Topic 30 - Local factors of cardiovascular regulation

Question 1

Words to include

Answer 1

• Perfusion (blood flow)
• Oxygen demand
• Nutrient demand
• Tissues
• Collapse of normal circulation
• Inproportional blood supply
• Local regulatory mechanisms
• Paracrine signals
• Central regulation
• Local regulation
• Short run
• Long run
• Intrinsic (local) short term regulation
  
  • Autoregulation by myogenic tone
    
    • Microcirculation
      
      • Peripheral blood pressure
    • Bayliss effect
      
      • Metarterioles
      • Pressure change
      • Perfusion (ml /min)
      • Blood pressure (mmHg)
      • Metabolic demand
      • Ischemia
      • Normal perfusion
      • Hyeremia
      • Metarteriole sphincter
        
        • Constriction
        • Relaxation
  • Endothelial related regulation
    
    • Endothelial cells
    • Humoral signals
    • Smooth muscles (in vessel wall)
    • Endothelium derived relaxing factor (EDRF)
      
      • Nitrogen monoxide (NO)
        
        • cGMP
      • Prostacyclin
        
        • cAMP
      • Endothelial-factor unrelated to NO and prostacyclins
    • Endothelium derived contracting factor
      
      • Endothelins (ET 1-4)
      • Cyclooxygenase dependent factor
        
        • TXA₂
        • NO degradation
      • Angiotensins-II
        
        • Vasoconstrictor
        • Endothelins
        • Sympathetic vasoconstriction
  • Acetylcholine
    
    • Nerve endings
      
      • Vasoconstriction
    • Lumen of blood vessel
      
      • Endothelium
      • Vasodilation
  • Regulation through metabolites
    
    • O₂-consumption (↑)
    • Adenosine concentration (↑)
    • H⁺ concentration (↑)
    • CO₂ concentration (↑)
    • K⁺ concentration (↑)
    • EDRF stimulation
    • NO production (↑)
    • cGMP (↑)
    • Hypoxia
• Intrinsic (local) long term regulation
  
  • Growth factors
  • Enzyme induction
  • Angiotensins
  • Hyperemia
    
    • Active hyperemia
    • Reactive hyperemia
      
      • Secondary increase

Question 2

Intrinsic (local) regulation

General

Answer 2

• Either:
  
  • Short term
  • Long term
• Regulated by fast, local, auto-regulative processes

Question 3

What is intensity of perfusion (blood flow) determined by?

Answer 3

Oxygen and nutrient demand of the organ

Question 4

Intrinsic (local) short term regulation

Local factors

Answer 4

• Tissues adjust their own perfusion by local factors:
  
  1. Autoregulation by myogenic tone
  2. Endothelial related regulation
  3. Acetylcholine
  4. Regulation through metabolism

Question 5

Intrinsic (local) short term regulation

Local factors: autoregulation by myogenic tone

Answer 5

• Microcirculation should not be influenced by the changes of peripheral blood pressure
• Bayliss effect
  
  • Pressure changes initiate adequate response of metarterioles sphincters
  • Perfusion will adapt to the metabolic demand

Question 6

Intrinsic (local) short term regulation

Local factors: endothelial related regulation

Answer 6

• Blood pressure mechanically deforms endothelial cells
  
  • ​Promotes the endothelial cells to produce humoral signals that influences the contraction state of smooth muscles in the wall of the vessels
• Two major classes of such factors:
  
  1. Endothelium Derived Relaxing Factor (EDRF)
     
     • Nitrogen monoxide
       
       • ​Penetration to smooth muscle, cGMP ↑ = smooth muscle relaxation
     • Prostacyclin
       
       • ​NO production ↑
       • Direct muscle relaxation effect, by cAMP ↑
     • Endothelial-factor
       
       • Hyperpolarization by activating ATP dependent K-channels
         
         • ​K⁺is anindirect vasodilator
  2. Endothelium Derived Contracting Factor (EDCF)
     
     • ​​Endothelins (constrictor)​
     • Cyclooxygenase dependent factor
       
       • ​TXA₂
       • Stimulates NO degradation
     • Angiotensins-II
       
       • ​Direct vasoconstrictor
       • Stimulates production of endothelins
       • Sympathetic vasoconstriction ↑

Question 7

Intrinsic (local) short term regulation

Local factors: acetylcholine

Answer 7

• Role:
  
  1. Through nerve endings
     
     • ​Delibiration of ACh by direct stimulation of the vessel
     • Vasoconstriction
  2. Arriving from the lumen of blood vessel
     
     • ​Will act through endothelium
     • NO production ↑
     • Vasodilation

Question 8

Intrinsic (local) short term regulation

Local factors: regulation through metabolites

Answer 8

• Most important local autoregulative element
• Mechanism of action:
  
  • ↑ metabolic activity:​
    
    • ↑ O₂-consumption
    • ↑ adenosine concentration
    • ↑ H⁺ concentration
    • ↑ CO₂ concentration
    • ↑ K⁺ concentration
• All of these factors stimulate endothelium (EDRF stimulation)
• Response:
  
  • NO production ↑
  • Diffusion of NO into the smooth muscles
  • cGMP ↑ = relaxation
• Lack of oxygen at tissue level (hypoxia) causes an automatic increase of the perfusion, resulting in better O₂ supply

Question 9

Intrinsic (local) long term regulation

Answer 9

• Intensive and sustained work of an organ causes morphological changes that contribute to the better perfusion at the local level
• Growth factors, enzyme induction etc.
• Increased perfusion via angiogenesis (rearrangement and formation on new vessels)

Hyperemia:

• Hyperemia: ↑ local perfusion

1. Active hyperemia
   
   • Functional
   • If hyperemia is related to increased metabolic activity of the tissue
2. Reactive hyperemia
   
   • Secondary increase of perfusion
   • I.e. compression of the artery of the limb reduces perfusion (pale), hyperemia happens, however, after compression is released