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Uterine Contractility. Dinaz Lahewala Fall 2011. Outline. Purpose Background Information In-class experiment Questions & Answers. Purpose. Continue discussing properties of Smooth Muscle (esp. of the uterus) Determine the oxytocin dose response in three treatment groups of rats

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uterine contractility

Uterine Contractility

DinazLahewala

Fall 2011

outline
Outline

Purpose

Background Information

In-class experiment

Questions & Answers

purpose
Purpose
  • Continue discussing properties of Smooth Muscle (esp. of the uterus)
  • Determine the oxytocin dose response in three treatment groups of rats
  • Determine the effect drugs on smooth muscle
  • Determination of female mammalian reproduction cycles
    • 4 different stages
the uterus
The Uterus
  • What is it?
    • Reproductive sex organ
      • Sexual Response
        • Direct blood flow to various parts including ovaries
          • Transfer of hormones
      • Reproductive function
        • Accept fertilized egg from fallopian tube
        • Expands during pregnancy

What are the differences between a human uterus and rat uterus?

the uterus1
The Uterus
  • Non-striated smooth muscle
  • Under autonomic control
    • Sympathetic stimulation
      • Decrease in rhythmic contractility
      • Vasoconstriction
    • Parasympathetic
      • Increase in contractility
      • Little effect on arterial smooth muscle*
different treatments of rats
Different Treatments of Rats
  • Control Group
  • Ovariectomized Rat
  • Ovariectomized Rat with estrogen injections
  • What changes between these three treatment groups?
    • How does this relate to the uterus?
control rats
Control Rats
  • Normal Uterus (~estrus)
ovariectomized rat
Ovariectomized Rat
  • Removal of Ovaries
ovariectomized rat with estrogen
Ovariectomized Rat with Estrogen
  • Removal of Ovaries with estrogen injections
slide11
Why?
  • Estrogen
    • Sex steroidal hormone acts as a growth hormone for tissue for reproductive organs
      • Induces ovulation
    • Increases myometrial sensitivity to oxytocin
  • Progesterone
    • Another sex steroid hormone
    • Counter-effects estrogen
    • Released by corpus luteum
    • Pregnancy hormone
    • Decreases sensitivity to oxytocin
preparation
Preparation
  • 1 cm of uterine horn
preparation1
Preparation
  • Vaginal Smear to determine stage of estrous cycle
    • Place a small cotton swab into the rats vagina, and placed sample on slide
    • Assessed cell types found to determine which stage of the estrus cycle the rat was in.
estrous vs menses
Estrous Vs. Menses
  • Estrous Cycle in placental mammals/ Menses (Menstrual) cycle in humans
    • 5 day cycle (compared to 28 days)

-only receptive to sex during "heat“ - estrus-ovulation linked to mating in some species (neuroendocrine reflex results in LH surge)-no sloughing of uterine lining (endometrium)

estrus cycle
Estrus Cycle
  • Proestrus
    • Increasing levels of FSH and LH
      • Stimulates follicular growth and secretion of estrogens
      • Vaginal smears contain mainly nucleated epithelial cells
      • Lasts 8 to 12 hrs
  • Estrus
    • Period of “heat” and copulation
    • High levels of estrogen
    • Vaginal smears contain many cornified cells and a few leukocytes or nucleated cells
    • Lasts 9 to 15 hrs
estrus cycle1
Estrus Cycle
  • Metestrus
    • LH and LTH promote formation of corpus luteum
    • Increased levels of progesterone and estrogens
    • Vaginal smears contain many leukocytes and some cornified cells
    • Lasts 10 to 14 hours
  • Diestrus
    • Longest stage lasting 60-70 hours
    • Corpus luteum regresses and uterus is smaller
    • Lowest levels of sexual hormones
    • Vaginal smears contain mostly leukocytes
questions
Questions!
  • What stage of the estrus cycle do you think the ovariectomized rat would be in?
    • Diestrus Cycle
  • How about the ovariectomized rats receiving estrogen replacement injections?
    • Estrus Cycle
  • What is the role of the estrogen during the estrus cycle?
    • Stimulate mitosis of cells in the uterus and vagina
oxytocin
Oxytocin
  • Sex hormone released by posterior pituitary (controlled by hypothalamus)
  • Has role in orgasms, social recognition, bonding, trust, and maternal behaviors
  • Receptor is a G-protein receptor
    • IP3 formation  Ca+2 release of SR into cell  contraction of smooth muscle
oxytocin1
Oxytocin
  • Uterine contractions
    • To expel endometrial blood
    • During labor
    • After labor: clotting/expulsion of placenta
  • Lactation/Brest Feeding
    • Acts on mammary glands to cause milk “let down”
      • Suckling effect triggers hypothalamus to produce oxytocin to be released by the pituitary gland
question
Question!

What role does oxytocin play in:

a) Parturition

b) Breast feeding?

slide22
ED50

Response (units)

Concentration (units)

Amount of dosage needed in order to produce 50% of the maximum stimulus

results effects of various treatments
Results - Effects of Various Treatments
  • Oxytocin produced a greater response in those with estrogen when compared to those not with estrogen
    • Estrogen promotes up regulation of oxytocin receptors
      • Uterus more sensitive
      • 85% increase in tone for control
      • ~75% increase in tone for ovariectomized with estrogen
      • 70% increase in tone for ovariectomized with no injection
      • (Remember this is data, and not the expected!!!)
slide25
Acetylcholine

In Peripheral Nervous System

  • Activates muscles and when binds to Ach receptors it opens ligand gated sodium channels in the cell membrane. Sodium ions then enter the muscle cell, stimulating muscle contraction

In Central Nervous System

  • Has a variety of effects as a neuro modulator upon plasticity, arousal and reward. ACh has an important role in the enhancement of sensory perceptions when we wake up and in sustaining attention
  • Increases contractility in smooth muscle
slide27
Epinephrine

Increases heart rate, contracts blood vessels and dilates air passages and participates in the "fight or flight" response of the sympathetic nervous system.

Decreases contractility in uterine smooth muscle

propanolol
Propanolol

Non selective beta blocker

Competes with adrenergic epinephrine receptors

No significant changes

questions1
Questions

4) Do oxytocin and acetylcholine exert their effects via different receptors?

5) How does propranolol alter the effects of epinephrine on uterine contractility?

slide31
4) Yes

5) Supposed to compete with epinephrine

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