1. Excitatory effect of oxytocin on uterine smooth muscle Shi-Hong Zhang （张世红） Dept of Pharmacology shzhang713@zju.edu.cn Experiment for pharmacology for reproductive system

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

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

4. Oxytocin (OXT, 催产素 ) 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. Uterine stimulants

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

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

7. 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): Uterine stimulants

8. 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. A. Uterine stimulants Ergot alkaloids( 麦角生物碱 )

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

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

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

12. Methods 1.Estrodiol pretreatment (0.2mg) on rats (200 g  40g) 24hr before experiment; 2.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 1.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). 2.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 3.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. 4.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 5.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？