Effects of chronic felodipine treatment on renal function and morphology in SHR.
To investigate if blood pressure reduction per se may prevent progressive renal disease in aging spontaneously hypertensive rats (SHR), 15-month-old SHR were treated with the calcium antagonist felodipine, with the beta-blocker metoprolol or with the combination for six months. The combined regimen caused the greatest blood pressure reduction over time, metoprolol caused the least, while felodipine had an intermediate effect. At the end of treatment, urinary protein excretion and endogenous creatinine clearance were determined in rats kept in individual metabolic cages. At autopsy, the kidneys were histologically examined and indices of chronic progressive nephrosis and glomerular sclerosis were determined. A positive correlation was found between urinary protein excretion and glomerular sclerosis. Glomerular sclerosis was low in the groups of rats with high endogenous creatinine clearance. In both groups treated with felodipine, glomerular sclerosis and urinary protein excretion were significantly reduced compared to untreated controls. These results illustrate that the calcium antagonist felodipine attenuates proteinuria and glomerular sclerosis in aging SHR. The blood pressure reduction may be of major importance in this respect, although a direct action on the sclerotic process within the glomeruli may also contribute.
Nordlander
M
M
Department of Pharmacology, Astra Hässle Research Laboratories, Mölndal, Sweden.
Havu
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D004357:Drug Synergism; D015736:Felodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008790:Metoprolol / Q000008:administration & dosage / Q000627:therapeutic use; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011918:Rats, Inbred SHR; D014882:Water-Electrolyte Balance / Q000187:drug effects
D003404:Creatinine; D008790:Metoprolol; D015736:Felodipine