJ. Differing effects of mineralocorticoid receptor-dependent and -independent potassium-sparing diuretics on fibrinolytic balance. Hypertension, 46(2), 313-20, 2005.

Pretorius, M, Luther, JM, Murphey, LJ, Vaughan, DE, Brown, NJ. Angiotensin-converting enzyme inhibition increases basal vascular tissue plasminogen activator release in women but not in men. Arterioscler Thromb Vasc Biol, 25(11), 2435-40, 2005.

Pretorius, M, Scholl, FG, McFarlane, JA, Murphey, LJ, Brown, NJ. A pilot study indicating that bradykinin B2 receptor antagonism attenuates protamine-related hypotension after cardiopulmonary bypass. Clin Pharmacol Ther, 78(5), 477-85, 2005.

Weisberg, AD, Albornoz, F, Griffin, JP, Crandall, DL, Elokdah, H, Fogo, AB, Vaughan, DE, Brown, NJ. Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling. Arterioscler Thromb Vasc Biol, 25(2), 365-71, 2005.

Xu, BJ, Shyr, Y, Liang, X, Ma, LJ, Donnert, EM, Roberts, JD, Zhang, X, Kon, V, Brown, NJ, Caprioli, RM, Fogo, AB. Proteomic patterns and prediction of glomerulosclerosis and its mechanisms. J Am Soc Nephrol, 16(10), 2967-75, 2005.

Gumieniak, O, Perlstein, TS, Hopkins, PN, Brown, NJ, Murphey, LJ, Jeunemaitre, X, Hollenberg, NK, Williams, GH. Thyroid function and blood pressure homeostasis in euthyroid subjects. J Clin Endocrinol Metab, 89(7), 3455-61, 2004.

Ma, LJ, Mao, SL, Taylor, KL, Kanjanabuch, T, Guan, Y, Zhang, Y, Brown, NJ, Swift, LL, McGuinness, OP, Wasserman, DH, Vaughan, DE, Fogo, AB. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes, 53(2), 336-46, 2004.

Muldowney, JA, Davis, SN, Vaughan, DE, Brown, NJ. NO synthase inhibition increases aldosterone in humans. Hypertension, 44(5), 739-45, 2004.

Murphey, LJ, Eccles, WK, Williams, GH, Brown, NJ. Loss of sodium modulation of plasma kinins in human hypertension. J Pharmacol Exp Ther, 308(3), 1046-52, 2004.

Nieman, MT, Warnock, M, Hasan, AA, Mahdi, F, Lucchesi, BR, Brown, NJ, Murphey, LJ, Schmaier, AH. The preparation and characterization of novel peptide antagonists to thrombin and factor VIIa and activation of protease-activated receptor 1. J Pharmacol Exp Ther, 311(2), 492-501, 2004.

Perlstein, TS, Gumieniak, O, Hopkins, PN, Murphey, LJ, Brown, NJ, Williams, GH, Hollenberg, NK, Fisher, ND. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney Int, 66(4), 1465-70, 2004.

Pretorius, M, McFarlane, JA, Vaughan, DE, Brown, NJ, Murphey, LJ. Angiotensin-converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass. Clin Pharmacol Ther, 76(4), 379-87, 2004.

Ridker, PM, Brown, NJ, Vaughan, DE, Harrison, DG, Mehta, JL. Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. Circulation, 109(25 Suppl 1), IV6-19, 2004.

Summar, ML, Gainer, JV, Pretorius, M, Malave, H, Harris, S, Hall, LD, Weisberg, A, Vaughan, DE, Christman, BW, Brown, NJ. Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function. Hypertension, 43(2), 186-91, 2004.

Bellamine, A, Wang, Y, Waterman, MR, Gainer, JV, Dawson, EP, Brown, NJ, Capdevila, JH. Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys, 409(1), 221-7, 2003.

Brown, NJ. Eplerenone: cardiovascular protection. Circulation, 107(19), 2512-8, 2003.

Eren, M, Painter, CA, Gleaves, LA, Schoenhard, JA, Atkinson, JB, Brown, NJ, Vaughan, DE. Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic mice. J Thromb Haemost, 1(11), 2389-96, 2003.

Murphey, LJ, Morrow, JD, Sawathiparnich, P, Williams, GH, Vaughan, DE, Brown, NJ. Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives. Free Radic Biol Med, 35(7), 711-8, 2003.

