Increased arterial stiffness and aortic calcification
are common for hypertension and kidney disease
Background1
• In both humans and the rat, stiff conduit arteries are less able to
buffer pulsatile changes in blood pressure, provoking CV and renal
outcomes1.
• Arterial calcification is associated with hypertension and arterial
stiffening2.
• Arterial calcification and increase in arterials stiffness is also a
hallmark of chronic kidney disease (CKD).3
1. Keith Ng , Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966. 2.London GM, Marchais SJ, Guerin AP. Arterial stiffness and function in endstage renal disease. Adv Chronic Kidney Dis. 2004;11(2):202-209. 3. Temmar M, Liabeuf S, Renard C, et al. Pulse wave velocity and vascular calcification at
different stages of chronic kidney disease. J Hypertens. 2010;28(1):163-169.
Impact of ACE inhibition on arterial structure and
function in a model of cystic renal disease
Methods
Study groups:
• Untreated Lewis polycystic kidney (LPK), LPK treated with perindopril
(3 mg/kg/day p/o in the drinking water) from age 6-12 weeks and
normotensive Lewis controls.
• LPK
rats develop an early hypertension and marked aortic
calcification.
Measurements:
• Arterial stiffness was measured as aortic pulse wave velocity (PWV)
• Systolic pressures (SBP)
• Tissue histomorphology from aortic segments
• Calcium content (by atomic absorption spectroscopy)
• Wall elastic modulus (EM) and wall stress (WS)
1. Keith Ng , Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966.
Significant reduced aortic calcification in treated
with perindopril LPK rats
P<0.05
1. Keith Ng, Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966.
Perindopril improves elastin density (A,B)…
…and reduces pathological collagen deposit (C,D)
1. Keith Ng, Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966.
Significant reduction in blood pressure and
improvement in aortic elasticity indices
Treatment with perindopril limits an age-related increase in blood pressure and
reduction in aortic elasticity, which naturally occurs in polycystic rats (LPK)
between 6 and 12 weeks of age.
1. Keith Ng, Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966.
Treatment with perindopril limits progressive aortic
stiffening in polycystic kidney model
ACE inhibition with perindopril brought the 12-wk-old LPK curves back to
the same level as 12-wk-old normotensive Lewis control animals
1. Keith Ng, Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966.
ACE inhibition with perindopril improved the
structural and functional indices of aortic stiffness
Conclusions
• Compared to normotensive Lewis controls, polycystic kidney (LKP) rats
become hypertensive, have marked aortic calcification and remodeling.
• This is the first study to show that sustained treatment with perindopril
can produce a marked inhibition of the progression of hypertension,
calcification and associated arterial stiffness in a naturally occurring
rodent model of CKD.
• Further investigation of the renin-angiotensin system and its inhibition
may open up improved treatment pathways for complex disease
conditions that are associated with the development of arterial
calcification and increased arterial stiffness.
1. Keith Ng, Hildreth CM, Avolio AP, Phillips JK. Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of
cystic renal disease. Am J Physiol Renal Physiol. 2011;301(5):F959-F966.
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