L6.1 Hormonal control of cardiac function

Question 1

Features of adrenaline

Answer 1

• SNS hormone → stimulates heart functions
• Secreted from adrenal medulla (modified sympathetic ganglion)
  
  • Release A into blood stream (No post ganglion neurons)

Question 2

Overview of the SNS receptors

Answer 2

Question 3

Inotropic and chronotropic

Answer 3

• Inotropic = affects contractility
• Chronotropic = Affects HR

Question 4

How do b1 cardiomyocytes increase contractility

Answer 4

• Increase L&T type Ca current
• Increase SR Ca release channels
• Increase Ca transient via PKA
• Increase Ca ATPase (SERCA)

Question 5

Mechanism of b1

Answer 5

• Acts via Gas → adenyl cyclase → cAMP → PKA → phosphorylates proteins → regulation
  
  • Increase Ca transients → more rapid relaxation

Question 6

Mechanism of a1

Answer 6

• (Increase Ca sensitivity)
• Gq protein → splits subunits → PLC (uses membrane as signaling process)
  
  • PLC catalyses: PIP2 → DAG + IP3 (For nuclear transcription/SA node function)
  • DAG → PKC activation → increase pH → increase myofilament Ca sensitvity

Question 7

What is the effect of pH

Answer 7

• Alkaline pH shifts induces forces increase
• Ca & pH effects are additive

Question 8

a vs b inotropic effects

Answer 8

• b > a Ca transient
  
  • Ca transient occurs before twitch
• b1 stimulates increase force by 20% & Ca transient by 400%
• a has greater contraction value for less Ca load
• BUT b contractions is faster than a
  
  • Increase time to ventricle to relax → Increase time for ventricle to fill → Increase SV in next pump

Question 9

Vasoconstrictor inotropic agents: Endothelin-1

Answer 9

• Inotropic
• But when systematically → Decrease O2 supply to heart → Decrease contractility
• Produced from:
  
  • Endocardial & Endothelial cells
  • Fibroblasts

Question 10

Vasoconstrictor inotropic agents: ANGII

Answer 10

• PKC >> PKA → Increase sensitivity (Na/H) & Ca entry (Ca channels)
• Systemically infused → vasoconstrictor → Decrease O2 supply to heart and hence decrease contractility
• BUT enhances contractility when applied to isolated heart muscles
• Produced from:
  
  • Endocardial & endothelial cells
  • Fibroblasts + CARDIOMYOCYTES

Question 11

Local or distal actions of ET1 & ANGII?

Answer 11

• Both endothelin and ANG II are primary LOCAL mediators (spillovers into circulation → SE)

Question 12

Intracardiac functional role of ANGII

Answer 12

• Too much ANG II → earlier mortality
• Acute ANG II → Increase pump functions
• Chronic ANG II → Decrease pump function (due to hypertrophy leading to decompensation)

Question 13

When are ET-1 and ANGII produced/

Answer 13

Produced and released in heart in response to stretch and growth factors

Question 14

ANF

Answer 14

• -ve inotropic
• Synthetised & released by atrial myocyte (responds to stretch)
• Relief strain on heart muscles (cardiomyocyte relaxation)
• Binds & activates guanylyl cyclase activity (Converts GTP to cGMP → activating PKG)
• Promotes H2O & Na excreted → Decrease BV (renal vasodilation)
• Induces relaxation → Decreases Ca current & Increase SR Ca ATPase