Pretorius, M, Murphey, LJ, McFarlane, JA, Vaughan, DE, Brown, NJ. Angiotensin-converting enzyme inhibition alters the fibrinolytic response to cardiopulmonary bypass. Circulation, 108(25), 3079-83, 2003.

Pretorius, M, Rosenbaum, D, Vaughan, DE, Brown, NJ. Angiotensin-converting enzyme inhibition increases human vascular tissue-type plasminogen activator release through endogenous bradykinin. Circulation, 107(4), 579-85, 2003.

Sawathiparnich, P, Murphey, LJ, Kumar, S, Vaughan, DE, Brown, NJ. Effect of combined AT1 receptor and aldosterone receptor antagonism on plasminogen activator inhibitor-1. J Clin Endocrinol Metab, 88(8), 3867-73, 2003.

Brown, NJ, Kumar, S, Painter, CA, Vaughan, DE. ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. Hypertension, 40(6), 859-65, 2002.

Brown, NJ, Vaughan, DE, Fogo, AB. Aldosterone and PAI-1: implications for renal injury. J Nephrol, 15(3), 230-5, 2002.

Brown, NJ, Vaughan, DE, Fogo, AB. The renin-angiotensin-aldosterone system and fibrinolysis in progressive renal disease. Semin Nephrol, 22(5), 399-406, 2002.

Chylack, LT, Brown, NP, Bron, A, Hurst, M, K??pcke, W, Thien, U, Schalch, W. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiol, 9(1), 49-80, 2002.

Kaikita, K, Schoenhard, JA, Painter, CA, Ripley, RT, Brown, NJ, Fogo, AB, Vaughan, DE. Potential roles of plasminogen activator system in coronary vascular remodeling induced by long-term nitric oxide synthase inhibition. J Mol Cell Cardiol, 34(6), 617-27, 2002.

Lefebvre, J, Murphey, LJ, Hartert, TV, Jiao Shan, R, Simmons, WH, Brown, NJ. Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema. Hypertension, 39(2 Pt 2), 460-4, 2002.

Meredith, S, Feldman, P, Frey, D, Giammarco, L, Hall, K, Arnold, K, Brown, NJ, Ray, WA. Improving medication use in newly admitted home healthcare patients: a randomized controlled trial. J Am Geriatr Soc, 50(9), 1484-91, 2002.

Moore, JH, Lamb, JM, Brown, NJ, Vaughan, DE. A comparison of combinatorial partitioning and linear regression for the detection of epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms on plasma PAI-1 levels. Clin Genet, 62(1), 74-9, 2002.

Moore, JH, Smolkin, ME, Lamb, JM, Brown, NJ, Vaughan, DE. The relationship between plasma t-PA and PAI-1 levels is dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms. Clin Genet, 62(1), 53-9, 2002.

Pretorius, M, Rosenbaum, DA, Lefebvre, J, Vaughan, DE, Brown, NJ. Smoking impairs bradykinin-stimulated t-PA release. Hypertension, 39(3), 767-71, 2002.

Rosenbaum, DA, Pretorius, M, Gainer, JV, Byrne, D, Murphey, LJ, Painter, CA, Vaughan, DE, Brown, NJ. Ethnicity affects vasodilation, but not endothelial tissue plasminogen activator release, in response to bradykinin. Arterioscler Thromb Vasc Biol, 22(6), 1023-8, 2002.

Sawathiparnich, P, Kumar, S, Vaughan, DE, Brown, NJ. Spironolactone abolishes the relationship between aldosterone and plasminogen activator inhibitor-1 in humans. J Clin Endocrinol Metab, 87(2), 448-52, 2002.

Srikumar, N, Brown, NJ, Hopkins, PN, Jeunemaitre, X, Hunt, SC, Vaughan, DE, Williams, GH. PAI-1 in human hypertension: relation to hypertensive groups. Am J Hypertens, 15(8), 683-90, 2002.

Brown, NJ, Murphey, LJ, Srikuma, N, Koschachuhanan, N, Williams, GH, Vaughan, DE. Interactive effect of PAI-1 4G/5G genotype and salt intake on PAI-1 antigen. Arterioscler Thromb Vasc Biol, 21(6), 1071-7, 2001.

