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Excitatory effect of oxytocin on uterine smooth muscle

Experiment for pharmacology for reproductive system. Excitatory effect of oxytocin on uterine smooth muscle. Shi-Hong Zhang （张世红） Dept of Pharmacology shzhang713@zju.edu.cn. Uterine stimulants. Pituitrin ( 垂体后叶素 ) Oxytocin ( 催产素 ) Ergot alkaloids ( 麦角生物碱 ) Prostaglandins (PGs, 前列腺素 ).

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Excitatory effect of oxytocin on uterine smooth muscle

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  1. Experiment for pharmacology for reproductive system Excitatory effect of oxytocin on uterine smooth muscle Shi-Hong Zhang （张世红）Dept of Pharmacologyshzhang713@zju.edu.cn

  2. Uterine stimulants • Pituitrin (垂体后叶素) • Oxytocin (催产素) • Ergot alkaloids (麦角生物碱) • Prostaglandins (PGs, 前列腺素)

  3. A. Uterine stimulants Pituitrin(垂体后叶素) • oxytocin • vasopressin

  4. Oxytocin (OXT, 催产素) Uterine stimulants 1. Pharmacological effects: (1) Uterus: Elevating both the frequency and force of uterine contraction, at rhythm similar to natural labor, highly dependent on estrogen level and condition of uterus. (2) Breast: milk ejection. (3) Blood vessel: vasodilation at large dose.

  5. Oxytocin (OXT, 催产素) Uterine stimulants 2. Clinical uses: -- to expedite delivery and induced labor; -- to reduce the incidence and extent of postpartum hemorrhage.

  6. Oxytocin (OXT, 催产素) Uterine stimulants 3. Adverse effects: -- Intrauterine asphyxia or uterine rupture (overdose) -- Allergy 4. Contraindications: --hypertonic dysfunction of uterus -- abnormality in birth canal -- abnormal fetal position

  7. Uterine stimulants Ergot alkaloids(麦角生物碱)Ergometrine(麦角新碱),Ergotamine(麦角胺), Ergotoxine(麦角毒) 1. Pharmacological effects: (1) Uterus (ergometrine): -- strongly stimulating uterine smooth muscle, both the body and the cervix; ready to induce tonic contraction at larger dose . (2) Blood vessel (ergotamine): -- contracting peripheral blood vessel and cerebral vessel. (3) blocking  receptor (ergotoxine):

  8. A. Uterine stimulants Ergot alkaloids(麦角生物碱) 2. Clinical uses: (1) Endometrorrhagia (子宫出血), and puerperal replacement of uterus (产后子宫复位) : ergometrine; (2) Migraine (偏头痛) : ergotamine; (3) Hibernation therapy (冬眠疗法) : dihydroergotoxine + pethidine + promethazine.

  9. A. Uterine stimulants Ergot alkaloids(麦角生物碱) 3. Adverse effects: -- nausea, vomiting, BP ; -- allergic reaction; -- prohibited in expediting delivery and induced labor.

  10. Uterine stimulants Prostaglandins (PGs, 前列腺素) Dinoprostone (地诺前列酮, PGE2) Dinoprost (地诺前列素,PGF2) 1. Pharmacological effect: stimulating uterine smooth muscle. 2. Clinical uses:toinduce labor 2. Adverse effects: GI reaction, attack of asthma (PGF2); glaucoma (PGE2).

  11. Objectives • To observe the excitatory effect of oxytocin on uterine smooth muscles and its dose dependent manner.

  12. Methods • Estrodiol pretreatment (0.2mg) on rats (200 g  40g) 24hr before experiment; • Prepare uterus smooth muscle specimen.

  13. Methods Uterus of the rat

  14. Methods Uterus of the rat

  15. Methods Perfusion system

  16. Methods • Set parameters of recording system: • Input pattern: tensility • Gain: 200-500 • Lower frequency: direct current • Upper frequency: 10 Hz • Sampling interval: 2 ms • Preload: 1g

  17. Methods • The specimen is stabilized in the perfusion chamber for 15-30 min until the contractive force and rhythm become regular. Record the basal contractive force and frequency (optional). • Add 0.02ml, 0.04ml, 0.14ml oxytocin (0.01U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly.

  18. Methods • Add 0.04ml, 0.14ml oxytocin (0.1U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly. • Add 0.04ml, 0.14ml oxytocin (1U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly.

  19. Methods • Add 0.04ml, 0.14ml oxytocin (10U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly.

  20. Methods Notice: 1．Avoid injury and excessive stretch of uterus during the whole process of preparation. 2．Control the gas bubbles in a proper rate in case of impact on uterus contraction. 3．Record a period of baseline of contraction before drug treatment in order to compare that before and after. 4．Add drug in the order as prescribed.

  21. Lab report 1．题目 2．署名: 作者和合作者姓名及单位。 3．结构式摘要（目的，方法，结果，结论）。 4．材料和方法: 主要实验材料，标本制备方法，仪器装置连接和仪器参数，实验数据记录条件，观察指标。 5．结果: 实验结果的文字性描述，作量效曲线。 6．讨论: 回答思考题。

  22. Learning issue 1．缩宫素对子宫的作用及特点。 2．为什么实验前用雌二醇处理动物？ 3. 缩宫素与麦角新碱对子宫平滑肌的作用特点有何不同？

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