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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 

VICC toll-free number 1-877-936-8422

Nancy J.  Brown

Nancy J. Brown, M.D.

Chair, Department of Medicine
Hugh J. Morgan Professor of Medicine
Professor of Pharmacology
Physician-in-Chief
Researcher

Contact Information:

Vanderbilt University Medical Center
D3100 Medical Center North
Nashville, TN 37232-6602
615-343-8701
Fax: 615-343-2551

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.

Publications
  • Gamboa JL, Billings FT, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, Roberts LJ, Himmelfarb J, Ikizler TA, Brown NJ. Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiol Rep. 2016 May; 4(9): PMID: 27162261, PII: 4/9/e12780, DOI: 10.14814/phy2.12780, ISSN: 2051-817X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27162261.
  • Gamboa JL, Devin JK, Ramirez CE, Yu C, Nian H, Lee RH, Brown NJ. Comparative effects of immediate-release and extended-release aspirin on basal and bradykinin-stimulated excretion of thromboxane and prostacyclin metabolites. Pharmacol Res Perspect. 2016 Apr; 4(2): e00221. PMID: 27069632, PMCID: PMC4804312, PII: PRP2221, DOI: 10.1002/prp2.221, ISSN: 2052-1707.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27069632.
  • Sharma A, Bhatt DL, Calvo G, Brown NJ, Zannad F, Mentz RJ. Heart failure event definitions in drug trials in patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2016 Apr; 4(4): 294-6. PMID: 27016320, PII: S2213-8587(16)00049-8, DOI: 10.1016/S2213-8587(16)00049-8, ISSN: 2213-8595.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27016320.
  • Semler MW, Marney AM, Rice TW, Nian H, Yu C, Wheeler AP, Brown NJ, . B-type Natriuretic Peptide, Aldosterone, and Fluid Management in Acute Respiratory Distress Syndrome. Chest [print-electronic]. 2016 Mar 3/23/2016; PMID: 27018313, PII: S0012-3692(16)45714-4, DOI: 10.1016/j.chest.2016.03.017, ISSN: 1931-3543.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27018313.
  • Hubers SA, Brown NJ. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition. Circulation. 2016 Mar 3/15/2016; 133(11): 1115-24. PMID: 26976916, PII: CIRCULATIONAHA.115.018622, DOI: 10.1161/CIRCULATIONAHA.115.018622, ISSN: 1524-4539.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26976916.
  • Billings FT, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ. High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial. JAMA. 2016 Mar 3/1/2016; 315(9): 877-88. PMID: 26906014, PII: 2492851, DOI: 10.1001/jama.2016.0548, ISSN: 1538-3598.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26906014.
  • Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. J. Clin. Endocrinol. Metab [print-electronic]. 2015 Dec; 100(12): 4533-40. PMID: 26580240, PMCID: PMC4667163, DOI: 10.1210/jc.2015-3415, ISSN: 1945-7197.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26580240.
  • Wu JH, Marchioli R, Silletta MG, Masson S, Sellke FW, Libby P, Milne GL, Brown NJ, Lombardi F, Damiano RJ, Marsala J, Rinaldi M, Domenech A, Simon C, Tavazzi L, Mozaffarian D. Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Trial. J Am Heart Assoc. 2015 May; 4(5): PMID: 25994442, PMCID: PMC4599415, PII: JAHA.115.001886, DOI: 10.1161/JAHA.115.001886, ISSN: 2047-9980.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25994442.
  • Bowton EA, Collier SP, Wang X, Sutcliffe CB, Van Driest SL, Couch LJ, Herrera M, Jerome RN, Slebos RJ, Alborn WE, Liebler DC, McNaughton CD, Mernaugh RL, Wells QS, Brown NJ, Roden DM, Pulley JM. Phenotype-Driven Plasma Biobanking Strategies and Methods. J Pers Med. 2015; 5(2): 140-52. PMID: 26110578, PMCID: PMC4493492, PII: jpm5020140, DOI: 10.3390/jpm5020140, ISSN: 2075-4426.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26110578.
  • Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA. Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis--a randomized cross-over study. BMC Nephrol. 2015; 16: 167. PMID: 26494370, PMCID: PMC4618919, PII: 10.1186/s12882-015-0162-x, DOI: 10.1186/s12882-015-0162-x, ISSN: 1471-2369.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26494370.
  • White MJ, Kodaman NM, Harder RH, Asselbergs FW, Vaughan DE, Brown NJ, Moore JH, Williams SM. Genetics of Plasminogen Activator Inhibitor-1 (PAI-1) in a Ghanaian Population. PLoS ONE. 2015; 10(8): e0136379. PMID: 26322636, PMCID: PMC4556460, PII: PONE-D-15-02805, DOI: 10.1371/journal.pone.0136379, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26322636.
  • Sidorova TN, Mace LC, Wells KS, Yermalitskaya LV, Su PF, Shyr Y, Atkinson JB, Fogo AB, Prinsen JK, Byrne JG, Petracek MR, Greelish JP, Hoff SJ, Ball SK, Glabe CG, Brown NJ, Barnett JV, Murray KT. Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?. J Am Heart Assoc. 2014 Dec; 3(6): e001384. PMID: 25468655, PMCID: PMC4338732, PII: jah3772, DOI: 10.1161/JAHA.114.001384, ISSN: 2047-9980.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25468655.
  • Luther JM, Byrne LM, Yu C, Wang TJ, Brown NJ. Dietary sodium restriction decreases insulin secretion without affecting insulin sensitivity in humans. J. Clin. Endocrinol. Metab [print-electronic]. 2014 Oct; 99(10): E1895-902. PMID: 25029426, PMCID: PMC4184066, DOI: 10.1210/jc.2014-2122, ISSN: 1945-7197.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25029426.
  • Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins Other Lipid Mediat [print-electronic]. 2014 Oct; 113-115: 38-44. PMID: 25173047, PMCID: PMC4253976, PII: S1098-8823(14)00032-X, DOI: 10.1016/j.prostaglandins.2014.08.001, ISSN: 1098-8823.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25173047.
  • Devin JK, Pretorius M, Nian H, Yu C, Billings FT, Brown NJ. Dipeptidyl-peptidase 4 inhibition and the vascular effects of glucagon-like peptide-1 and brain natriuretic peptide in the human forearm. J Am Heart Assoc. 2014 Aug; 3(4): PMID: 25158865, PMCID: PMC4310400, PII: jah3617, DOI: 10.1161/JAHA.114.001075, ISSN: 2047-9980.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25158865.
  • Laffer CL, Elijovich F, Eckert GJ, Tu W, Pratt JH, Brown NJ. Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans. J Am Soc Hypertens [print-electronic]. 2014 Jul; 8(7): 475-80. PMID: 25064769, PMCID: PMC4115247, PII: S1933-1711(14)00546-4, DOI: 10.1016/j.jash.2014.04.011, ISSN: 1878-7436.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25064769.
  • Devin JK, Pretorius M, Nian H, Yu C, Billings FT, Brown NJ. Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. Hypertension [print-electronic]. 2014 May; 63(5): 951-7. PMID: 24516103, PMCID: PMC3984385, PII: HYPERTENSIONAHA.113.02767, DOI: 10.1161/HYPERTENSIONAHA.113.02767, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24516103.
  • Sidorova TN, Mace LC, Wells KS, Yermalitskaya LV, Su PF, Shyr Y, Byrne JG, Petracek MR, Greelish JP, Hoff SJ, Ball SK, Glabe CG, Brown NJ, Barnett JV, Murray KT. Quantitative Imaging of Preamyloid Oligomers, a Novel Structural Abnormality, in Human Atrial Samples. J. Histochem. Cytochem [print-electronic]. 2014 Apr 4/30/2014; 62(7): 479-87. PMID: 24789805, PMCID: PMC4072180, PII: 0022155414535782, DOI: 10.1369/0022155414535782, ISSN: 1551-5044.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24789805.
