COMPARISON OF CONVERTING-ENZYME-INHIBITOR AND CALCIUM-CHANNEL BLOCKER IN HYPERTENSIVE GLOMERULAR INJURY

The protective effect of converting enzyme inhibitors in experimental hypertensive glomerular injury is associated with decreased systemic arterial and glomerular capillary pressue. Although calcium channel blockers effectively lower systemic blood pressure, their effect on glomerular capillary pressure and on hypertensive glomerular injury is uncertain. We compared equihypotensive treatment with the calcium antagonist TA 3090 or the converting enzyme inhibitor captopril in post-salt hypertensive Dahl salt-sensitive (DS) rats for up to 5 weeks after five sixths nephrectomy. Before the nephrectomy, all rats demonstrated hypertension (mean 177 mm Hg), proteinuria (mean 175 mg/day), and mild glomerulosclerosis (mean injury score 35). Rats treated with captopril or TA 3090 demonstrated a significant and equivalent decrease in systolic blood pressure compared with untreated rats at 2, 3, and 5 weeks after five sixths nephrectomy; however, only captopril reduced proteinuria. Final proteinuria was actually increased in rats treated with TA 3090 cmpared with untreated rats. Glomerular injury score was significantly decreased in captopril-treated compared with untreated rats at 2 weeks (33 ± 9 versus 117 ± 10, p < 0.05) and 5 weeks (46 ± 9 versus 94 ± 24, p < 0.05), whereas treatment with TA 3090 delayed but did not prevenent progressive glomerular injury (2-week score 35 ± 7, p < 0.05 versus untreated; 5-week score 109 ± 19, p = NS versus untreated). Thus, in hypertensive DS rats after subtotal nephrectomy, treatment with a converting enzyme inhibitor reduced systemic blood pressure, proteinuria, and glomerulosclerosis. However, equihypotensive treatment with a calcium channel blocker did not reduce proteinura and delayed but did not prevent glomerulosclerosis. Thus, in the rat similar reductions in systemic blood pressure with these two classes of agents have disparate effects on the progression of chronic renal failure.