Effects of the ovary and conceptus on uterine blood flow in the pig

Abstract

Summary. Changes in uterine blood flow throughout pregnancy appear to be due to steroid-induced alterations in uterine arterial tone and contractility. Arterial contractility is a transient reduction in luminal diameter in response to nerve stimulation or to an alpha-1 adrenergic agonist, leading to short-term reduction in uterine blood flow. Tone is the pressure exerted by an arterial segment against an intraluminal flow (distensibility) and is considered to set the baseline rate of flow. These phenomena appear to be regulated individually, with tone changes predominating during pregnancy. In pregnancy, tone is markedly depressed as oestrogen concentrations rise, and the vessel is distended and flaccid. Arterial tone is a function of the amount of calcium available to the contractile proteins of the arterial smooth muscle, which is derived from extracellular sources. Calcium availability is regulated by the opening and closing of calcium channels in the surface membrane in response to changes in the membrane potential. The loss of uterine arterial tone associated with oestrogen results from a markedly depressed uptake of calcium by the vessels. A significant negative correlation (P < 0.001; r = – 0.93) is observed between uterine arterial uptake of calcium and the concentrations of oestrogens in systemic blood of pigs throughout gestation. Several lines of evidence suggest that the blockade of potential-sensitive calcium channels associated with uterine hyperaemia is produced by catechol oestrogens, short-lived metabolites of oestrogens that are found in the circulation when oestrogen levels are high. Synthesis of catechol oestrogens from the parent oestrogens has been shown to occur in the placenta, endometrium and uterine arteries of pigs. In addition, perfusion of uterine arteries from nonpregnant pigs with catechol oestrogens, but not free oestrogens, in vitro significantly reduces both the tone and the uptake of calcium by the vessels. Contractility of the arteries to nerve stimulation or phenylephrine, however, is not affected. These data suggest that the pig conceptus, through production of catechol oestrogens, locally increases arterial distensibility, resulting in increased baseline flow to each fetal—placental unit. The contractility (reactivity) of the uterine arterial vasculature to adrenergic agonists or other vasoactive agents, however, is not affected. In this way, the conceptus can maintain the locally elevated flows necessary for its survival while the maternal system can continue to respond to life-threatening stimuli by transiently rerouting blood flow away from the uterus and towards other vascular beds more necessary for maternal survival.