Large Conductance Ca 2+ -Activated K + Channels Modulate Uterine α 1 -Adrenergic Sensitivity in Ovine Pregnancy

Abstract

The uteroplacental vasculature is refractory to α-adrenergic stimulation, and large conductance Ca²⁺-activated K⁺ channels (BK_Ca) may contribute. We examined the effects of uterine artery (UA) BK_Ca 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 %▵MAP 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 %▵UPVR>>%▵MAP, thus %▵UPBF fell. The TEA enhanced PE-mediated increases in %▵UPVR 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 BK_Ca activation, suggesting BK_Ca protect UPBF.