Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation

Charles R. Rosenfeld, Blair E. Cox, Timothy Roy, Ronald R. Magness

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187 Scopus citations


Estradiol-17β (E2β), a potent vasodilator, has its greatest effects on the uterine vasculature, blood flow (UBF) increasing ≤ 10-fold. The mechanism(s) responsible for E2β-induced vasodilation is unclear. We determined if nitric oxide (NO)induced increases in cGMP modulate estrogen- induced increases in UBF, and if cyclooxygenase inhibition modifies E2β responses. Nonpregnant (n = 15) and pregnant (n = 8) ewes had flow probes implanted on main uterine arteries and catheters in branches of the uterine vein and artery bilaterally for blood sampling and infusion of the NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME), respectively. In nonpregnant ewes E2β (1 μg/kg) caused parallel increases (P < 0.001) in UBF (15±3 to 130±16 ml/min) and uterine cGMP secretion (23±10 to 291±38 pmol/min); uterine venous cGMP also rose (4.98±1.4 to 9.43±3.2 pmol/ml; P < 0.001). Intra-arterial L-NAME partially inhibited increases in UBF dose- dependently (r = 0.66, n = 18, P ≤ 0.003) while completely inhibiting cGMP secretion (P = 0.025). Indomethacin, 2 mg/kg intravenously, did not alter E2β-induced responses. After E2β-induced increases in UBF, intraarterial L-NAME partially decreased UBF dose dependently (r = 0.73, n = 46, P < 0.001) while inhibiting cGMP secretion (178±48 to 50±24 pmol/min; n = 5, P = 0.006); both were reversed by L-arginine. In pregnant ewes, E2β increased UBF and venous cGMP (9.1±0.96 to 13.2± 0.96 pmol/ml, P < 0.01); however, intraarterial L-NAME decreased basal cGMP secretion 66% (P = 0.02), but not UBF. Acute estrogen-induced increases in UBF are associated with NO- dependent increases in cGMP synthesis, but other mechanisms may also be involved. However, vasodilating prostanoids do not appear to be important. In ovine pregnancy NO is not essential for maintaining uteroplacental vasodilation.

Original languageEnglish (US)
Pages (from-to)2158-2166
Number of pages9
JournalJournal of Clinical Investigation
Issue number9
StatePublished - Nov 1 1996


  • blood flow
  • cGMP
  • indomethacin
  • pregnancy
  • sheep

ASJC Scopus subject areas

  • Medicine(all)


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