  • 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 [print-electronic]. 2013 Oct 10/15/2013; 937: 44-53. PMID: 24013190, PMCID: PMC3800555, PII: S1570-0232(13)00431-5, DOI: 10.1016/j.jchromb.2013.08.010, ISSN: 1873-376X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24013190.
  • Straka B, Nian H, Sloan C, Byrd JB, Woodard-Grice A, Yu C, Stone E, Steven G, Hartert T, Teo KK, Pare G, McCarty CA, Brown NJ. Pollen count and presentation of angiotensin-converting enzyme inhibitor-associated angioedema. J Allergy Clin Immunol Pract [print-electronic]. 2013 Sep; 1(5): 468-73.e1. PMID: 24565618, PMCID: PMC4042396, PII: S2213-2198(13)00225-0, DOI: 10.1016/j.jaip.2013.05.003, ISSN: 2213-2201.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24565618.
  • Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol [print-electronic]. 2013 Aug; 9(8): 459-69. PMID: 23774812, PMCID: PMC3922409, PII: nrneph.2013.110, DOI: 10.1038/nrneph.2013.110, ISSN: 1759-507X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23774812.
  • 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 [print-electronic]. 2013 Apr; 93(4): 326-34. PMID: 23361105, PMCID: PMC4031681, PII: clpt2012249, DOI: 10.1038/clpt.2012.249, ISSN: 1532-6535.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23361105.
  • Gilbert K, Nian H, Yu C, Luther JM, Brown NJ. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension. J. Hypertens. 2013 Apr; 31(4): 820-9. PMID: 23385647, PMCID: PMC3800119, DOI: 10.1097/HJH.0b013e32835e8227, ISSN: 1473-5598.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23385647.
  • 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. 2013 Apr; 88(4): 512-8. PMID: 23425987, PMCID: PMC3638874, DOI: 10.1097/ACM.0b013e318285800f, ISSN: 1938-808X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23425987.
  • Brown NJ. Developing physician-scientists: a perspective. Trans. Am. Clin. Climatol. Assoc. 2013; 124: 218-29. PMID: 23874028, PMCID: PMC3715951, ISSN: 0065-7778.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23874028.
  • 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. 2012 Oct; 40(10): 2805-12. PMID: 22824930, PMCID: PMC3588582, DOI: 10.1097/CCM.0b013e31825b8be2, ISSN: 1530-0293.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22824930.
  • 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 [print-electronic]. 2012 Sep; 82(6): 643-51. PMID: 22622494, PMCID: PMC3434275, PII: ki2012170, DOI: 10.1038/ki.2012.170, ISSN: 1523-1755.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22622494.
  • 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 [print-electronic]. 2012 Jul; 23(7): 1221-8. PMID: 22626819, PMCID: PMC3380645, PII: ASN.2011090940, DOI: 10.1681/ASN.2011090940, ISSN: 1533-3450.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22626819.
  • 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. 2012 Jun; 91(6): 1065-73. PMID: 22549281, PMCID: PMC3822756, PII: clpt2011356, DOI: 10.1038/clpt.2011.356, ISSN: 1532-6535.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22549281.
  • Brown NJ. Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies. J Am Soc Hypertens [print-electronic]. 2012 May; 6(3): 163-8. PMID: 22433315, PMCID: PMC3422131, PII: S1933-1711(12)00062-9, DOI: 10.1016/j.jash.2012.02.003, ISSN: 1878-7436.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22433315.
  • 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 [print-electronic]. 2012 Apr; 59(4): 893-8. PMID: 22353614, PMCID: PMC3402551, PII: HYPERTENSIONAHA.111.189589, DOI: 10.1161/HYPERTENSIONAHA.111.189589, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22353614.