Gainer, JV, Stein, CM, Neal, T, Vaughan, DE, Brown, NJ. Interactive Effect of Ethnicity and ACE Insertion/Deletion Polymorphism on Vascular Reactivity. Hypertension, 37(1), 46-51, 2001.

Kaikita, K, Fogo, AB, Ma, L, Schoenhard, JA, Brown, NJ, Vaughan, DE. Plasminogen activator inhibitor-1 deficiency prevents hypertension and vascular fibrosis in response to long-term nitric oxide synthase inhibition. Circulation, 104(7), 839-44, 2001.

Meredith, S, Feldman, PH, Frey, D, Hall, K, Arnold, K, Brown, NJ, Ray, WA. Possible medication errors in home healthcare patients. J Am Geriatr Soc, 49(6), 719-24, 2001.

Wilsdorf, T, Gainer, JV, Murphey, LJ, Vaughan, DE, Brown, NJ. Angiotensin-(1-7) does not affect vasodilator or TPA responses to bradykinin in human forearm. Hypertension, 37(4), 1136-40, 2001.

Murphey LJ, Gainer JV, Vaughan DE, Brown NJ. ACE I/D polymorphism modulates the human in vivo metabolism of bradykinin. Circulation 102:829-832, 2000.

Brown, NJ, Gainer, JV, Murphey, LJ, Vaughan, DE. Bradykinin stimulates tissue plasminogen activator release from human forearm vasculature through B(2) receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway. Circulation, 102(18), 2190-6, 2000.

Brown, NJ, Kim, KS, Chen, YQ, Blevins, LS, Nadeau, JH, Meranze, SG, Vaughan, DE. Synergistic effect of adrenal steroids and angiotensin II on plasminogen activator inhibitor-1 production. J Clin Endocrinol Metab, 85(1), 336-44, 2000.

Brown, NJ, Nakamura, S, Ma, L, Nakamura, I, Donnert, E, Freeman, M, Vaughan, DE, Fogo, AB. Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney Int, 58(3), 1219-27, 2000.

Brown, NJ, Vaughan, DE. Prothrombotic effects of angiotensin. Adv Intern Med, 45, 419-29, 2000.

Gainer, JV, Brown, NJ, Bachvarova, M, Bastien, L, Maltais, I, Marceau, F, Bachvarov, DR. Altered frequency of a promoter polymorphism of the kinin B2 receptor gene in hypertensive African-Americans. Am J Hypertens, 13(12), 1268-73, 2000.

Kim, KS, Kumar, S, Simmons, WH, Brown, NJ. Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans. J Pharmacol Exp Ther, 292(1), 295-8, 2000.

Murphey, LJ, Gainer, JV, Vaughan, DE, Brown, NJ. Angiotensin-converting enzyme insertion/deletion polymorphism modulates the human in vivo metabolism of bradykinin. Circulation, 102(8), 829-32, 2000.

Murphey, LJ, Hachey, DL, Oates, JA, Morrow, JD, Brown, NJ. Metabolism of bradykinin In vivo in humans: identification of BK1-5 as a stable plasma peptide metabolite. J Pharmacol Exp Ther, 294(1), 263-9, 2000.

Murphey, LJ, Kumar, S, Brown, NJ. Endogenous bradykinin and the renin and pressor responses to furosemide in humans. J Pharmacol Exp Ther, 295(2), 644-8, 2000.

Xie, HG, Stein, CM, Kim, RB, Gainer, JV, Sofowora, G, Dishy, V, Brown, NJ, Goree, RE, Haines, JL, Wood, AJ. Human beta2-adrenergic receptor polymorphisms: no association with essential hypertension in black or white Americans. Clin Pharmacol Ther, 67(6), 670-5, 2000.

Brown, NJ, Agirbasli, M, Vaughan, DE. Comparative effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on plasma fibrinolytic balance in humans. Hypertension, 34(2), 285-90, 1999.

Brown, NJ, Gainer, JV, Stein, CM, Vaughan, DE. Bradykinin stimulates tissue plasminogen activator release in human vasculature. Hypertension, 33(6), 1431-5, 1999.

Xie, HG, Kim, RB, Stein, CM, Gainer, JV, Brown, NJ, Wood, AJ. Alpha1A-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension. Pharmacogenetics, 9(5), 651-6, 1999.

