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Perinatal Research Laboratories, 1 Departments of Obstetrics and Gynecology, 2 Pediatrics, and 3 Animal Sciences, University of Wisconsin, Madison, Wisconsin 53715
10.1152/ajpheart.00438.2001.
The follicular phase (FOL) and pregnancy
exhibit increases in uterine blood flow (UBF), estrogen levels, and
uterine artery (UA) endothelial nitric oxide synthase (eNOS)
expression. UA branching within the mesometrium increases the total
vascular cross-sectional area, which reduces the vascular perfusion
pressure gradient, thus locally decreasing the blood flow velocity.
Shear stress (SS) activates eNOS and may be associated with UBF
elevations during FOL and pregnancy. We hypothesized that regional
differences in eNOS responses are observed with both decreases in
vessel diameter and during the ovarian cycle and pregnancy. Endothelial
isolated proteins were collected from renal (RA) and internal iliac
arteries (II) as well as from primary (UA 1°), secondary (UA 2°),
and tertiary (UA 3°) UA branches of nonpregnant luteal phase (LUT;
n = 6) and FOL (n = 6) as well as
midpregnant (MP; 82 ± 1 days gestation, n = 6)
and late pregnant (LP; 127 ± 3 days gestation, n = 6) ewes (term = 145 ± 3 days gestation) for Western blot
analysis. LUT RA, II, and UA 1° eNOS levels were similar. There was a
60.7 ± 9.8% reduction in eNOS expression in UA 2° and UA 3°.
A similar decreasing eNOS regional expression gradient was observed in
LP ewes. No eNOS regional expression gradient was observed in FOL or MP
ewes because eNOS increased in UA 2° and UA 3°. In UA 2° and UA
3°, MP > LP = FOL > LUT. Thus, with increasing UBF,
FOL and pregnancy rises in SS may regulate eNOS protein expression in
smaller diameter UAs. A decrease in LUT and LP UA 2° and UA 3°
endothelial eNOS suggest a possible negative feedback mechanism due to
downregulation of eNOS if SS is normalized.
uterus; shear stress; endothelial nitric oxide synthase; ovarian; estrogen; progesterone
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