Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes

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 degrees), secondary (UA 2 degrees), and tertiary (UA 3 degrees) 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 degrees eNOS levels were similar. There was a 60.7 +/- 9.8% reduction in eNOS expression in UA 2 degrees and UA 3 degrees. 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 degrees and UA 3 degrees. In UA 2 degrees and UA 3 degrees, 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 degrees and UA 3 degrees endothelial eNOS suggest a possible negative feedback mechanism due to downregulation of eNOS if SS is normalized.