Modulation of renal kallikrein production by dietary protein in streptozotocin-induced diabetic rats.
Renal kallikrein levels and excretion rates are increased in insulin-treated diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD) diabetic rats that display renal vasoconstriction show reduced levels and excretion rates of renal kallikrein. In these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin-treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikrein excretion rate were increased compared with SD rats fed the 25% protein 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 versus 120 +/- 30 micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excretion 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 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold decrease 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 activity.
Jaffa
A A
AA
Department of Medicine, Medical University of South Carolina 29425, USA.
Silva
R H
RH
Kim
B
B
Mayfield
R K
RK
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007328:Insulin / Q000627:therapeutic use; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013311:Streptozocin
D000199:Actins; D001786:Blood Glucose; D004044:Dietary Proteins; D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D007610:Kallikreins