Mechanisms of lipopolysaccharide-induced changes in effects of contractile agonists on pregnant rat myometrium

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Abstract

Objective

The study was undertaken to investigate the mechanisms underlying enhanced uterine contractility induced by lipopolysaccharide (LPS) in pregnant rats.

Study design

Wistar rats were administered intrauterine either LPS (50 μg) or normal saline solution (0.05 mL) on day 17 of gestation. On day 19, the animals were killed and uterus was isolated for isometric recording, 45Ca++ influx measurement, and determination of plasma membrane Na+-K+-ATPase.

Results

Uterine strips, taken from LPS-treated rats, displayed a marked increase in amplitude of spontaneous rhythmic contractions compared with controls. Enhancement in the sensitivity of uterine strips to agonists such as oxytocin, 5-hydroxytryptamine (5-HT), and BAY K8644 was also observed in rats treated with LPS. Cyclo-oxygenase-2 inhibitor, nimesulide (10 μmol/L) had no significant effect on the LPS-induced increase in spontaneous rhythmic contractions. On the other hand, nimesulide attenuated the increased sensitivity of uterine strips to oxytocin induced by LPS. Nimesulide significantly inhibited 5-HT–induced uterine contractions in both control and LPS-treated rats. However, the enhanced sensitivity of uterine strips to 5-HT was evident even in the presence of nimesulide in rats treated with LPS. Nifedipine-sensitive 45Ca++-influx into uterine strips both in the basal state as well as those stimulated by high K+ (80 mmol/L) and 5-HT (1 μmol/L) was greater in LPS-treated group compared with the controls. LPS treatment caused a marked inhibition in the Na+-K+-ATPase activity of the uterine plasma membrane compared with controls. LPS had no effect on plasma 17β-estradiol levels.

Conclusion

LPS appears to increase uterine contractility of pregnant rats both through the release of endogenous prostaglandins and increased influx of Ca++ through L-type Ca++ channels. Inhibition of sodium pump by LPS may be an additional mechanism in augmentation of uterine excitability.

Section snippets

Administration of LPS

Adult female Wistar rats (150-200 g), obtained from the Laboratory Animal Resource Section, Indian Veterinary Research Institute, Izatnagar, were used in this study as per the Institutional Policy on Animal Use. Pregnancy was confirmed (designated as day 1 of gestation) by the presence of sperms in the vaginal smear. On day 17 of gestation, laparotomy was conducted in all rats under ketamine anesthesia (100 mg/kg body weight intramuscularly). LPS (Escherichia coli serotype 055:B5,

Effect of LPS on spontaneous rhythmic contractions of pregnant rat uterus

Figure 1, A, shows the recording of spontaneous rhythmic contractions of uterine strips, isolated from normal saline solution–treated (control) and LPS-treated pregnant rats, LPS treatment significantly (P<.05) increased the amplitude of spontaneous rhythmic contractions compared with controls, although maximal effects did not differ significantly (Table). LPS, however, had no effect on the frequency of rhythmic contractions (Figure 1, C).

Effect of LPS on uterine contractions induced by oxytocin, 5-HT, carboprost, and BAY K8644

Figure 2, A, depicts the effect of intrauterine

Comment

The most important observations of this study are as follows: (1) intrauterine LPS treatment enhanced spontaneous rhythmic contractions and contractions elicited with oxytocin, 5-HT, and BAY K8644 in isolated uteri obtained from the 19-day pregnant rats, (2) LPS-treatment, however, had no effect on contractions elicited with carboprost, (3) nimesulide failed to attenuate the increased rhythmic contractions induced by LPS; however, it antagonized the increased sensitivity of uterine strips to

References (25)

  • M Nakano et al.

    The contractility of uterine smooth muscle from pregnant rats infected intraperitoneally

    Acta Obstet Gynecol Jpn

    (1994)
  • Y Katsuki et al.

    Ability of intrauterine bacterial lipopolysaccharide to cause in situ uterine contractions in pregnant rabbits

    Acta Obstet Gynecol Scand

    (1997)
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