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

R. Gracious Ross, K. Sathishkumar, Ajit Kumar Naik, Dnyaneshwar U. Bawankule, Souvendra N. Sarkar, Santosh K. Mishra, Vellanki Ravi Prakash

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)532-540
Number of pages9
JournalAmerican journal of obstetrics and gynecology
Volume190
Issue number2
DOIs
StatePublished - Feb 2004

Keywords

  • Ca influx
  • Lipopolysaccharide
  • Prostaglandins
  • Rat uterus
  • Sodium pump

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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