Regulation of types I and III NOS in ovine uterine arteries by daily and acute estrogen exposure

Walid A. Salhab, Philip W. Shaul, Blair E. Cox, Charles R. Rosenfeld

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Nitric oxide contributes to estrogen-mediated uterine vasodilation; however, the nitric oxide synthases (NOS) involved and their location within uterine arteries are incompletely documented. We investigated the effects of repetitive daily and acute estradiol-17β (E2β) exposure on uterine hemodynamics and NOS abundance and localization in uterine arteries from nonpregnant ovariectomized ewes receiving daily intravenous E2β (1 μ/kg, n = 5) or no E2β (n = 7) for 5 days to determine NOS abundance, cGMP contents, and NOS immunohistochemistry. Daily E2β increased basal and E2β-mediated rises in uterine blood flow (UBF) 36 and 43% (<0.01), respectively, calcium-dependent NOS activity 150% (P < 0.02) in endothelium- intact and -denuded (~40% of total NOS) arteries, and cGMP contents 39% (P < 0.05). Endothelial NOS (eNOS) was detected in luminal endothelium, whereas neuronal NOS (nNOS) protein was only in the media. A second group of ewes received E2β (1 μg/kg iv) for 4 days and acute intravenous E2β (n = 8) or vehicle (n = 4) on day 5. UBF rose 5.5-fold (P < 0.001) 115 min after E2β, at which time only endothelium-derived calcium-dependent NOS activity increased 30 ± 13% (P < 0.05). Daily E2β enhances basal and E2β-mediated increases in UBF, which parallel increases in endothelium-derived eNOS and smooth muscle-derived nNOS. Acute E2β, however, selectively increases endothelium-derived eNOS.

Original languageEnglish (US)
Pages (from-to)H2134-H2142
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 47-6
StatePublished - Jun 2000


  • Endothelium
  • Guanosine 3',5'- cyclic monophosphate
  • Guanylyl cyclase
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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