Lecture 7: Experimental Hypertension Flashcards
Why do we use animal models?
Greater experimental possibilities
Shorter time frames
Better standardisation and control
Relatively cheap
What hypertensive models are there?
Surgery or drugs
Breeding
What are the 3 phases of hypertension?
Development phase - moving out of normal BP to high BP, BP stimuli active
Established phase - adaptive responses
Malignant phase - don’t see as much, failure
How does BP stimuli influence the kidneys?
Renin release
Increase in angiotensin = increase in TPR
Reduced GFR
Na and water retention
Increased contribution to TPR
Efferent renal nerve stimulation
- nerves to kidneys: renin, vasocontriction, increase BP
- nerves back from kidneys to spinal cord: increase BP by picking up signals from kidneys
If BP increases some pressure gets transmitted to the kidney. Central BP increase causes?
Kidney to excrete Na as a safety mechanism
If BP stays elevated for long period of time the kidney adjusts so it doesn’t excrete as much Na
What adaptive responses occur?
Cardiac hypertrophy
Vascular hypertrophy
Altered renal pressure-natriuresis relationship - sodium excretion through the kidney, adaptive response can be problematic
What is surgically-induced hypertension?
Designed to replicate renovascular hypertension
Mostly renal models
- restricting blood supply to kidneys
- reducing functional renal tissue
What types of renal ischaemia models are there?
Affecting all renal tissue: - 1 kidney, 1 clip (1K1C) - 2 kidneys, 2 clips (2K2C) Affecting some renal tissue - 2 kidneys, 1 clip (2K1C)
What types of reduced renal tissue models are there?
1 and 2/3 nephrectomy - remove 1 and 2/3 of kidneys
Renal wrap - wrap kidney in cellophane inflammatory repsonse
What drug induced models are there?
Long term infusions of: Angiotensin Renin NOS blockade Endothelin (vasoconstrictor) Noradrenaline Mineralocorticoid (DOCA) and high salt - retain Na
What does 1K1C and 2K2C models affecting all renal tissue cause?
Brief early rise in renin
Predominant ECF expansion
Later hypertrophy of vessels and increased TPR
Ability to secrete Na is poor
What does 2K1C model affecting some renal tissue cause?
Predominant renin release early
Unclipped kidney makes up for lost function of clipped kidney - acts as a pressure release valve
Hypertension eventually damages unclipped kidney - relationship natriuresis occurs
Predominant ECF expansion later on
What is the DOCA salt model?
Uninephrectomy and DOCA injections
Salt and water retention
Renin suppression
DOCA is a mineralocorticoid, it shows a change in the pressure natriuresis relationship & has a higher BP if one kidney is removed
What are the two types of doses of angiotensin infusions?
Pressor doses:
- direct vasoconstrictor effect
- angiotensin, BP increases straight away
Sub-pressor doses:
- direct trophic effect
- causes vessel growth to increase resistance and put up TPR
What makes you susceptible to BP stimuli?
Being younger
Possibly related to the hormonal milieu of growth
