ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND CALCIUM-CHANNEL BLOCKADEBOTH NORMALIZE EARLY HYPERFILTRATION IN EXPERIMENTAL DIABETES, BUT ONLY THE FORMER PREVENTS LATE RENAL STRUCTURAL DAMAGE

We studied the potential renoprotective properties of a calcium channe l blocker in moderately hyperglycemic diabetic rats both in the early phase of the disease and in the very long term, and compared such an e ffect with that of an angiotensin-I-converting enzyme (ACE) inhibitor. Three groups of diabetic rats, one receiving no therapy except insuli n and the remaining two receiving insulin and the ACE inhibitor enalap ril or the calcium blocker lacidipine and one group of nondiabetic con trol rats were followed for 4-6 weeks. Both antihypertensive drugs low ered systolic blood pressure comparably. At the end of the observation period, untreated diabetic rats exhibited elevation of glomerular fil tration rate and renal plasma flow. Both enalapril and lacidipine trea tment completely prevented whole-kidney hyperfiltration and hyperperfu sion. Four additional groups of rats, similarly treated, were followed for 1 year. A comparable control of systolic blood pressure and blood glucose level was achieved with the two antihypertensive regimens thr oughout the whole study period. At 12 months, the average kidney weigh t was elevated to similar values in all. diabetic groups relative to c ontrol rats. Untreated diabetic rats had progressive proteinuria and d eveloped glomerulosclerosis. Enalapril markedly limited the developmen t of proteinuria. By contrast, urinary protein excretion in diabetic r ats given lacidipine markedly increased with time, and values were as high as those in untreated diabetic animals. Similarly, only enalapril was effective in limiting glomerular injury. These results indicate t hat ACE inhibition but not calcium channel blockade has a favorable ef fect in preventing renal disease progression in diabetic rats and sugg est that the various antihypertensive regimens are not equally benefic ial in protecting against diabetic glomerulopathy.