MODULATION OF RENAL KALLIKREIN PRODUCTION BY DIETARY-PROTEIN IN STREPTOZOTOCIN-INDUCED DIABETIC

Renal kallikrein levels and excretion rates are increased in insulin-t reated diabetic rats with hyperfiltration, and inhibition of kallikrei n or blockade of kinin receptors reduces GFR and RPF, In contrast, ins ulin-deprived severely (SD) diabetic rats that display renal vasoconst riction show reduced levels and excretion rates of renal kallikrein. I n these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodyna mic regulation. Insulin-deprived SD and insulin-treated moderately dia betic (MD) rats were fed a low (9%), normal (25%), and a high (50%) pr otein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikr ein excretion rate were increased compared with SD rats fed the 25% pr otein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 ml/min; RPF, 7.78 +/- 0.58 versus 5.14 +/- 1.03 ml/min; total kallikrein, 248 +/- 24 ver sus 120 +/- 30 mu g/24 h, SD 50% versus SD 25%, respectively; P < 0.00 5). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excre tion rate were significantly reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/- 0.09 ml/min; RPF, 5.58 +/- 0. 35 versus 7.81 +/- 0.35 ml/min; total kallikrein, 119 +/- 8.3 versus 2 19 +/- 15 mu g/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Pr otein restriction in normal nondiabetic rats resulted in a twofold dec rease in kallikrein mRNA levels. These findings suggest that the renal hemodynamic response to dietary protein manipulation in diabetic rats could be mediated via changes in renal kallikrein-kinin system activi ty.