가토임신자궁의 Epinephrine 및 Norepinephrine에 대한 반응과 내인성 Catecholamine 함량
(The) sensitivity of pregnant rabbit uteri to epinephrine and norepinephrine and uterine catecholamine content
It has been known that norepinephrine and epinephrine, an neurohormonal transmitter, is synthesized and stored at the adrenergic nerve ending and that the uterus receives adrenergic terminals from the mesenteric ganglia. Many clinical studies to evaluate the action of these catecholamines in the pregnant uteri have been carried out since 1925 when Rucker first reported the diminished uterine contractions in the laboring patient by the use of epinephrine in combination with novocaine. Two years later, Bourne and Burn confirmed the fingind of decreased uterine contractions in labor following an intravenous drip of epinephrine, and Rucker also found that the injection of adrenaline causes a cessation of the uterine contractions and a relaxation of the constriction ring. Many investigators such as Rudolph and Ivy(1930), Ivy(1931), Irvins(1936), Titus(1937), Gunn(1942) and Garret(1954) have reported that epinephrine inhibits uterine contractions during pregnancy.
On the contrary, Wooldbury, Hamilton and Torpin(1938) reported that the injection of epinephrine stimulates the uterine contraction. Woodbury and Abru(1944) stressed that the effect of epinephrine on the uterus is entirely depend upon its concentration; in low concentration the uterine contraction are inhibited whereas in high concentration they are simulated. Kaiser and Harris(1950) confirmed the findings of Woodbury in 140 pregnant women. Telko(1960) reported that coordinated contractions can be produced by injection of norepinephrine and seems to be more effective on uterine contractions can be produced by injection of norepinephrine and seems to be more effective on uterine contractions than oxytocin. In recent years, Pose et al. have reported that the intravunous infusion of 1- epinephrine in labor showed a decrease in the intensity of the uterine contractions, and infusion on the 1-norepinephrine in labor produced a clear increase in the contractility of the uterus and the induced contractility had a significantly different pattern from the spontaneous or oxytocin-induced ones. Cha(1965) ahs found that the catecholamine concentration of the uterus become reduced during pregnancy, particularly at the placental site, and a small amount of norepinephrine(10^^7 M)
inhibits and a large amount stimulates the uterine activity wheres epinephrine always stimulates unterine ativity regardless the amount.
It is clear that many controversial opinions exist about the effect of epinephrine and norepinephrine on the pregnant uterus and there seems to be some relation between uterine catecholamine content and pregnancy. Therefore, the present study was undertaken to investigate uterine catecholamine content and uterine sensitivity to epinephrine and norepinephrine during pregnancy.
Materials and Methods
The experiments were conducted on the adult, female, albino rebbits subdivided into groups of non-pregnant, postpartum and reserpine treated. In all groups, uterine strips were prepared from the placental site, non-placental site and intersegmental bath (38℃) containing 100 ml. of Locke's solution aerated with 95% oxygen and 5% carbon dioxide. Spontanuous motility was recorded with as isotonic lever. The epinephrine and norepinephrine concentrations of the uteri were determined by the method of Shore and Olin(1958).
1. Non-pregnant: The effect of epinephrine on the non-pregnant uterine segment, during estrus, was stimulative to the uterine tonus and the sivilar effect was also observed with the norepinephrine. The effect of epinephrine on the dibenamine-treated uterine segment was inhibitory whereas the dichloroisoproterenol-treated uterine segment showed increased contractility.
Since the weight of the uterus varies with the preganacy, the total catecholamine content per uterus(mμg/uterus) could change even though the concentration of amines (mμg/g) could remain unaltered. For this reason, the amount of catecholamines per uterus and the amount per gram of uterus are both presented.
The catecholamine concentration of the non-preganant uterus was 331 mμg/g measuring 131 mμg/g of epinephrine and 200 mμg/g of norepinephrine, and the totla uterine contents of epinephrine and norepinephrine were 520 mμg/uterus and 810 mμg/uterus respectively, The norepinephrine, both in concentration and in totla content pr uterus, showed higher amount than that of the epinephrine.
2. Pregnant: In the pregnant uterine segments the effects of epinephrine and norepinephrine varied according to the period of pregnancy.
a) In early pregnancy (8-9 days), the uterine activity was inhibited by a low concentration of epinephrine or norepinephrine and, on the contrary, the uterine activity was stimulated by a higher concentration. The concentration of epinephrine and norepinephrine were 117 mμg/g and 60 mμg/g respectively and the total uterine contents were 931 mμg/uterus and 458 mμg/uterus respectively. The amount of norepinephrine becoame smaller than that of the epinephrine.
b) In mid-pregnancy(17-18 days), the effect of catecholamine on the uterine activity ws greater than that in early pregnancy. The catecholamine concentration.
however, was significantly decreased from the value of early pregnancy with marked reduction of the epinephrine. The epinephrine concentration was 46 mμg/g and norepinephrine was 51 mμg/g. The total uterine epinephrine content was 776 mμg/uterus, and total uterine norepinephrine was 846 mμg/uterus which was increased significantly
c) In late pregnancy(26-28 days), the effect of catecholamine on the uterine activity was markedly increased. The catecholamine concentration was also slightly increased over the value of mid-pregnancy as 50 mμg/g of epinephrine and 69 mμg/g of norepinephrine, The total coatecholamine content in this stage, however, showed the highest value of all during pregnancy such as 1047 mμg/uterus for the total epinephrine content and 1437 mμg/uterus for the norepinephrine contents.
3. Post-partum: the uterus soon after the delivery, the sensitivity of all uterine segments to the catecholamines showed a pattern similar to the late pregnancy. But in 24 hours or more after the delivery the uterine segment demonstrated decreased actiity and a tendency to return to normal. The catecholamine concentration was slightly higher than in late pregnancy; 71 mμg/g of epinephrine and 83 mμg/g of norepinephrine, but the total uterine contents were less thn that of the late pregnancy as the total epinephrine content was 980 mμg/uterus and the total norepinephrine was 1160 mμg/uterus.
4. Reserpine-treated: The sensitivity of the uterine segments prepared from the late pregnancy rabbits treated with repserpine (3 mg/kg intraperitoneally 24 hours before sacrifice) to the catecholamines ws diminished in general. A stimulation effect did occur only by a higher concentration(more than 10^^6 M) of the catechloamines while an inhibitory action was observed by the lower concentration. This sensitivity showed a pattern similar to the early pregnancy. The uterine catecholamines in this group were markedly reduced, particularly so for the norepinephrine content.
The uterine catecholamine concentration which is present in considerably high level in normal uterus was started to decrease in the early pregnancy, reached the lowest level in the mid-pregnancy and then started to increase again in the late pregnancy when the total catecholamine content become the highest level of all. This increase of catecholamine in late pregnancy in late pregnancy was chiefly due to the increase of norepinephrine. On the other hand, the effect of catecholamine on the uterine activity ws first inhibitory in the early pregnancy but became
gradually stimulative as the pregnancy progressed. This stimulating action on the uterine motility was found to occur through the action of norepinephrine.
It is suggestive that uterine motility may be related to the catecholamine content, especially norepinephrine, in the uterus.