자료유형  

 학위논문

Control Number  

0017162912

International Standard Book Number  

9798384231288

Dewey Decimal Classification Number  

500

Main Entry-Personal Name  

Delgado, Jocelyn.

Publication, Distribution, etc. (Imprint  

[S.l.] : The Pennsylvania State University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

169 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-03, Section: A.

General Note  

Advisor: Proctor, David.

Dissertation Note  

Thesis (Ph.D.)--The Pennsylvania State University, 2024.

Summary, Etc.  

요약Differentiating the adverse chronological- and reproductive-aging associated changes on the vasculature remains a challenge to investigate. This is particularly important for women as the onset of menopause coincides with unfavorable changes to cardiovascular disease (CVD) risk factors. The permanent loss of estrogen following menopause is associated with reductions in nitric oxide bioavailability (NO), an important vasodilator and signaling molecule, which can lead to impaired endothelium-dependent vasodilation. Endothelial dysfunction, a prognostic indicator of CVD risk, rapidly declines across the menopause transition, independent of chronological age. To further understand the effects of reproductive aging on the vasculature, the first study of this dissertation compared the extent of vascular dysfunction from pneumatic cuff-induced whole arm endothelial ischemia-reperfusion (IR) injury in estrogen-replete premenopausal (n=11) and estrogen-deficient postmenopausal women staged into early- (1-6 years following menopause, n=11) and late- (6+ years following menopause, n=11) postmenopause. In this cross-sectional study, we found that despite comparable baseline endothelial function to premenopausal women, early postmenopausal women demonstrate an exaggerated IR-induced impairment in endothelial function.Few low risk-estrogen therapies exist for enhancing vascular health, and traditional pharmacological management of CVD risk factors are less effective in older women. Consequently, there is a clinical demand to investigate innovative non-pharmacological interventions, specifically nutraceuticals, focusing on dietary strategies that can enhance NO bioavailability in postmenopausal women. The subsequent study comprising this dissertation tested the ability of both acute (600 mg nitrate per 140 mL x one dose) and 7-day (300 mg nitrate per 70mL daily x 7 days) nitrate-rich beetroot juice supplementation to raise circulating concentrations of nitrite and favorably influence resting endothelial function, endothelial protection (i.e., endothelial resistance) against IR injury, and plasma oxidative stress (chapter 5) in normotensive, metabolically healthy early- (n=12) and late- (n=12) postmenopausal women. A randomized, placebo-controlled (BRnitrate vs. BRplacebo; IND#119978), double blind, crossover study design was used, with a minimum 14-day washout period between treatments and standardized pre-visit instructions to minimize between-visit variation in plasma nitrite concentration. Compared to responses observed with BRplacebo, our findings demonstrate: 1) acute BRnitrate consumption raised plasma nitrite concentration and improved endothelial resistance against IR injury, regardless of postmenopausal stage, 2) despite a clinically significant increase in resting endothelial function, nitrate-mediated endothelial protection against IR injury was not maintained 24-hours following the last dose of 7-day supplementation with BRnitrate in either postmenopausal group and 3) while 7-day BRnitrate did not affect the plasma metabolome, we show that reproductive aging critically impacts the plasma metabolite profile between postmenopausal stages. Collectively, these results provide the first evidence that acute dietary nitrate supplementation enhances endothelial protection against IR injury, regardless of postmenopausal stage. Moreover, our findings highlight that chronobiological variations in nitrate metabolism and the timing of BRnitrate supplementation in relation to the IR injury protocol, may have confounded the observed results following 7-day BRnitratesupplementation. These studies also raise a new series of questions related to the mechanisms by which dietary nitrate may benefit postmenopausal cardiovascular health and support the pursuit of larger scale trials of dietary nitrate supplementation to determine whether these effects are in fact clinically significant and sustainable.

Subject Added Entry-Topical Term  

Plasma.

Subject Added Entry-Topical Term  

Womens health.

Subject Added Entry-Topical Term  

Mortality.

Subject Added Entry-Topical Term  

Risk factors.

Subject Added Entry-Topical Term  

Antioxidants.

Subject Added Entry-Topical Term  

Atherosclerosis.

Subject Added Entry-Topical Term  

Drug dosages.

Subject Added Entry-Topical Term  

Oxidative stress.

Subject Added Entry-Topical Term  

Hormone replacement therapy.

Subject Added Entry-Topical Term  

Medicine.

Subject Added Entry-Topical Term  

Middle age.

Subject Added Entry-Topical Term  

Blood pressure.

Subject Added Entry-Topical Term  

Aging.

Subject Added Entry-Topical Term  

Hypertension.

Subject Added Entry-Topical Term  

Functional foods & nutraceuticals.

Subject Added Entry-Topical Term  

Cardiovascular disease.

Subject Added Entry-Topical Term  

Heart.

Subject Added Entry-Topical Term  

Ischemia.

Subject Added Entry-Topical Term  

Metabolites.

Subject Added Entry-Topical Term  

Angina pectoris.

Subject Added Entry-Topical Term  

Endocrinology.

Subject Added Entry-Topical Term  

Food science.

Subject Added Entry-Topical Term  

Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Public health.

Subject Added Entry-Topical Term  

Therapy.

Added Entry-Corporate Name  

The Pennsylvania State University.

Host Item Entry  

Dissertations Abstracts International. 86-03A.

Electronic Location and Access  

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Control Number  

joongbu:655578