TY - JOUR
T1 - Calcium-activated potassium channels and nitric oxide coregulate estrogen-induced vasodilation
AU - Rosenfeld, Charles R.
AU - White, Richard E.
AU - Roy, Tim
AU - Cox, Blair E.
PY - 2000
Y1 - 2000
N2 - Nitric oxide synthase (NOS) contributes to estradiol-17β (E2β)-induced uterine vasodilation, but additional mechanisms are involved, and the cellular pathways remain unclear. We determined if 1) uterine artery myocytes express potassium channels, 2) E2β activates these channels, and 3) channel blockade plus NOS inhibition alters E2β-induced uterine vasodilation. Studies of cell-attached patches identified a 107 ± 7 pS calcium-dependent potassium channel (BK(Ca)) in uterine artery myocytes that rapidly increased single-channel open probability 70-fold (P < 0.05) after exposure to 100 nM E2β through an apparent cGMP-dependent mechanism. In ovari-ectomized nonpregnant ewes (n = 11) with uterine artery flow probes and catheters, local BK(Ca) blockade with tetraethylammonium (TEA; 0.05-0.6 mM) dose dependently inhibited E2β-induced uterine vasodilation (n = 37, R = 0.77, P < 0.0001), with maximum inhibition averaging 67 ± 11%. Mean arterial pressure (MAP) and E2β-induced increases (P ≤ 0.001) in heart rate (13%) and contralateral uterine blood flow (UBF, ~5-fold) were unaffected. Local NOS inhibition plus BK(Ca) blockade, using submaximal doses of nitro-L-arginine methyl ester (5 mg/ml) and TEA (0.3 mM), did not alter basal UBF but completely inhibited ipsilateral E2β-induced uterine vasodilation without affecting MAP and E2β-induced increases in contralateral UBF and heart rate. Acute E2β-mediated uterine vasodilation involves rapid activation of uterine artery BK(Ca) and NOS, and the pathway for their interaction appears to include activation of guanylyl cyclase.
AB - Nitric oxide synthase (NOS) contributes to estradiol-17β (E2β)-induced uterine vasodilation, but additional mechanisms are involved, and the cellular pathways remain unclear. We determined if 1) uterine artery myocytes express potassium channels, 2) E2β activates these channels, and 3) channel blockade plus NOS inhibition alters E2β-induced uterine vasodilation. Studies of cell-attached patches identified a 107 ± 7 pS calcium-dependent potassium channel (BK(Ca)) in uterine artery myocytes that rapidly increased single-channel open probability 70-fold (P < 0.05) after exposure to 100 nM E2β through an apparent cGMP-dependent mechanism. In ovari-ectomized nonpregnant ewes (n = 11) with uterine artery flow probes and catheters, local BK(Ca) blockade with tetraethylammonium (TEA; 0.05-0.6 mM) dose dependently inhibited E2β-induced uterine vasodilation (n = 37, R = 0.77, P < 0.0001), with maximum inhibition averaging 67 ± 11%. Mean arterial pressure (MAP) and E2β-induced increases (P ≤ 0.001) in heart rate (13%) and contralateral uterine blood flow (UBF, ~5-fold) were unaffected. Local NOS inhibition plus BK(Ca) blockade, using submaximal doses of nitro-L-arginine methyl ester (5 mg/ml) and TEA (0.3 mM), did not alter basal UBF but completely inhibited ipsilateral E2β-induced uterine vasodilation without affecting MAP and E2β-induced increases in contralateral UBF and heart rate. Acute E2β-mediated uterine vasodilation involves rapid activation of uterine artery BK(Ca) and NOS, and the pathway for their interaction appears to include activation of guanylyl cyclase.
KW - Estradiol-17β
KW - Nonpregnant sheep
KW - Uterine blood flow
UR - http://www.scopus.com/inward/record.url?scp=0033853512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033853512&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2000.279.1.h319
DO - 10.1152/ajpheart.2000.279.1.h319
M3 - Article
C2 - 10899072
AN - SCOPUS:0033853512
SN - 0363-6135
VL - 279
SP - H319-H328
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1 48-1
ER -