Genes and Fibrinolytic Capacity of Human Endothelium - Full Text View

Purpose

To conduct several studies on genes and the fibrinolytic capacity of human endothelium.

Condition	Intervention
Cardiovascular Diseases Heart Diseases Thrombosis Blood Disease Coronary Disease	Drug: angiotensin converting enzyme inhibitor

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Genes and Fibrinolytic Capacity of Human Endothelium

Resource links provided by NLM:

MedlinePlus related topics: Blood Disorders Coronary Artery Disease Heart Diseases

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Net t-LA release [ Time Frame: minutes ] [ Designated as safety issue: No ]
Net t-PA release from the forearm vasculature

Enrollment:	48
Study Start Date:	August 2000
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Effect of smoking on t-PA release	Drug: angiotensin converting enzyme inhibitor

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

No eligibility criteria

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00139503

Sponsors and Collaborators

Vanderbilt University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Nancy Brown

Vanderbilt University

More Information

Publications:

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. 2005 Nov;78(5):477-85.

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. 2005 Nov;25(11):2435-40. Epub 2005 Sep 15.

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. 2005 Aug;46(2):313-20. Epub 2005 Jul 5.

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. 2005 Jan 4;111(1):63-9. Epub 2004 Dec 20.

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. 2004 Oct;76(4):379-87.

Muldowney JA 3rd, Davis SN, Vaughan DE, Brown NJ. NO synthase inhibition increases aldosterone in humans. Hypertension. 2004 Nov;44(5):739-45. Epub 2004 Sep 20.

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. 2004 Nov;311(2):492-501. Epub 2004 Jun 21.

Murphey LJ, Eccles WK, Williams GH, Brown NJ. Loss of sodium modulation of plasma kinins in human hypertension. J Pharmacol Exp Ther. 2004 Mar;308(3):1046-52. Epub 2004 Jan 8.

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. 2004 Feb;43(2):186-91. Epub 2004 Jan 12.

Pretorius M, Murphey LJ, McFarlane JA, Vaughan DE, Brown NJ. Angiotensin-converting enzyme inhibition alters the fibrinolytic response to cardiopulmonary bypass. Circulation. 2003 Dec 23;108(25):3079-83. Epub 2003 Dec 1.

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. 2003 Oct 1;35(7):711-8.

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.

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 4;107(4):579-85.

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.

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. Review.

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.

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.

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

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 1;22(6):1023-8.

Pretorius M, Rosenbaum DA, Lefebvre J, Vaughan DE, Brown NJ. Smoking impairs bradykinin-stimulated t-PA release. Hypertension. 2002 Mar 1;39(3):767-71.

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.

Brown NJ, Abbas A, Byrne D, Schoenhard JA, Vaughan DE. Comparative effects of estrogen and angiotensin-converting enzyme inhibition on plasminogen activator inhibitor-1 in healthy postmenopausal women. Circulation. 2002 Jan 22;105(3):304-9.

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.

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 31;102(18):2190-6.

Responsible Party:	Nancy J. Brown, Professor and Chair, Department of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00139503 History of Changes
Other Study ID Numbers:	245, R01HL065193
Study First Received:	August 29, 2005
Last Updated:	December 18, 2012
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Cardiovascular Diseases
Coronary Disease
Coronary Artery Disease
Heart Diseases
Hematologic Diseases
Thrombosis
Myocardial Ischemia
Vascular Diseases

Arteriosclerosis
Arterial Occlusive Diseases
Embolism and Thrombosis
Angiotensin-Converting Enzyme Inhibitors
Enzyme Inhibitors
Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013