A L3.1 Experimental hypertension

Question 1

Why are animal models used?

Answer 1

• Offer greater experimental possibility
• Shorter time frames
• Standardise & Control
• Relatively cheap

Question 2

Phases of hypertension (occurs regardless of cause)

Answer 2

• Development
  
  • Normal pressure → stimuli causing it to ↑
• Established
  
  • Once reached high levels, stops, copes via adaptive responses
• Malignant
  
  • Exposed to BP not going back to normal
  • Adaptive response no longer coping → further ↑BP

Question 3

Developmental phase

Answer 3

• BP stimuli mostly from kidneys
  
  • Renin release
  • ↓GFR
  • NA/H2O retention
  • ↑TPR
  • Efferent renal N stimulation

Question 4

Established phase

Answer 4

• Adaptive responses:
  
  • Cardiac hypertrophy
  • Vascular hypertrophy - vessels stretch but want to retain size (S.M worked)→ ∴ S.M hypertrophy → thicker walls
  • Altered renal pressure - natriuresis relationship (kidney regulation via ↑Na excretion as a response to ↑BP)

Question 5

Why are adaptive responses sometimes prostulated as stimuli?

Answer 5

• Cardiac hypertrophy → ↑SV
• Vascular hypertrophy → ↑constriction → ↑TPR
• Kidney changes function → Na retained → ↑BP → then nutriuresis relationship kicks in & ↑Na excretion

Question 6

Surgically inducing hypertension: by restricting BS to kidneys

Answer 6

• Restricts BS to kidneys → clip ~ renal A (1K1C, 2K2C)
• Brief early rise in renin
• Pre-dominant ECF expansion
• Later hypertrophy of vessels & ↑TPR

Question 7

Surgically inducing hypertension: by reducing function of renal tissue

Answer 7

• causing kidney failure (2K1C)
• 1 kidney functioning properly (excreting Na)
• The other clipped & retains Na (receiving ↓BS → signal for low BP) → ↑BP from Na retention → kidney failure
• Could also wrap kidney in cellophane

Question 8

Drugs inducing hypertension

Answer 8

• ANG
  
  • Pressor doses - direct vasoconstriction → ↑TPR
  • Sub-pressor doses - direct trophic effect (growth of vessel walls)
• Renin
• NOS blockade
  
  • NO is a vasodilator
• Endothelin
  
  • Potent potent vasoconstrictor
• Mineralocorticoid
  
  • DOCA
  • Na/H2O retention
  • Renin suppressed throughout

Question 9

Are young or old subjects more susceptible to BP stimuli

Answer 9

• Young subjects are more susceptible than old to BP stimuli
  
  • May be a result of hormonal changes

Question 10

Malignant phase of hypertension

Answer 10

• Persistent ↑ in BP
• Vessel damage (esp. preglomerular arterioles) → ∴unable to regulate BP
• ↑renin, ↓GFR
  
  • Damage to vessels so severe → block off
  • Downstream, preglomerular arterioles detect a lowered pressure → release renin
• Rapid rise in BP & diuresis
  
  • Remaining glomerular cells under stress
    
    • Leads to hyperfilter → overcomes tubules ability to reabs Na/H2O → weight loss/illness/death

Question 11

Why are genetic models used

Answer 11

• prove genes affect BP
• Identification of genes affecting BP
• Understand genetic mechanisms

Question 12

What are young SHR?

Answer 12

• Selected for high BP
• ↑Sympathetic N
  
  • ↑renin
  • ↑GFR
  • ↑Na retention

Question 13

Effect of an ACE inhibitor during youth

Answer 13

• Perindopsil - an ACE inhibitor
• Targets RAS during youth
• When given to SHR during 6-10wks → BP never returns to pre-disposed levels of young SHR
  
  • Shows genetic stimuli may only be in youth

Question 14

Dalh rats

Answer 14

• Selected for high BP after exposed to high salt diet
• By working backwards → linking phenotype & genes in offspring that continue to inherit high BP → able to find genes for BP
• Found: gene mutation on chrm 7 → affects 19-OH-DOC substrate recognition site (have ↑lvls)
  
  • Is usually suppressed by high salt diet → but not suppressed in dalh rat’s mutation