Transactions of the Sixty-Ninth Annual Meeting of the Central Association of Obstetricians and Gynecologists
Effects of recombinant human relaxin on pregnant rat uterine artery and myometrium in vitro

Presented at the Sixty-Ninth Annual Meeting of the Central Association of Obstetricians and Gynecologists, October 27-30, 2002, Las Vegas, Nev.
https://doi.org/10.1067/mob.2003.454Get rights and content

Abstract

Objective: The purpose of this study was to evaluate the effects of recombinant human relaxin on the uterine artery and myometrial contractility in pregnant rats. Study Design: Uterine artery and myometrial rings from mid and term pregnant rats were used. Relaxin effect was studied on phenylephrine-induced contraction in the presence or absence of nitric oxide synthase inhibitor, Nω- nitro-l-arginine methyl ester, soluble guanylate cyclase inhibitor, 1H-oxadiazolo-quinoxaline-1-one, or adenylate cyclase inhibitor, SQ-22,536. The myometrial inhibitory effect of relaxin was studied on spontaneous and oxytocin- or protein kinase C activator-induced contractions. Results: Uterine artery relaxation by relaxin was greater at mid pregnancy compared with term. Relaxin effect was decreased by SQ-22,536, 1H-oxadiazolo-quinoxaline-1-one and Nω- nitro-l-arginine methyl ester at mid pregnancy. Relaxin inhibited spontaneous contractions at mid pregnancy but not at term. Relaxin had no effect on oxytocin- or indolactam-V-induced contractions. Conclusion: Relaxin effect is mediated by nitric oxide, soluble guanylate cyclase, and adenylate cyclase in mid pregnant uterine artery. Relaxin inhibits spontaneous uterine activity at mid pregnancy. Relaxin effect decreased at term gestation in both tissues. (Am J Obstet Gynecol 2003;188:1468-76.)

Section snippets

Animals

Timed-pregnant Sprague-Dawley rats (200-250 g; Charles River Laboratories, Wilmington, Mass) at midgestation (day 14) and term (day 22) were used. The rats were given food and water ad libitum and were housed individually in temperature- and humidity-controlled quarters with automatic lighting that provided a 12-hour on-off cycle. The rats were killed by carbon dioxide inhalation on the day of the experiment. Each experimental group consisted of five to eight rats. The protocol for the animal

Results

Relaxin produced a concentration-dependent relaxation in the uterine artery rings from mid-pregnant rats (Fig 1).

. Responses in the uterine artery of midpregnant (open circles) and term (closed circles) pregnant rats to cumulative concentrations of relaxin. The preparations were precontracted with phenylephrine (PE, 10−7 to 10−6 mol/L). The Student t test was used. Asterisk, P <.05 versus term pregnant rats. Each point represents mean ± SEM; n = 5 to 8 rats.

The responses to relaxin in rings from

Comment

Circulating levels of relaxin are increased during pregnancy in rats.1 The levels of relaxin continue to rise with advancing gestation and then to decrease precipitously just before labor.1 These findings suggest a possible role for relaxin in the maintenance of pregnancy. In addition, its withdrawal may play a part in the multifactorial and complex process of labor. In this study, we have shown that relaxin is a potent dilator of the uterine artery. This is in agreement with previous studies

Acknowledgements

We thank Dr E. Unemori at Connetics Corporation, Palo Alto, Calif, for the supply of the recombinant human relaxin.

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    Reprint requests: R. E. Garfield, PhD, Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Texas Medical Branch, 301 University Blvd, Rt J-62, Galveston, TX 77555-1062.E-mail: [email protected]

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