EVIDENCE FOR DECLINING EXTRACELLULAR CALCIUM-UPTAKE AND PROTEIN-KINASE-C ACTIVITY IN UTERINE ARTERIAL SMOOTH-MUSCLE DURING GESTATION IN GILTS

Uterine arterial blood flow and uterine arterial diameter are known to increase dramatically and progressively throughout gestation. Previous data from our laboratory have demonstrated that the KCl-induced membrane depolarization of uterine arterial smooth muscle specifically induces Ca2+ uptake through the potentially sensitive channels (PSC). Evidence from other laboratories suggests that calcium uptake through the PSC mediates long-term changes in uterine arterial diameter and flow (tone), possibly through activation of protein kinase C (PKC). In study 1 we evaluated uterine arteries removed from gilts on Days 20, 50, 80, and 110 of gestation for their ability to take up extracellular Ca2+ and to contract in response to a depolarizing dose of KCl. The ability of KCl to induce contraction of uterine arteries as well as its ability to stimulate extracellular Ca-45(2+) uptake by these same arteries declines (p < 0.01) progressively from Day 20 through Day 110 of gestation. Estrogen concentrations in systemic blood were negatively correlated with the contractile response (r = -0.57; p < 0.01) and extracellular Ca-45(2+) uptake (r = -0.93; p < 0.0001) of uterine arteries during gestation. In study 2 we evaluated changes in uterine arterial PKC and protein kinase M (PKM) throughout the estrous cycle and gestation. It was determined that cytosolic PKC declined with the advancement of gestation whereas PKM progressively increased (r = -0.63; p < 0.01). These data suggest a decreasing ability of the uterine artery to take up extracellular Ca2+ through the PSC as gestation advances, in association with decreasing cytosolic PKC.