Xie, HG, Stein, CM, Kim, RB, Xiao, ZS, He, N, Zhou, HH, Gainer, JV, Brown, NJ, Haines, JL, Wood, AJ. Frequency of functionally important beta-2 adrenoceptor polymorphisms varies markedly among African-American, Caucasian and Chinese individuals. Pharmacogenetics, 9(4), 511-6, 1999.

Brown, NJ, Agirbasli, MA, Williams, GH, Litchfield, WR, Vaughan, DE. Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. Hypertension, 32(6), 965-71, 1998.

Brown, NJ, Blais, C, Gandhi, SK, Adam, A. ACE insertion/deletion genotype affects bradykinin metabolism. J Cardiovasc Pharmacol, 32(3), 373-7, 1998.

Brown, NJ, Griffin, MR, Ray, WA, Meredith, S, Beers, MH, Marren, J, Robles, M, Stergachis, A, Wood, AJ, Avorn, J. A model for improving medication use in home health care patients. J Am Pharm Assoc (Wash), 38(6), 696-702, 1998.

Brown, NJ, Vaughan, DE. Angiotensin-converting enzyme inhibitors. Circulation, 97(14), 1411-20, 1998.

Gainer, JV, Morrow, JD, Loveland, A, King, DJ, Brown, NJ. Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med, 339(18), 1285-92, 1998.

Gandhi, SK, Gainer, J, King, D, Brown, NJ. Gender affects renal vasoconstrictor response to Ang I and Ang II. Hypertension, 31(1), 90-6, 1998.

Brown, NJ, Nadeau, JH, Vaughan, DE. Selective stimulation of tissue-type plasminogen activator (t-PA) in vivo by infusion of bradykinin. Thromb Haemost, 77(3), 522-5, 1997.

Brown, NJ, Snowden, M, Griffin, MR. Recurrent angiotensin-converting enzyme inhibitor--associated angioedema. JAMA, 278(3), 232-3, 1997.

Gainer, JV, Hunley, TE, Kon, V, Nadeau, JH, Muldowney, JA, Brown, NJ. Angiotensin II type I receptor polymorphism in African Americans lower frequency of the C1166 variant. Biochem Mol Biol Int, 43(1), 227-31, 1997.

Brown, NJ, Ray, WA, Snowden, M, Griffin, MR. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther, 60(1), 8-13, 1996.

Brown, NJ, Ryder, D, Gainer, JV, Morrow, JD, Nadeau, J. Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin. J Pharmacol Exp Ther, 279(2), 703-12, 1996.

Gainer, JV, Nadeau, JH, Ryder, D, Brown, NJ. Increased sensitivity to bradykinin among African Americans. J Allergy Clin Immunol, 98(2), 283-7, 1996.

Gandhi, SK, Ryder, DH, Brown, NJ. Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans. Hypertension, 28(6), 961-6, 1996.

Hunley, TE, Julian, BA, Phillips, JA, Summar, ML, Yoshida, H, Horn, RG, Brown, NJ, Fogo, A, Ichikawa, I, Kon, V. Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. Kidney Int, 49(2), 571-7, 1996.

Daniel, VC, Minton, TA, Brown, NJ, Nadeau, JH, Morrow, JD. Simplified assay for the quantification of 2,3-dinor-6-keto-prostaglandin F1 alpha by gas chromatography-mass spectrometry. J Chromatogr B Biomed Appl, 653(2), 117-22, 1994.

Brown NJ, Nadeau JH. Does race predispose to ACEI-associated angioedema? Ann Intern Med, 119:1224, 1993.

Brown, NJ, Ryder, D, Nadeau, J. Caffeine attenuates the renal vascular response to angiotensin II infusion. Hypertension, 22(6), 847-52, 1993.

Brown, NJ, McKenzie, S, Decker, MD. Case report: fatal pulmonary toxoplasmosis following chemotherapy. Am J Med Sci, 302(3), 152-4, 1991.

Brown, NJ, Porter, J, Ryder, D, Branch, RA. Caffeine potentiates the renin response to diazoxide in man. Evidence for a regulatory role of endogenous adenosine. J Pharmacol Exp Ther, 256(1), 56-61, 1991.

Brown, NJ, Ryder, D, Branch, RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther, 50(4), 363-71, 1991.

Brown, NJ. Octreotide: a long-acting somatostatin analog. Am J Med Sci, 300(4), 267-73, 1990.

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