Cardiovascular disease (CVD) is the leading cause of death in women, and mortality from CVD is higher in postmenopausal women (PMW) compared to age-matched men. PMW are at a greater risk for developing hypertension (HTN), a major risk factor for CVD. Furthermore, PMW are more likely to have uncontrolled or resistant HTN despite medication. Functional changes in the microcirculation can be used as an index of future CVD risk; the mechanisms contributing to microvascular dysfunction can be easily assessed using the cutaneous circulation. Endothelin-1 (ET-1) is a potent vasoconstrictor that has been implicated in the development of HTN, and data in animal models indicates ET-1 receptors are modulated by hormones like estradiol and angiotensin II (ANG II).
The first aim of this project is to test the hypothesis that ET-1 contributes to vasoconstriction in hypertensive PMW and that ANG II exacerbates the effects of ET-1.
The second aim of this project is to test the hypothesis that ET-1 expression along with ET-A and ET-B receptor expression are altered in hypertensive PMW. Our 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 ETA and ETB receptors on vascular smooth muscle. We further hypothesize that ANG II exacerbate the increase in ET-1, and the cellular changes ET-A and ET-B receptor expression contribute to the exaggerated constriction with HTN in PMW. We will test our central hypothesis by measuring changes in cutaneous blood flow during intradermal microdialysis infusions of ET-A and ET-B receptor antagonists in normotensive PMW and hypertensive PMW before and after losartan. Endothelial cells and skin punch biopsies will also be obtained directly from normotensive and hypertensive PMW (pre/post losartan) to examine cellular expression of ET-1 and ET-A and ET-B receptors. This comprehensive assessment of ET-1 receptor responses will provide novel information on the mechanisms contributing to vascular dysfunction in hypertensive PMW. Because CVD is the leading cause of death in women and PMW have a higher prevalence of HTN and mortality from CVD, understanding the mechanisms contributing to this higher prevalence in women is of both physiological and clinical importance to develop future preventative and therapeutic strategies for women.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Delaware
United States
Zip Code
Patterson, Freda; Grandner, Michael A; Lozano, Alicia et al. (2018) Transitioning from adequate to inadequate sleep duration associated with higher smoking rate and greater nicotine dependence in a population sample. Addict Behav 77:47-50
Patterson, Freda; Lozano, Alicia; Huang, Liming et al. (2018) Towards a demographic risk profile for sedentary behaviours in middle-aged British adults: a cross-sectional population study. BMJ Open 8:e019639
Patterson, Freda; Malone, Susan Kohl; Grandner, Michael A et al. (2018) Interactive effects of sleep duration and morning/evening preference on cardiovascular risk factors. Eur J Public Health 28:155-161
Robson, Shannon M; Lozano, Alicia J; Papas, Mia et al. (2017) Food Insecurity and Cardiometabolic Risk Factors in Adolescents. Prev Chronic Dis 14:E110
Tremblay, Mark S; Aubert, Salomé; Barnes, Joel D et al. (2017) Sedentary Behavior Research Network (SBRN) - Terminology Consensus Project process and outcome. Int J Behav Nutr Phys Act 14:75
Lenhart, Clare M; Wiemken, Andrew; Hanlon, Alexandra et al. (2017) Perceived neighborhood safety related to physical activity but not recreational screen-based sedentary behavior in adolescents. BMC Public Health 17:722
Patterson, Freda; Zaslav, David S; Kolman-Taddeo, Diana et al. (2017) Smoking Cessation in Pulmonary Care Subjects: A Mixed Methods Analysis of Treatment-Seeking Participation and Preferences. Respir Care 62:179-192
Wenner, Megan M; Sebzda, Kelly N; Kuczmarski, Andrew V et al. (2017) ETB receptor contribution to vascular dysfunction in postmenopausal women. Am J Physiol Regul Integr Comp Physiol 313:R51-R57
Nair, Uma S; Patterson, Freda; Rodriguez, Daniel et al. (2017) A telephone-based intervention to promote physical activity during smoking cessation: a randomized controlled proof-of-concept study. Transl Behav Med 7:138-147
Wright, Regina S; Gerassimakis, Constance; Bygrave, Desirée et al. (2017) Dietary Factors and Cognitive Function in Poor Urban Settings. Curr Nutr Rep 6:32-40

Showing the most recent 10 out of 18 publications