KININ, A MEDIATOR OF DIABETES-INDUCED GLOMERULAR HYPERFILTRATION

Renal kallikrein is increased in diabetic patients and streptozotocin (STZ)-induced diabetic rats with hyperfiltration. Chronic inhibition o f renal kallikrein reduces glomerular filtration rate (GFR) and renal plasma flow (RPF) in hyperfiltering Sn-induced diabetic rats, To inves tigate whether these actions of kallikrein and its inhibition are kini n-mediated, we used a B-2-kinin receptor antagonist (BKA). In STZ-indu ced diabetic rats with hyperfiltration, renal kallikrein excretion rat e was significantly increased (P less than or equal to 0.01), and kini n excretion rate was increased 57%, as compared with control rats. Lef t kidney GFR and RPF were measured before and during a 40-min infusion of BKA (0.5 mu g kg(-1).min(-1)) or vehicle. Infusion of the kinin re ceptor antagonist reduced the GFR and RPF significantly. GFR was reduc ed by 18%, hom an average baseline value of 2.07 +/- 0.11 to 1.70 +/- 0.06 ml/min, P less than or equal to 0.001 (means +/- SE). RPF was red uced by 25%, hom 6.74 +/- 0.38 to 5.06 +/- 0.17 ml/min, P less than or equal to 0.001. Total renal vascular resistance was significantly inc reased during BKA infusion, P less than or equal to 0.001. Vehicle inf usion for the same period had no significant effect on GFR, RPF, or re nal vascular resistance. These findings further support the hypothesis that increased renal production of kinins contributes to the renal va sodilation of diabetes.