Regulating Vascular Endothelial Function in Postmenopausal Women

By Jaycee Alban

Postmenopausal women (PMW) exhibit reduced endothelial function

compared to younger, premenopausal women (YW). This is mainly attributed to the

loss of estrogen with menopause but the mechanisms underlying the decline in

endothelial function remain unclear. Angiotensin-(1-7) Ang-(1-7)] induces

vasodilation through the Mas receptor (MasR) and has been shown to restore

endothelium-dependent dilation in women with endothelial dysfunction. Animal

studies suggest menopause and aging reduce vascular sensitivity to Ang-(1-7) which

may cause a compensatory upregulation of MasR. However, the role of the Ang-(1-7)/

MasR axis has not yet been studied in humans. The central hypothesis of this was

that the Ang-(1-7)/MasR axis is a main regulator of vascular function in women and

that there is dysfunction in this pathway that occurs during menopause which leads to

the pathologies associated with the onset of CVD. We hypothesize that PMW would

have decreased vascular sensitivity to Ang-(1-7), local administration of Ang-(1-7)

would improve endothelial function, and PMW would show a compensatory-based

upregulation of MasR on endothelial cells. Methods: Blood flow was measured using

laser Doppler flowmetry. To assess vascular sensitivity, Ang-(1-7) was locally

administered in escalating doses in the presence and absence of L-NAME via

cutaneous microdialysis to elicit a dose-dependent response. Dose response curves

were fit to a sigmoidal curve and the ED50, slope, area under the curve, and peak

response were compared between groups. To assess endothelial function, local

heating of the cutaneous circulation to 42C - which elicits an endothelium-dependent dilation - was performed during microdialysis perfusions of

lactated Ringers (control) or Ang-(1-7). All skin blood flow data are expressed as

cutaneous vascular conductance as a percentage of the maximum dilation elicited by

sodium nitroprusside perfusions with heating to 43����C (CVC%max). Separately,

venous endothelial cells were collected from PMW and YW and stained for MasR

using immunocytochemistry and are expressed as protein expression arbitrary units

(A.U.) following normalization to a positive control. All data are presented as

mean+SD and alpha was set to P

older than YW and showed elevated diastolic blood pressure, total cholesterol, LDL

cholesterol, HDL cholesterol, and blood glucose that is characteristic with aging and

menopause in this population. There were no differences in the dose-dependent

response to Ang-(1-7) (Top: (YW: 99.93+17.32 vs. PMW: 97.58+31.32), LogED50

(YW: 9.34+10.5 vs PMW: 8.40+3.96), HillSlope (YW: 0.18+0.24 vs PMW:

0.25+0.21), or area under the curve (YW: 73.76+19.83, vs PMW: 67.35+12.01);

p>0.05 for all variables). There was also no significant difference in NO-dependent

dilation to Ang-(1-7) between YW and PMW (YW: 7.56+26.36 AUC vs. PMW:

17.40+25.75 AUC; p=0.48). PMW displayed a blunted endothelial function shown by

a significantly attenuated response to local heating in the control site (YW: 91.26+4.87

CVC%max vs. PMW: 85.97+5.63 CVC%max; p=0.03), however, there was no impact of

Ang-(1-7) on the response to local heating in either group (YW: 89.23+10.35

CVC%max vs. PMW 87.19+9.57 CVC%max; p=0.88). Lastly, there were no differences

in endothelial MasR expression between groups (YW: 0.36+0.08 A.U

• Format: Paperback
• Language: English
• ISBN: B0F6V7TLJN
• ISBN13: 9798349312335
• Release Date: April 2025
• Publisher: Infotech
• Length: 124 Pages
• Weight: 0.39 lbs.
• Dimensions: 0.3" x 6.0" x 9.0"