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We experienced challenges recruiting unmedicated women with high blood pressure for the intervention.
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
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The purpose of this study is to investigate the role of ET-1 in mediating vasoconstrictor tone in hypertensive postmenopausal women (PMW) alone and in combination with a commonly prescribed Angiotensin II (ANG II) antagonist. The long term goal is to understand the mechanisms contributing to hypertension (HTN) in PMW. This study is the first step in reaching our goal.
Cardiovascular disease (CVD) is the leading cause of death in women, and mortality from CVD is higher in PMW compared to age-matched men. PMW are at a greater risk for developing HTN, a major risk factor for CVD. They are also more likely to have uncontrolled or resistant HTN despite medication.
ANG II is a common therapeutic target for the treatment HTN. ANG II blockade is highly effective in normalizing blood pressure (BP) in hypertensive male rats, but does not reduce BP to the same degree in hypertensive post menopausal female rats. Endothelin-1 (ET-1) receptor antagonists reduce BP in hypertensive postmenopausal female rats, but have no effect on males. Thus the mechanisms contributing to HTN in female rats and likely women, particularly after menopause, are complex, multifactorial and not completely understood.
After menopause, the vasoconstrictor effects of both ANG II and ET-1 are amplified in animal models. As such, these two predominant pathways may contribute to the high incidence of HTN in PMW. ET-1 is a potent vasoconstrictor produced and released by endothelial cells that binds to two receptor subtypes, ET-A and ET-B. While both receptors are located on vascular smooth muscle (VSM) and mediate vasoconstriction, ET-B receptors are also located on the endothelium and mediate vasodilation via nitric oxide.
Importantly, the production of ET-1 and expression of ET-A and B receptors can be modulated by hormones such as estradiol and ANG II. Estradiol attenuates ET-1 production, and reduces ET-1 mediated vasoconstriction via an ET-B receptor mechanism in vitro. Thus, decline in estradiol after menopause may enhance vasoconstrictor tone via ET-1 and lead to HTN. ET-1 also potentiates the vasoconstrictor effects of ANG II since the vasoconstrictor and hypertensive effects of ANG II are ameliorated by ET-1 receptor blockade. Additionally, ANG II stimulates the synthesis of ET-1 and upregulates ET-A and ET-B receptor expression on VSM. The ANG II receptor antagonist Losartan reduces ET-A and ET-B receptor expression and attenuates the constrictor effects of ET-1 in a diabetic rat model. Therefore, ET-1 is an important independent factor contributing to HTN in PMW, but therapeutic agents targeting both ANG II and ET-1 may have greater efficacy given their interactions.
The investigators propose a comprehensive assessment of vascular function by measuring blood flow responses in the cutaneous circulation during perfusion of ET-1 receptor antagonists via microdialysis, combined with measures of intracellular protein and receptor expression of endothelial cells and skin punch biopsies collected from normotensive and hypertensive PMW. Investigators central hypothesis is that hypertensive PMW have greater ET-1 mediated vasoconstrictor tone due to increased ET-1 expression, down-regulation of ET-B receptors on endothelial cells and up-regulation of both ET-A and ET-B receptors on VSM leading to increased vasoconstriction and HTN. Investigators further hypothesize that ANG II exacerbates the increase in ET-1, and ET-A and ET-B receptor expression contributing to exaggerated constriction with HTN in PMW.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normotensive | Other | Normotensive PMW will complete an experimental visit to assess vascular function. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visit to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
|
| Hypertensives | Experimental | Hypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Normotensive | Other | FMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors. |
| Measure | Description | Time Frame |
|---|---|---|
| ET-1 Mediated Constriction | Cutaneous blood flow is measured via laser Doppler flowmetry during cutaneous microdialysis perfusions of ET-A and ET-B receptor antagonists as previously described by Wenner MM in 2017(see reference list). | Each participant was assessed at baseline and 2 weeks later. |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelin Receptor A and B Expression | ET-A and ET-B receptors will be examined using immunocytochemistry from 3mm skin punch biopsy in women pre/post losartan administration. This Secondary aim was not complete due to difficulty with enrollment (no data collected in these groups). | Baseline and 2 weeks later |
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Inclusion Criteria: - Women.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Megan Wenner, Ph.D | University of Delaware | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Delaware | Newark | Delaware | 19716 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23283859 | Background | Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013 Jan 1;127(1):143-52. doi: 10.1161/CIR.0b013e318282ab8f. No abstract available. | |
