Author ORCID Identifier

0000-0001-8677-5912

Date of Award

Summer 8-9-2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Kinesiology and Health

First Advisor

Brett J. Wong

Second Advisor

Jeffrey Otis

Third Advisor

Christopher Ingalls

Fourth Advisor

Rafaela Feresin

Fifth Advisor

Anna Stanhewicz

Abstract

Endothelial function is an indicator and predictor of cardiovascular health. Mechanisms of endothelial function in premenopausal women remain unclear, including across hormonal state or phase, as well as in comparison with men. This dissertation includes four projects assessing cutaneous microvascular and endothelial function. The overall purpose is to investigate mechanisms of endothelial function and nitric oxide (NO) bioavailability in premenopausal women, with a specific focus on the impact of monophasic, combined oral contraceptive pills (OCP). Major findings are as follows. 1) During respective low hormone (LH) phases, NO-dependent dilation is greater in women using OCP (74±11 %NO) than naturally cycling (NC) women (NC women, 52±14 %NO; ppmax; high hormone, HH: 56±25 %CVCmax). 3) OCP phase affects mechanisms underlying endothelial function (p=0.03), primarily an interaction between the NO (control LH, 72±13 %NO; control HH, 62±16 %NO) and cyclooxygenase (COX; COX inhibition LH, 63±19 %NO; COX inhibition HH, 75±12 %NO) pathways. Further, women using OCP may have a greater interdependence on endothelial-derived hyperpolarizing factors to elicit vasodilation (65-69%) than previously reported findings in young, mixed-sex cohorts. 4) Women using OCP demonstrate a basal presence of COX-derived vasoconstrictors (baseline: control, 16±10 %CVCmax; COX inhibition, 27±11 %CVCmax), previously not demonstrated in young, mixed-sex cohorts. 5) A case study revealed OCP use may reduce endothelial function, demonstrated by substantially improved endothelium-dependent vasodilation following OCP cessation (during use: 42±10 %CVCmax; after cessation: 63±10 %CVCmax). Collectively, these data suggest women in LH phases of the natural menstrual cycle and various exogenous hormone states may not have equivalent endothelial function, which is important for experimental design. Additionally, these data suggest the withdrawal of exogenous hormones (i.e., the OCP LH phase or cessation of use) improves endothelial function and/or NO bioavailability. Therefore, OCP use appears to alter mediating mechanisms in the vasculature, which may contribute to cardiovascular health in women.

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