TY - JOUR
T1 - Large conductance Ca2+-activated K+ channels modulate uterine α1-adrenergic sensitivity in ovine pregnancy
AU - Rosenfeld, Charles R.
AU - Hynan, Linda S.
AU - Liu, Xiao Tie
AU - Roy, Timothy
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by R01-HD008783-36 (CRR) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the George L. MacGregor Professorship in Pediatrics . The content is the responsibility of the authors and does not represent views of Eunice Kennedy Shriver National Institute of Child Health & Human Development and NIH .
PY - 2014/4
Y1 - 2014/4
N2 - The uteroplacental vasculature is refractory to α-adrenergic stimulation, and large conductance Ca2+-activated K+ channels (BKCa) may contribute. We examined the effects of uterine artery (UA) BKCa inhibition with tetraethylammonium (TEA) on hemodynamic responses to phenylephrine (PE) at 101 to 117 days and 135 to 147 days of ovine gestation, obtaining dose responses for mean arterial pressure (MAP), heart rate (HR), and uteroplacental blood flow (UPBF) and vascular resistance (UPVR) before and during UA TEA infusions. The UA α1-adrenergic receptors (α1-ARs) were assessed. The PE increased MAP and UPVR and decreased HR and UPBF dose dependently at both gestations (P <.001, analysis of variance). The %δMAP was less at 135 to 147 days before and during TEA infusions (P ≤.008); however, responses during TEA were greater (P ≤.002). The PE increased %δUPVR>>%δMAP, thus %δUPBF fell. The TEA enhanced PE-mediated increases in %δUPVR at 135 to 147 days (P ≤.03). The UA α1-AR expression was unchanged in pregnancy. Uterine vascular responses to PE exceed systemic vascular responses throughout pregnancy and are attenuated by BKCa activation, suggesting BKCa protect UPBF.
AB - The uteroplacental vasculature is refractory to α-adrenergic stimulation, and large conductance Ca2+-activated K+ channels (BKCa) may contribute. We examined the effects of uterine artery (UA) BKCa inhibition with tetraethylammonium (TEA) on hemodynamic responses to phenylephrine (PE) at 101 to 117 days and 135 to 147 days of ovine gestation, obtaining dose responses for mean arterial pressure (MAP), heart rate (HR), and uteroplacental blood flow (UPBF) and vascular resistance (UPVR) before and during UA TEA infusions. The UA α1-adrenergic receptors (α1-ARs) were assessed. The PE increased MAP and UPVR and decreased HR and UPBF dose dependently at both gestations (P <.001, analysis of variance). The %δMAP was less at 135 to 147 days before and during TEA infusions (P ≤.008); however, responses during TEA were greater (P ≤.002). The PE increased %δUPVR>>%δMAP, thus %δUPBF fell. The TEA enhanced PE-mediated increases in %δUPVR at 135 to 147 days (P ≤.03). The UA α1-AR expression was unchanged in pregnancy. Uterine vascular responses to PE exceed systemic vascular responses throughout pregnancy and are attenuated by BKCa activation, suggesting BKCa protect UPBF.
KW - pressor responses
KW - uteroplacental blood flow
KW - vascular sensitivity
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U2 - 10.1177/1933719113503409
DO - 10.1177/1933719113503409
M3 - Article
C2 - 24026311
AN - SCOPUS:84898978423
SN - 1933-7191
VL - 21
SP - 456
EP - 464
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 4
ER -