| 19470884 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Normotensive | Normotensive postmenopausal women (PMW) will complete an experimental visit to assess vascular function. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visit to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. Endothelin-1 (ET-1) mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. Normotensive: FMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors. |
| FG001 | Hypertensives | Hypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Normotensive BP <130/80mmHg Hypertensive BP >130/80mmHg
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| ID | Title | Description |
|---|---|---|
| BG000 | Normotensive | Normotensive PMW will complete an experimental visit to assess vascular function. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visit to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. Normotensive: FMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | ET-1 Mediated Constriction | Cutaneous blood flow is measured via laser Doppler flowmetry during cutaneous microdialysis perfusions of ET-A and ET-B receptor antagonists as previously described by Wenner MM in 2017(see reference list). | We were not able to recruit any hypertensive women naive to therapy for this arm of the study | Posted | Mean | Standard Error | % change blood flow flux | Each participant was assessed at baseline and 2 weeks later. |
|
Baseline and 2 weeks later
Standard definitions were used. No Adverse Events occurred.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normotensive | Normotensive PMW will complete an experimental visit to assess vascular function. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visit to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. Normotensive: FMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors. |
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We were not able to enroll naive to therapy hypertensive women for the Losartan arm of the trial and do not have data on this arm of the study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Megan Wenner | University of Delaware | 302-831-7343 | mwenner@udel.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 13, 2019 | Jan 17, 2022 | Prot_SAP_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 13, 2019 | Dec 11, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000959 | Antihypertensive Agents |
| ID | Term |
|---|---|
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
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|
| Hypertensives | Drug | ANG II increases the synthesis of ET-1 and alters ET-A/B receptor expression, thus affecting ET-1 bioavailability. Losartan is an ANG II receptor antagonist which attenuates ET-1 production. Losartan 50 mg daily is administered for 14 days to hypertensive women. FMD is used to measure endothelial function. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection. Laser Doppler flowmetry with cutaneous microdialysis is used to examine vascular function when ET-A and ET-B receptor antagonists is perfused via intradermal microdialysis fibers. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will be assessed. Skin punch biopsy samples will be used to assess for protein expression of ET-A and ET-B receptors. |
|
| Background |
| Barton M, Meyer MR. Postmenopausal hypertension: mechanisms and therapy. Hypertension. 2009 Jul;54(1):11-8. doi: 10.1161/HYPERTENSIONAHA.108.120022. Epub 2009 May 26. No abstract available. |
| 16910905 | Background | Kim JK, Alley D, Seeman T, Karlamangla A, Crimmins E. Recent changes in cardiovascular risk factors among women and men. J Womens Health (Larchmt). 2006 Jul-Aug;15(6):734-46. doi: 10.1089/jwh.2006.15.734. |
| 16914423 | Background | Yanes LL, Romero DG, Iles JW, Iliescu R, Gomez-Sanchez C, Reckelhoff JF. Sexual dimorphism in the renin-angiotensin system in aging spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2006 Aug;291(2):R383-90. doi: 10.1152/ajpregu.00510.2005. Epub 2006 Mar 30. |
| 20679182 | Background | Yanes LL, Romero DG, Iliescu R, Zhang H, Davis D, Reckelhoff JF. Postmenopausal hypertension: role of the Renin-Angiotensin system. Hypertension. 2010 Sep;56(3):359-63. doi: 10.1161/HYPERTENSIONAHA.110.152975. Epub 2010 Aug 2. |
| 11358929 | Background | Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001 May;37(5):1199-208. doi: 10.1161/01.hyp.37.5.1199. |
| 21509049 | Background | Yanes LL, Reckelhoff JF. Postmenopausal hypertension. Am J Hypertens. 2011 Jul;24(7):740-9. doi: 10.1038/ajh.2011.71. Epub 2011 Apr 21. |
| 15319224 | Background | Yanes LL, Romero DG, Cucchiarelli VE, Fortepiani LA, Gomez-Sanchez CE, Santacruz F, Reckelhoff JF. Role of endothelin in mediating postmenopausal hypertension in a rat model. Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R229-33. doi: 10.1152/ajpregu.00697.2003. Epub 2004 Aug 19. |
| 23220478 | Background | Lima R, Yanes LL, Davis DD, Reckelhoff JF. Roles played by 20-HETE, angiotensin II and endothelin in mediating the hypertension in aging female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2013 Feb;304(3):R248-51. doi: 10.1152/ajpregu.00380.2012. Epub 2012 Dec 5. |
| 7614809 | Background | Haynes WG. Endothelins as regulators of vascular tone in man. Clin Sci (Lond). 1995 May;88(5):509-17. doi: 10.1042/cs0880509. |
