Effects of antihypertensive drugs in experimental type 2 diabetes-related nephropathy

Abstract

It has been extensively reported that antihypertensive drugs reduce proteinuria and glomerulosclerosis (GS) in many experimental nephropathies and in humans. However, the role of calcium channel blockers (CCBs) in the prevention of proteinuria and GS remains controversial and in most cases only dihidropyridine-CCBs are studied. Few studies have reported whether the time at which drug administration is initiated plays a role in the reduction of proteinuria and GS. Fifty-six male Obese Zucker rats (OZR) were used as a model of spontaneous type 2 diabetes-related nephropathy. Biochemical and histological analysis were performed to compare the efficacy of a non-dihydropyridine-CCB diltiazem [DZM; 100 mg/kg body weight (BW)/day], an ACEI quinapril (10 mg/kg BW/day), or both in diminishing proteinuria and GS, and to determine their role in effective prevention and treatment. Only quinapril was able to diminish proteinuria. As far as histological lesions, both treatments were effective, although only quinapril prevented GS. The combination of quinapril plus DZM did not demonstrate any beneficial effects. Surprisingly, quinapril ameliorated the damage of podocytes whereas DZM did not, thus leading to doubt concerning the efficiency of DZM in long-term studies. Nonetheless, the combination of quinapril plus DZM demonstrated a greater reduction in podocyte damage than treatment with DZM alone, which shows an interesting association in the prevention of longer-term glomerular damage. Few differences were found between prevention and treatment. Quinapril, but not DZM, was able to diminish proteinuria in OZR. Both treatments were effective in diminishing GS, although only quinapril totally prevented it. The combination of both drugs prevented long-term glomerular damage, which is intriguing.