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Excitatory effect of uterine stimulants on uterine smooth muscle
Shi-Hong Zhang （张世红）Dept of Pharmacology
Experimental pharmacology of reproductive system
• 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
Pituitrin(垂体后叶素 )
• oxytocin • vasopressin 血管加压素 (ADH)
Uterine stimulants
Oxytocin (OXT, 催产素 )
Uterine stimulants
Vincent du Vigneaud (1901-1978, USA)
Won Nobel prize in Chemistry in 1955 for isolation and synthesisof oxytocin
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-Ca2+ pathway).
(2) Breast: milk ejection.
(3) Blood vessel: vasodilation at large dose.
Uterine stimulants
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 )
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 )
Ergot alkaloids(麦角生物碱 )
Ergometrine (麦角新碱 )
Ergotamine (麦角胺 )
Ergotoxine (麦角毒 )
Uterine stimulants
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
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 )
3. Adverse effects: -- nausea, vomiting, BP ; -- allergic reaction;
-- prohibited in expediting delivery and induced labor.
Uterine stimulantsUterine stimulants
Ergot alkaloids(麦角生物碱 )
Prostaglandins (PGs, 前列腺素 )
Dinoprostone (地诺前列酮 , PGE2)
Dinoprost (地诺前列素 , PGF2)
1. Pharmacological effect: stimulate uterine smooth muscle.
2. Clinical uses: to induce labor
2. Adverse effects: GI reaction, attack of asthma
(PGF2); glaucoma (PGE2).
Uterine stimulants
Objectives
• To observe the excitatory effect of
oxytocin on uterine smooth muscles
and the dose-effect relationship.
Methods
1.Estrodiol pretreatment (0.2mg) of rats (200 g
40g) 24hr before experiment;
2.Prepare the uterus smooth muscle specimen.
Methods
The uterus of the rat
Methods
The uterus of the rat
Methods
Perfusion system
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
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.
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.
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.
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.
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。
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？
