Oxytocin, Prostaglandin F2α, and Prostaglandin E2 Induced Contractions in Isolated Uterine Smooth Muscle Strips from Non‐pregnant, Late Pregnant, and Postpartum Rats

Abstract

Objective/IntroductionNumerous studies have investigated uterotonic agents (e.g., oxytocin) in uterine smooth muscle (USM) from non‐pregnant (NP) and late‐pregnant (LP) women and/or animal models of pregnancy. Surprisingly, few studies have investigated USM from the post‐partum period to determine whether USM contractility returns to its pre‐pregnant state. We designed a study in rodents to investigate whether USM contractility to oxytocin (OXY), prostaglandin F2α (PGF2α), and prostaglandin E2 (PGE2) returned to pre‐pregnant values within 30 days postpartum.MethodsStudies were performed in NP (n=12), LP (21d gestation, n=4), 3 days post‐partum (PP3, n=2), and 30 days post‐partum (PP30, n=4) Sprague Dawley rats. Uterine horns were cleaned of connective tissue and cut along the longitudinal axis allowing isolation of USM (width: 2mm, length: 4±1mm) oriented in the longitudinal muscle (LM) or circular muscle (CM) direction. CM or LM strips were mounted in tissue baths containing Krebs and equilibrated @ 37°C for 60 min prior to starting one of the two following protocols.Protocol 1 identified the optimal resting tension (in grams: 0.25, 0.50, 1.0, and 1.5) to measure spontaneous contraction (SCA), K+‐induced contraction (60mM K+), and cumulative OXY‐induced contraction (10‐11 to 10‐7) in CM and LM of NP rats (N=4‐6).Protocol 2 was designed assess SCA, K+‐induced contraction, cumulative concentration‐response relationships to OXY (10‐11 to 10‐7), PGF2α (10‐8 to 10‐4), or PGE2 (10‐8 to 10‐4) in CM and LM, of NP, LP, PP3, and PP30 rats (N=2‐6).Statistical comparisons were made using either a t‐test or two‐way ANOVA, and considered statistically different at P<0.05.ResultsProtocol 1‐ LM SCA was greater than CM SCA at all resting tensions. K+‐induced constrictions in LM and CM were similar at each resting tension. OXY‐induced contraction in LM was generally greater than CM (P<0.05 at 0.25g, 0.5g, and 1.5g tension, comparable at 0.5, 1.0, and 1.5g tension).Protocol 2 ‐ SCA in NP, LM was greater than NP, CM (P<0.05). There was no difference in SCA in CM vs LM in USM from LP, PP3, and PP30 animals. K+‐induced constrictions in CM and LM were similar in USM from NP, LP, PP3 and PP30 animals. OXY‐induced contractions were greater in LM than CM for all pregnancy states (P<0.05). PGE2 contractions were greater in LM vs CM in USM from NP rats (P<0.05), but were similar in USM from LP, PP3, and PP30 animals. In contrast, PGF2α‐contractions were similar in LM and CM for all pregnancy states.Summary/ConclusionOur preliminary data suggests that uterotonic agents be assessed at either 0.5g or 1.0g resting tension. In addition, uterotonic agents exhibit significantly greater contraction in longitudinal vs circular orientation. Finally, contractility to uterotonic agents returns to pre‐pregnant values by PP30.