  • Brown NJ. Patient-oriented research in the era of personalized medicine. Clin Transl Sci [print-electronic]. 2012 Apr; 5(2): 119-20. PMID: 22507115, DOI: 10.1111/j.1752-8062.2011.00394.x, ISSN: 1752-8062.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22507115.
  • 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 [print-electronic]. 2012 Feb; 23(2): 334-42. PMID: 22158433, PMCID: PMC3269170, PII: ASN.2011030287, DOI: 10.1681/ASN.2011030287, ISSN: 1533-3450.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22158433.
  • 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 [print-electronic]. 2012; 7(2): e32338. PMID: 22384221, PMCID: PMC3285683, PII: PONE-D-11-18969, DOI: 10.1371/journal.pone.0032338, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22384221.
  • Luther JM, Brown NJ. The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol. Sci [print-electronic]. 2011 Dec; 32(12): 734-9. PMID: 21880378, PMCID: PMC3223326, PII: S0165-6147(11)00138-6, DOI: 10.1016/j.tips.2011.07.006, ISSN: 1873-3735.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21880378.
  • 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. 2011 Aug; 86(8): 968-73. PMID: 21694562, DOI: 10.1097/ACM.0b013e318222317e, ISSN: 1938-808X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21694562.
  • 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 [print-electronic]. 2011 Aug; 54(8): 2152-63. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9, ISSN: 1432-0428.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21519965.
  • Garg R, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metab. Clin. Exp [print-electronic]. 2011 Jul; 60(7): 965-8. PMID: 21036373, PMCID: PMC3036792, PII: S0026-0495(10)00329-X, DOI: 10.1016/j.metabol.2010.09.005, ISSN: 1532-8600.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21036373.
  • 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 [print-electronic]. 2011 Jan; 57(1): 116-22. PMID: 21098312, PMCID: PMC3020911, PII: HYPERTENSIONAHA.110.161695, DOI: 10.1161/HYPERTENSIONAHA.110.161695, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21098312.
  • Brown NJ. This is not Dr. Conn's aldosterone anymore. Trans. Am. Clin. Climatol. Assoc. 2011; 122: 229-43. PMID: 21686229, PMCID: PMC3116341, ISSN: 0065-7778.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21686229.
  • 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. 2010 Dec; 24(6): 913-20. PMID: 20599398, PMCID: PMC2992577, PII: S1053-0770(10)00121-7, DOI: 10.1053/j.jvca.2010.03.024, ISSN: 1532-8422.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20599398.
  • 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. 2010 Nov; 65(11): 1381-7. PMID: 20557296, PMCID: PMC3305268, PII: ALL2398, DOI: 10.1111/j.1398-9995.2010.02398.x, ISSN: 1398-9995.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20557296.
  • Brown NJ. Therapeutic potential of plasminogen activator inhibitor-1 inhibitors. Ther Adv Cardiovasc Dis [print-electronic]. 2010 Oct; 4(5): 315-24. PMID: 20660535, PII: 1753944710379126, DOI: 10.1177/1753944710379126, ISSN: 1753-9455.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20660535.
  • 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 [print-electronic]. 2010 Sep; 95(9): E75-9. PMID: 20631015, PMCID: PMC2936061, PII: jc.2010-0270, DOI: 10.1210/jc.2010-0270, ISSN: 1945-7197.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20631015.
  • 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. 2010 Sep; 20(9): 532-6. PMID: 20625347, PMCID: PMC2945219, DOI: 10.1097/FPC.0b013e32833d3acb, ISSN: 1744-6880.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20625347.
  • 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 [print-electronic]. 2010 Jul 7/15/2010; 49(2): 301-5. PMID: 20423727, PMCID: PMC2916026, PII: S0891-5849(10)00254-6, DOI: 10.1016/j.freeradbiomed.2010.04.023, ISSN: 1873-4596.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20423727.
