1. Excitatory effect of uterine stimulants on uterine smooth muscle Shi-Hong Zhang （张世红） Dept of Pharmacology shzhang713@zju.edu.cn Experimental pharmacology of 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 血管加压素 (ADH) Uterine stimulants

4. Oxytocin (OXT, 催产素 ) Uterine stimulants Vincent du Vigneaud (1901-1978, USA) Won Nobel prize in Chemistry in 1955 for isolation and synthesis of oxytocin

5. Oxytocin (OXT, 催产素 ) 1. Pharmacological effects: (1) Uterus: Stimulates both the frequency and the force of uterine contractions with cervical dilation, at a rhythm similar to natural labor, highly dependent on estrogen level and condition of uterus (receptor amounts, PLC-IP3-Ca 2+ pathway). (2) Breast: milk ejection. (3) Blood vessel: vasodilation at large dose. Uterine stimulants

6. 2. Clinical uses: - to expedite delivery and induced labor (2-5 U); administered by continuous iv infusion (short half-life time ~ 5 min) - to reduce the incidence and severity of postpartum hemorrhage ( 产后大出血, 5-10 U). Uterine stimulants Oxytocin (OXT, 催产素 )

7. 3. Adverse effects: - Intrauterine asphyxia ( 宫内窘迫 ) or uterine rupture (overdose) - Allergy - Water retention (ADH-like effect) 4. Contraindications: -- hypertonic dysfunction of uterus -- abnormality in birth canal -- abnormal fetal position Uterine stimulants Oxytocin (OXT, 催产素 )

8. Ergot alkaloids( 麦角生物碱 ) Ergometrine ( 麦角新碱 ) Ergotamine ( 麦角胺 ) Ergotoxine ( 麦角毒 ) Uterine stimulants

9. Ergot alkaloids( 麦角生物碱 ) 1. Pharmacological effects: (1) Uterus (ergometrine): -- strongly stimulates uterine smooth muscle, both the body and the cervix; ready to induce tonic contraction at larger doses, dependent on condition of uterus. (2) Blood vessel (ergotamine): -- contract peripheral blood vessels and cerebral vessels. (3) Block  receptor (ergotoxine, ergometrine) Uterine stimulants

10. 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. Uterine stimulants Ergot alkaloids( 麦角生物碱 )

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

12. 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: stimulate uterine smooth muscle. 2. Clinical uses: to induce labor 2. Adverse effects: GI reaction, attack of asthma (PGF 2  ); glaucoma (PGE2). Uterine stimulants

13. Objectives To observe the excitatory effect of oxytocin on uterine smooth muscles and the dose-effect relationship.

14. Methods 1.Estrodiol pretreatment (0.2mg) of rats (200 g  40g) 24hr before experiment; 2.Prepare the uterus smooth muscle specimen.

15. Methods The uterus of the rat

16. Methods The uterus of the rat

17. Methods Perfusion system

18. 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

19. 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 0.02 ml, 0.04 ml, 0.14 ml oxytocin (0.01U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly.

20. Methods 3.Add 0.04 ml, 0.14 ml oxytocin (0.1U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly. 4.Add 0.04 ml, 0.14 ml oxytocin (1U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly.

21. Methods 5.Add 0.04 ml, 0.14 ml oxytocin (10U/ml) into the perfusion system. Record the maximal force and frequency (optional) of contraction at each drug concentration accordingly.

22. 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.

23. 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。

24. Learning issues 1 ．缩宫素对子宫的作用及临床应用。 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？