Effect of sodium chloride, enalapril, and losartan on the development of polycystic kidney disease in Han:SPRD rats.
We found that the administration of an angiotensin I-converting enzyme inhibitor and sodium chloride loading lessen the development of renal cystic disease induced by 2-amino-4-5-diphenylthiazole in rats. To determine whether similar effects could be observed in an autosomal dominant model of polycystic kidney disease, heterozygous cystic (Cy/+) and homozygous normal (+/+) Han:SPRD rats were divided into experimental groups at 3 weeks of age. The first study included four groups receiving enalapril (50 mg/L), losartan (400 mg/L), hydralazine (80 mg/L), or no drug in their drinking water. The second study included four groups fed a sodium-deficient diet or the same diet supplemented with 0.25%, 0.6%, or 3.3% sodium chloride. The Cy/+ rats receiving enalapril had lower kidney weights and histologic scores than those in the control group, and lower kidney weights, plasma creatinines, and histologic scores than those in the hydralazine group. The Cy/+ rats receiving losartan had lower plasma creatinines and histologic scores than those in the control and hydralazine treatment groups. A sodium-deficient diet markedly blunted the growth of the animals and the development of cystic disease. Increases in the sodium content of the diet in the other three groups were accompanied by higher relative kidney weights and histology scores, while the levels of plasma creatinine were not significantly different. Regression of the cystic disease was observed between 3 and 4 months of age. These results indicate that the development of autosomal dominant polycystic kidney disease in the rat can be modulated by pharmacologic and nutritional factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Keith
D S
DS
Department of Pediatrics, Mayo Clinic, Rochester, MN 55905.
Torres
V E
VE
Johnson
C M
CM
Holley
K E
KE
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D019808:Losartan; D008297:Male; D007690:Polycystic Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology* / Q000627:therapeutic use; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D012965:Sodium Chloride; D004656:Enalapril; D003404:Creatinine; D012083:Renin; D019808:Losartan