Short and long term effects of antihypertensive therapy in the diabetic rat

To compare the impact of differing antihypertensive regimens on the development of renal injury, studies were performed in three groups of moderately hyperglycemic diabetic rats, and one group of non-diabetic control (C) rats. One diabetic group (DM) received no therapy except insulin. The remaining diabetic group received insulin and either the angiotensin I converting enzyme inhibitor captopril (CAP), or triple therapy (TRX) with reserpine, hydralazine and hydrochlorothiazide. CAP and TRX modestly and comparably lowered blood pressure. At 6 to 10 weeks, DM rats exhibited elevation of the single nephron glomerular filtration rate (SNGFR), due to elevations of the glomerular capillary plasma flow rate (Q(A)) and the glomerular capillary hydraulic pressure (P̄(GC)). In both DM/CAP and DM/TRX rats, blood pressure reduction was associated with selective normalization of P̄(GC), without change in SNGFR or Q(A). In long-term (70 weeks) studies, DM rats exhibited progressive albuminuria and marked glomerular sclerosis. CAP limited albuminuria and injury to values even lower than those in C rats, whereas TRX served only to delay, but not to prevent, the increase in albuminuria. TRX reduced glomerular sclerosis, but was less effective than CAP. At 70 weeks, CAP and TRX still reduced systemic blood pressure; P̄(GC) remained at normal levels with CAP but was no longer controlled with TRX. These results confirm the clinical observation that antihypertensive therapy slows diabetic glomerulopathy, but also suggest that CAP affords superior long-term protection as compared to the other antihypertensive drug regimen studied.