Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria

Abstract

The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA; TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (P(GC)). Treatment with lisinopril lowered the P(GC) to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated P(GC). While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on P(GC); each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone. These data suggest that CA and ACEI have different effects on renal hemodynamics in diabetic dogs and, further, that both glomerular hypertension and glomerular hypertrophy are involved in the proteinuria observed in diabetic dogs.