Effect of timing of antihypertensive therapy on glomerular injury: comparison between captopril and diltiazem

Recent studies have suggested that the progression of experimental chronic renal disease may be prevented by early use of antihypertensive drugs. It is unclear, however, whether such therapies may also affect established and progressive renal disease. In the present study we compared the effects of captopril (CEI) and diltiazem (CCB), started either at week 10 or at week 24 on the evolution of adriamycin nephropathy (AN). Rats were studied at weeks 7, 16, 24, 32, and 38 of the disease. None of the treatments influenced the development of nephrotic range proteinuria. The use of CCB from week 10 was even associated with increased proteinuria. The moderate hypertension of ADR rats was reduced to the same degree with both drugs. Inulin clearance (GFR) was significantly reduced in all ADR rats. However, in ADR rats treated with CEI from week 10 and in those treated with CCB from week 24, the GFR was relatively higher. Glomerular injury, evaluated by semiquantitative methods, was not ameliorated by CEI treatment. Earlier CCB treatment (week 10) worsened glomerular lesions, whilst CCB treatment initiated at week 24 reduced significantly the degree of mesangial expansion and focal glomerular sclerosis. We conclude that, in addition to their common antihypertensive action, the specific effect of drug therapy seems to be crucially time dependent.