Smooth Muscle Pharmacology in the Isolated Virgin and Pregnant Rat Uterus and Cervix

Abstract

Uterine smooth muscle function is established, but comparatively little is known about cervical smooth muscle pharmacology. We performed a proof-of-principle experiment that smooth muscle was expressed in the cervix in both virgin and pregnant rats, using the uterus as a comparator. We tested whether all tissues were pharmacologically responsive to contractile and relaxant agonists. Immunohistochemistry revealed the expression of smooth muscle ␣-actin in all tissues. The isolated tissue bath was used to measure isometric contractility of uterine strips and whole cervices from virgin and pregnant (day 11 Ϯ 2) female Sprague-Dawley rats. We tested classic activators of uterine smooth muscle contraction and relaxation in both uterus and cervix. All tissues contracted to the depolarizing agent potassium chloride, prostaglandin F2␣, muscarinic cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N-trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues, the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was present. Both cervix and uterus (virgin and pregnant) had concentration-dependent, near-complete relaxation to the adrenergic agonist norepinephrine and adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10 -10b-trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5-yl acetate]. The ␤-adrenergic receptor agonist isoproterenol was less potent in pregnant cervix versus virgin by ϳ10-fold. All tissues, particularly the cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing ϳ20% maximally. These findings support the importance of smooth muscle in the cervix, the use of the isolated cervix in pharmacological studies, and a similarity between smooth muscle pharmacology of the nonpregnant uterus and cervix. This work highlights the unappreciated smooth muscle function of the cervix versus uterus and cervical changes in pharmacology during pregnancy.

Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats

“…Different doses of agents were added to each strip sequentially and contractions measured. KCl (60 m m ) was also repeated at the end of the experiments to verify the viability of tissues during the course of the experiment (Darios et al., ). The CCh and OXY‐induced uterine contractions were assessed by changes in the amplitude of rhythmic contractions (maximal contraction minus basal resting tone, measured during a 10 min period of contraction after adding each dose of contractile agonist) and frequency of rhythmic contractions (the number of rhythmic contractions during a 10 min period of contraction after adding each dose of the contractile agonist).…”

“…The left uterine horn was placed in a dish containing ice-cold Krebs solution (mM: 11.90 NaHCO 3 , 2.13 MgCl 2 , 0.40 NaH 2 PO 4 , 139.97 NaCl, 3.00 KCl, 2.04 CaCl 2 and 5.05 glucose, pH 7.4) bubbled with 95% O 2 and 5% CO 2 . Longitudinal strips (∼3 mm × 10 mm) from each mid-horn region were dissected out and suspended in an organ bath containing 50 ml Krebs solution, and bubbled continuously with 95% O 2 and 5% CO 2 at 37 ± 0.5 • C. One end of the preparation was attached to a stainless-steel rod and the other end to a force transducer (MLT0202; ADInstruments, Spain), placed under a resting tension of 1 g and equilibrated for a period of 1 h (Darios, Seitz, & Watts, 2012). Changes in isometric force were recorded using an ADInstruments PowerLab (ML866; Australia).…”

Perubahan Histologis Uterus Tikus Putih (Rattus norvegicus) Galur Wistar: Aktifitas Antifertilitas Ekstrak Kulit Biji Mete (Anacardium occidentale L.)

“…Pemberian zat senobiotik tertentu pada tikus betina dapat menyebabkan uterotropik (meningkatnya berat uterus). Darios et al (2012) juga menyatakan kehamilan dapat terjadi bila struktur epitel endometrium dan otot-otot penyusun endometrium tidak mengalami perubahan.…”

Precocious cervical ripening as a screening target to predict spontaneous preterm delivery among asymptomatic singleton pregnancies: a systematic review

“…27, 37 Cervical pathophysiology has been further investigated through molecular and cellular approaches. 38–40 Romero and colleagues described cervical ripening as a general feature of the “premature parturition syndrome.” 41, 42 In 2011, routine recording of cervical ripening was recommended by the Global Alliance to Prevent Prematurity and Stillbirth. 43 In 2012, Caritis and Simhan proposed that the term PCCR was more appropriate and less confusing than either “cervical incompetence” 6, 44, 45 or “cervical insufficiency,” 46 both being ill-defined biologically.…”