Vascular Dysfunction in Hypertensive Postmenopausal Women

Summary

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.

Timeline

Start

2017-09-01

Primary completion

2019-12-31

Completion

2019-12-31

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Background Haynes WG. Endothelins as regulators of vascular tone in man. Clin Sci (Lond). 1995 May;88(5):509-17. doi: 10.1042/cs0880509.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
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• 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.
• 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.
• 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.
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• 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.

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