| 8197152 | Background | Ishikawa K, Ihara M, Noguchi K, Mase T, Mino N, Saeki T, Fukuroda T, Fukami T, Ozaki S, Nagase T, et al. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4892-6. doi: 10.1073/pnas.91.11.4892. |
| 2451132 | Background | Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411-5. doi: 10.1038/332411a0. |
| 15130882 | Background | Juan SH, Chen JJ, Chen CH, Lin H, Cheng CF, Liu JC, Hsieh MH, Chen YL, Chao HH, Chen TH, Chan P, Cheng TH. 17beta-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells. Am J Physiol Heart Circ Physiol. 2004 Sep;287(3):H1254-61. doi: 10.1152/ajpheart.00723.2003. Epub 2004 May 6. |
| 18188139 | Background | Pedersen SH, Nielsen LB, Mortensen A, Nilas L, Ottesen B. Progestins oppose the effects of estradiol on the endothelin-1 receptor type B in coronary arteries from ovariectomized hyperlipidemic rabbits. Menopause. 2008 May-Jun;15(3):503-10. doi: 10.1097/gme.0b013e318156f803. |
| 11488771 | Background | Wenzel RR, Ruthemann J, Bruck H, Schafers RF, Michel MC, Philipp T. Endothelin-A receptor antagonist inhibits angiotensin II and noradrenaline in man. Br J Clin Pharmacol. 2001 Aug;52(2):151-7. doi: 10.1046/j.0306-5251.2001.01422.x. |
| 15361762 | Background | Gossl M, Mitchell A, Lerman A, Opazo Saez A, Schafers RF, Erbel R, Philipp T, Wenzel RR. Endothelin-B-receptor-selective antagonist inhibits endothelin-1 induced potentiation on the vasoconstriction to noradrenaline and angiotensin II. J Hypertens. 2004 Oct;22(10):1909-16. doi: 10.1097/00004872-200410000-00013. |
| 11404288 | Background | Ballew JR, Fink GD. Role of ET(A) receptors in experimental ANG II-induced hypertension in rats. Am J Physiol Regul Integr Comp Physiol. 2001 Jul;281(1):R150-4. doi: 10.1152/ajpregu.2001.281.1.R150. |
| 9325182 | Background | Barton M, Shaw S, d'Uscio LV, Moreau P, Luscher TF. Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation. Biochem Biophys Res Commun. 1997 Sep 29;238(3):861-5. doi: 10.1006/bbrc.1997.7394. |
| 19706169 | Background | Dimitrijevic I, Edvinsson ML, Chen Q, Malmsjo M, Kimblad PO, Edvinsson L. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease. BMC Cardiovasc Disord. 2009 Aug 25;9:40. doi: 10.1186/1471-2261-9-40. |
| 8352786 | Background | Kanno K, Hirata Y, Tsujino M, Imai T, Shichiri M, Ito H, Marumo F. Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1282-7. doi: 10.1006/bbrc.1993.1962. |
| 9315552 | Background | Moreau P, d'Uscio LV, Shaw S, Takase H, Barton M, Luscher TF. Angiotensin II increases tissue endothelin and induces vascular hypertrophy: reversal by ET(A)-receptor antagonist. Circulation. 1997 Sep 2;96(5):1593-7. doi: 10.1161/01.cir.96.5.1593. |
| 19029977 | Background | Kobayashi T, Nogami T, Taguchi K, Matsumoto T, Kamata K. Diabetic state, high plasma insulin and angiotensin II combine to augment endothelin-1-induced vasoconstriction via ETA receptors and ERK. Br J Pharmacol. 2008 Dec;155(7):974-83. doi: 10.1038/bjp.2008.327. Epub 2008 Aug 18. |
| 14732213 | Background | Hong HJ, Chan P, Liu JC, Juan SH, Huang MT, Lin JG, Cheng TH. Angiotensin II induces endothelin-1 gene expression via extracellular signal-regulated kinase pathway in rat aortic smooth muscle cells. Cardiovasc Res. 2004 Jan 1;61(1):159-68. doi: 10.1016/j.cardiores.2003.10.019. |
| 1333547 | Background | Kohno M, Horio T, Ikeda M, Yokokawa K, Fukui T, Yasunari K, Kurihara N, Takeda T. Angiotensin II stimulates endothelin-1 secretion in cultured rat mesangial cells. Kidney Int. 1992 Oct;42(4):860-6. doi: 10.1038/ki.1992.361. |
| 28438762 | Background | Wenner MM, Sebzda KN, Kuczmarski AV, Pohlig RT, Edwards DG. ETB receptor contribution to vascular dysfunction in postmenopausal women. Am J Physiol Regul Integr Comp Physiol. 2017 Jul 1;313(1):R51-R57. doi: 10.1152/ajpregu.00410.2016. Epub 2017 Apr 24. |
| BG001 | Hypertensives | Hypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Hypertensives | Hypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. |
|
|
| Secondary | Endothelin Receptor A and B Expression | ET-A and ET-B receptors will be examined using immunocytochemistry from 3mm skin punch biopsy in women pre/post losartan administration. This Secondary aim was not complete due to difficulty with enrollment (no data collected in these groups). | Due to difficulty with enrollment we were not able to complete this outcome | Posted | Baseline and 2 weeks later |
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Hypertensives | Hypertensive women will be tested at baseline and then administered Losartan 50 mg once a day at night for 14 days. Vascular function is measured at baseline and again after 2 weeks of losartan. All women will wear an ambulatory BP monitor during the 24 hours preceding the experimental visits to confirm BP classification. Large blood vessel function will be assessed using two non-invasive techniques: 1. Flow Mediated Dilation (FMD) 2. Pulse Wave Analysis and Pulse Wave Velocity. ET-1 mediated vasoconstrictor tone is assessed by measuring the cutaneous blood flow during microdialysis perfusions of ET-A and ET-B receptor antagonist. ET-1 production, ET-A and ET-B receptor expression is assessed from antecubital vein endothelial cells and skin punch biopsy samples. | 0 | 0 | 0 | 0 | 0 | 0 |
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