Pravastatin modulates early diabetic nephropathy in an experimental model of diabetic renal disease.
BACKGROUND
Development of diabetes causes early functional (endothelial dysfunction) and morphological abnormalities in the kidney. If left untreated, these will ultimately progress to renal failure. Apart from strategies aimed at maintaining very tight glycemic control, attention has turned to the development of adjuvant therapy to maintain endothelial function in these patients. The agents receiving the most critical appraisal due to their endothelial protective effects are the 3-hydrox 3-methylglutaryl (HMG)-Co-enzyme A (CoA) reductase inhibitors. The aim of the study was to investigate: (1) the early alterations in the renal diabetic injury; and (2) to examine the protective role of Pravastatin in this end-organ diabetic model.


METHODS
Sprague Dawley rats (n = 21) were randomized into three groups: (1) control; (2) diabetic; and (3) diabetic treated with Pravastatin. Diabetic nephropathy was investigated with serum biochemical parameters (urea, creatinine), functional parameters (total urinary protein loss, glomerular filtration rate, renal cortical blood flow), and structural assessment (hemotoxylin and eosin staining).


RESULTS
We demonstrated impairment in functional, biochemical, and structural parameters in the diabetic nephropathy group, which was diminished by treatment with Pravastatin. This was attributed to an up-regulation in endothelial constitutive nitric oxide synthase (ecNOS) expression in the treated diabetic group.


CONCLUSIONS
We have shown that Pravastatin, in an experimental model of early diabetes nephropathy preserves microvascular endothelial function in the presence of hyperglycemia, thus inhibiting the early stage of diabetic microangiopathy.
Casey
R G
RG
Department of Surgical Research, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. rcasey@oceanfree.net
Joyce
M
M
Roche-Nagle
G
G
Chen
G
G
Bouchier-Hayes
D
D
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017035:Pravastatin / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D051437:Renal Insufficiency / Q000517:prevention & control*; D014280:Triglycerides / Q000097:blood; D014556:Urine
D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D017035:Pravastatin