  • Gilbert KC, Brown NJ. Aldosterone and inflammation. Curr Opin Endocrinol Diabetes Obes. 2010 Jun; 17(3): 199-204. PMID: 20422780, PMCID: PMC4079531, ISSN: 1752-2978.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20422780.
  • 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 [print-electronic]. 2010 May; 55(5): 1239-45. PMID: 20308605, PMCID: PMC2880505, PII: HYPERTENSIONAHA.109.147595, DOI: 10.1161/HYPERTENSIONAHA.109.147595, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20308605.
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  • 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. 2003 Aug; 88(8): 3867-73. PMID: 12915681, DOI: 10.1210/jc.2003-030374, ISSN: 0021-972X.
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  • Brown NJ. Eplerenone: cardiovascular protection. Circulation. 2003 May 5/20/2003; 107(19): 2512-8. PMID: 12756192, PII: 107/19/2512, DOI: 10.1161/01.CIR.0000071081.35693.9A, ISSN: 1524-4539.
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  • Pretorius M, Rosenbaum D, Vaughan DE, Brown NJ. Angiotensin-converting enzyme inhibition increases human vascular tissue-type plasminogen activator release through endogenous bradykinin. Circulation. 2003 Feb 2/4/2003; 107(4): 579-85. PMID: 12566370, ISSN: 1524-4539.
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  • 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. 2003 Jan 1/1/2003; 409(1): 221-7. PMID: 12464262, PII: S0003986102005453, ISSN: 0003-9861.
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  • Brown NJ, Kumar S, Painter CA, Vaughan DE. ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. Hypertension. 2002 Dec; 40(6): 859-65. PMID: 12468570, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12468570.
  • Brown NJ, Vaughan DE, Fogo AB. The renin-angiotensin-aldosterone system and fibrinolysis in progressive renal disease. Semin. Nephrol. 2002 Sep; 22(5): 399-406. PMID: 12224047, PII: S027092950250053X, ISSN: 0270-9295.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12224047.
  • 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. 2002 Sep; 50(9): 1484-91. PMID: 12383144, PII: jgs50402, ISSN: 0002-8614.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12383144.
  • 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. 2002 Aug; 15(8): 683-90. PMID: 12160190, PII: S0895706102029527, ISSN: 0895-7061.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12160190.
  • 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. 2002 Jul; 62(1): 74-9. PMID: 12123491, PII: cge620110, ISSN: 0009-9163.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12123491.
  • 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. 2002 Jul; 62(1): 53-9. PMID: 12123488, PII: cge620107, ISSN: 0009-9163.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12123488.
  • 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. 2002 Jun 6/1/2002; 22(6): 1023-8. PMID: 12067915, ISSN: 1524-4636.
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  • 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. 2002 Jun; 34(6): 617-27. PMID: 12054849, PII: S0022282802920018, DOI: 10.1006/jmcc.2002.2001, ISSN: 0022-2828.
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  • Brown NJ, Vaughan DE, Fogo AB. Aldosterone and PAI-1: implications for renal injury. J. Nephrol. 2002 May; 15(3): 230-5. PMID: 12113592, ISSN: 1121-8428.
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  • Pretorius M, Rosenbaum DA, Lefebvre J, Vaughan DE, Brown NJ. Smoking impairs bradykinin-stimulated t-PA release. Hypertension. 2002 Mar 3/1/2002; 39(3): 767-71. PMID: 11897760, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11897760.
  • 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. 2002 Feb; 39(2 Pt 2): 460-4. PMID: 11882590, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11882590.
  • 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. 2002 Feb; 87(2): 448-52. PMID: 11836266, DOI: 10.1210/jcem.87.2.7980, ISSN: 0021-972X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11836266.
  • 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. 2001 Aug 8/14/2001; 104(7): 839-44. PMID: 11502712, ISSN: 1524-4539.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11502712.
