Effect of clonidine on the progression of chronic renal disease in partially nephrectomized rats.
The effect of clonidine, on alpha 2-agonist and antihypertensive, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Treatments began four weeks after the removal of approximately 70% of renal mass. Clonidine was given once daily by gavage on an increasing dose schedule of 50 micrograms/kg for 4 weeks, followed by 100 micrograms/kg for 8 weeks and finally 200 micrograms/kg for 6 weeks. Measurements of renal functions were made at 4 week-intervals during treatment. After 18 weeks, clonidine-treated rats had lower levels of plasma urea nitrogen (P less than 0.05) and plasma creatinine (P less than 0.05). Urinary protein excretion rates were lower in clonidine-treated rats while receiving 100 micrograms/kg at 8 weeks (P less than 0.05) and 200 micrograms/kg at 18 weeks (P less than 0.05). At the end of the treatment period, anesthetized clonidine-treated rats had a numerically lower mean arterial pressure (p = 0.08), but no difference in the histological ranking of light microscopic lesions (P greater than 0.10). Based on the functional data, we conclude that clonidine retards the deterioration of renal function in this model of chronic renal disease. The lack of a consistent effect of clonidine on proteinuria and no reduction in the severity of morphological damage indicates that clonidine is less effective than previously reported treatment in this model with angiotensin converting enzyme inhibition. These differences in efficacy may be related to differences in intraglomerular hemodynamic alterations and could be an important consideration in the selection of therapies for individuals with hypertension and renal insufficiency.
Wilke
W L
WL
Department of Physiology, Colorado State University, Fort Collins 80523.
Fettman
M J
MJ
Tan
A A
AA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004656:Enalapril / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains
D004656:Enalapril; D003404:Creatinine; D003000:Clonidine