Control of blood flow to the gravid uterus of domestic livestock species
1995
Ford, S.P.
Uterine blood flow during pregnancy is controlled by two distinct phenomena: phasic contractility and tone. Phasic contractility, which mediates short-term contractions, functions through catecholamine activation of alpha 1-adrenergic receptors (AR), leading to hydrolysis of phosphatidylinositol 4, 6-bisphosphate (PIP2) to inositol triphosphate (IP3) and diacylglycerol (DAG). The phasic contractions proceed as IP3 stimulates the release of intracellular calcium stores that activate the calmodulin pathway, causing myosin filaments to slide past actin filaments; however, the contraction is quickly terminated via a reduction in free cytosolic calcium. A tonic contraction is initiated when the DAG generated during PIP2 hydrolysis binds to and activates protein kinase C (PKC) in the presence of increased cytosolic calcium. leading to shortening of the actin filaments. Concomitantly, stimulation of alpha 2-AR increases extracellular calcium uptake via the potential-sensitive channels (PSC), which potentiates activity of the membrane-bound PKC-DAG complexes, thus maintaining the degree of tonic contractility. Progesterone maintains the phasic contractility of uterine arterial smooth muscle throughout pregnancy by increasing alpha 1-AR numbers. Estrogens decrease uterine arterial tone (i.e., increase arterial diameter and flow) via their conversion to catechol estrogens by peroxidase in uterine lymphatic fluid. Catechol estrogens directly inhibit calcium uptake through PSC, resulting in a reduced activity of membrane-bound PKC-DAG complexes.
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