  • 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. 2001 Jun; 21(6): 1071-7. PMID: 11397722, ISSN: 1524-4636.
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  • 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. 2001 Jun; 49(6): 719-24. PMID: 11454109, PII: jgs49147, ISSN: 0002-8614.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11454109.
  • 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. 2001 Apr; 37(4): 1136-40. PMID: 11304515, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11304515.
  • Gainer JV, Stein CM, Neal T, Vaughan DE, Brown NJ. Interactive Effect of Ethnicity and ACE Insertion/Deletion Polymorphism on Vascular Reactivity. Hypertension. 2001 Jan; 37(1): 46-51. PMID: 11208755, ISSN: 1524-4563.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11208755.
  • 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. 2000 Dec; 13(12): 1268-73. PMID: 11130770, PII: S0895706100012152, ISSN: 0895-7061.
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  • Murphey LJ, Kumar S, Brown NJ. Endogenous bradykinin and the renin and pressor responses to furosemide in humans. J. Pharmacol. Exp. Ther. 2000 Nov; 295(2): 644-8. PMID: 11046100, ISSN: 0022-3565.
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  • 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. 2000 Oct 10/31/2000; 102(18): 2190-6. PMID: 11056091, ISSN: 1524-4539.
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  • 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. 2000 Sep; 58(3): 1219-27. PMID: 10972684, PII: kid277, DOI: 10.1046/j.1523-1755.2000.00277.x, ISSN: 0085-2538.
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  • Murphey LJ, Gainer JV, Vaughan DE, Brown NJ. Angiotensin-converting enzyme insertion/deletion polymorphism modulates the human in vivo metabolism of bradykinin. Circulation. 2000 Aug 8/22/2000; 102(8): 829-32. PMID: 10952948, ISSN: 1524-4539.
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  • 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. 2000 Jul; 294(1): 263-9. PMID: 10871321, ISSN: 0022-3565.
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  • 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. 2000 Jun; 67(6): 670-5. PMID: 10872649, PII: S0009-9236(00)45798-X, DOI: 10.1067/mcp.2000.106293, ISSN: 0009-9236.
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  • 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. 2000 Jan; 85(1): 336-44. PMID: 10634408, DOI: 10.1210/jcem.85.1.6305, ISSN: 0021-972X.
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  • 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. 2000 Jan; 292(1): 295-8. PMID: 10604961, ISSN: 0022-3565.
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  • Brown NJ, Vaughan DE. Prothrombotic effects of angiotensin. Adv Intern Med. 2000; 45: 419-29. PMID: 10635057, ISSN: 0065-2822.
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  • Xie HG, Kim RB, Stein CM, Gainer JV, Brown NJ, Wood AJ. Alpha1A-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension. Pharmacogenetics. 1999 Oct; 9(5): 651-6. PMID: 10591546, ISSN: 0960-314X.
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  • 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. 1999 Aug; 34(2): 285-90. PMID: 10454455, ISSN: 0194-911X.
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  • 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. 1999 Aug; 9(4): 511-6. PMID: 10780271, ISSN: 0960-314X.
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  • 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. 1998 Dec; 32(6): 965-71. PMID: 9856958, ISSN: 0194-911X.
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  • 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. 1998 Oct 10/29/1998; 339(18): 1285-92. PMID: 9791144, DOI: 10.1056/NEJM199810293391804, ISSN: 0028-4793.
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  • Brown NJ, Blais C, Gandhi SK, Adam A. ACE insertion/deletion genotype affects bradykinin metabolism. J. Cardiovasc. Pharmacol. 1998 Sep; 32(3): 373-7. PMID: 9733349, ISSN: 0160-2446.
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  • 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. 1997 Sep; 43(1): 227-31. PMID: 9315301, ISSN: 1039-9712.
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  • Gandhi SK, Ryder DH, Brown NJ. Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans. Hypertension. 1996 Dec; 28(6): 961-6. PMID: 8952583, ISSN: 0194-911X.
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