NITRIC-OXIDE CONTRIBUTES TO ESTROGEN-INDUCED VASODILATION OF THE OVINE UTERINE CIRCULATION

Estradiol-17 beta (E(2) beta), a potent vasodilator, has its greatest effects on the uterine vasculature, blood flow (UBF) increasing greate r than or equal to 10-fold. The mechanism(s) responsible for E(2) beta -induced vasodilation is unclear. We determined if nitric oxide (NO)in duced increases in cGMP modulate estrogen-induced increases in UBF, an d if cyclooxygenase inhibition modifies E(2) beta responses. Nonpregna nt (n = 15) and pregnant (n = 8) ewes had flow probes implanted on mai n uterine arteries and catheters in branches of the uterine vein and a rtery bilaterally for blood sampling and infusion of the NO synthase i nhibitor L-nitro-arginine methyl ester (L-NAME), respectively. In nonp regnant ewes E(2) beta (1 mu g/kg) caused parallel increases (P < 0.00 1) 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 in hibited increases in UBF dose-dependently (r = 0.66, n = 18, P less th an or equal to 0.003) while completely inhibiting cGMP secretion (P = 0.025). Indomethacin, 2 mg/kg intravenously, did not alter E(2) beta-i nduced responses. After E(2) beta-induced increases in UBF, intraarter ial 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, E(2) beta 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 inc reases in UBF are associated with NO-dependent increases in cGMP synth esis, but other mechanisms may also be involved. However, vasodilating prostanoids do not appear to be important. In ovine pregnancy NO is n ot essential for maintaining uteroplacental vasodilation.