Renal function and structure in a rat model of arterial calcification and increased pulse pressure.
Clinical studies suggest a strong link between tissue calcification and pressure hyperpulsatility in end stage renal disease patients. Using a Wistar rat model of arterial elastocalcinosis and hyperpulsatility [vitamin D and nicotine (VDN) treatment], we evaluated the relative importance of tissue calcification and hyperpulsatility in the etiology of renal failure. VDN rats showed significant increases in aortic wall calcium content (50 times; 992+/-171 vs. control 19+/-1 micromol/g dry wt) and pulse pressure (1.5 times; 61+/-4 vs. control 40+/-2 mmHg). Significant renal calcification (16 times; 124+/-27 vs. control 8.1+/-0.7 micromol/g dry wt) occurred mainly within the media of the preglomerular vasculature and in the areas of interstitial fibrosis in VDN. Extensive renal damages (5 times; 26+/-5% of collapsed-atrophic or sclerotic glomeruli, or glomerular cysts vs. control 5.2+/-0.3%; 28 times; 61+/-12% areas of focal, cortical areas exhibiting interstitial fibrosis per section vs. control 2.2+/-0.6%) were observed histologically. The glomerular filtration rate significantly decreased (880+/-40 vs. control 1,058+/-44 microl.min(-1).g kidney wt(-1)). Albuminuria increased six times (1.6+/-0.4 vs. control 0.27+/-0.04 mg/24 h). There were significant linear relationships between albuminuria and pulse pressure (r2=0.408; n=24) or renal calcium content (r2=0.328; n=24; P<0.05) and between glomerular filtration rate and pulse pressure (r2=0.168; n=27). To our knowledge, this study provides the first evidence of links between both 1) hyperpulsatility and renal dysfunction, and 2) renal calcification and renal dysfunction. Given the increasing frequency of end-stage renal disease, this model could prove useful for preclinical evaluation of drugs that prevent or attenuate hyperpulsatility and/or tissue calcification.
Gaillard
Virginie
V
Cardiovascular Pharmacology Laboratory, Pharmacy Faculty, Nancy University, 5 rue Albert Lebrun, 54 000 Nancy, France.
Jover
Bernard
B
Casellas
Daniel
D
Cordaillat
Magali
M
Atkinson
Jeffrey
J
Lartaud
Isabelle
I
D000419:Albuminuria / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D021461:Animals, Outbred Strains; D001011:Aorta / Q000473:pathology*; D001284:Atrophy; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight; D002114:Calcinosis / Q000473:pathology* / Q000503:physiopathology*; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D005355:Fibrosis; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002118:Calcium