Cilazapril delays progression of hypertension and uremia in rat polycystic kidney disease.
Polycystic kidney disease (PKD) is the fourth most common cause of end-stage renal disease and is a common cause of hypertension and associated vascular morbidity. Activity of the renin angiotensin system has been identified as a major component of hypertension and altered fluid and electrolyte physiology in PKD. Activity of this pathway also has been proposed as a potential modulator of structural change in both tubules and the interstitium of the kidney. Cilazapril is a long-acting angiotensin-converting enzyme inhibitor that has been effective in producing vascular remodelling in hypertensive vascular disease. We undertook a study to determine whether therapy with cilazapril would modify the expression of PKD in the Han:SPRD-cy rat, a model of autosomal dominant PKD that closely resembles human disease. Male rats were treated for 4 months, starting at 1 month of age. Control animals were hypertensive by 3 months of age, whereas treated animals were noted to be hypertensive only at the exit assessment (P < 0.001 at 3 months, P = 0.005 at 5 months). At 5 months of age, cilazapril-treated animals had modest but statistically significant reductions in serum creatinine (mean, 1.77 mg/dL v 1.97 mg/dL; P = 0.0006) and morphometrically assessed cyst volume (mean, 0.32 mL v 0.67 mL; P = 0.036). Cilazapril is an effective treatment for hypertension in this model of progressive renal disease and may have benefits beyond the prevention of cardiovascular morbidity.
Ogborn
M R
MR
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
Sareen
S
S
Pinette
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017315:Cilazapril / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology*; D008297:Male; D007690:Polycystic Kidney Diseases / Q000150:complications*; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000209:etiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017315:Cilazapril; D003404:Creatinine