title: Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of cystic renal disease.
abstract: The effect of angiotensin-converting enzyme inhibition on function and structure of the aorta was studied in the Lewis polycystic kidney (LPK) rat model of cystic renal disease and Lewis controls. Pulse-wave velocity (PWV) was recorded under urethane anesthesia (1.3 g/kg ip) in mixed-sex animals aged 6 and 12 wk and in 12-wk-old animals treated with perindopril (3 mg·kg(-1)·day(-1) po) from age 6-12 wk. Tail-cuff systolic pressures were recorded over the treatment period. After PWV measurements, animals were euthanized and the aorta was removed for histomorphological and calcium analysis. Hypertension in LPK at 6 and 12 wk was associated with a shift of the PWV curve upward and to the right, indicating a decrease in aortic compliance, which was significantly reduced by perindopril. LPK demonstrated greater aortic calcification (6 wk: 123 ± 19 vs. 65 ± 7 and 12 wk: 406 ± 6 vs. 67 ± 6 μmol/g, P < 0.001, LPK vs. Lewis, respectively). This was reduced by treatment with perindopril (172 ± 48 μmol/g, 12 wk LPK P < 0.001). Medial cross-sectional area and elastic modulus/wall stress of the aorta were greater in LPK vs. Lewis control animals at 6 and 12 wk of age and showed an age-related increase that was prevented by treatment with perindopril (P < 0.001). Perindopril also ameliorated the degradation of elastin, increase in collagen content, and medial elastocalcinosis seen in 12-wk LPK. Overall, perindopril improved the structural and functional indices of aortic stiffness in the LPK rats, demonstrating a capacity for angiotensin-converting enzyme inhibition to limit vascular remodeling in chronic kidney disease.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Keith
authors.initials: K
authors.lastname: Ng
authors.forename: Cara M
authors.initials: CM
authors.lastname: Hildreth
authors.forename: Alberto P
authors.initials: AP
authors.lastname: Avolio
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Phillips
mesh_terms: D000375:Aging / Q000502:physiology; D019412:Anatomy, Cross-Sectional; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002114:Calcinosis / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003187:Compliance; D004548:Elasticity / Q000502:physiology; D005260:Female; D006977:Hypertension, Renal / Q000503:physiopathology; D052177:Kidney Diseases, Cystic / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D020913:Perindopril / Q000494:pharmacology*; D051381:Rats; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D002118:Calcium; D020913:Perindopril