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 of renal kallikrein reduces glomerular filtration rate (GFR) and renal plasma flow (RPF) in hyperfiltering STZ-induced diabetic rats. To investigate whether these actions of kallikrein and its inhibition are kinin-mediated, we used a B2-kinin receptor antagonist (BKA). In STZ-induced diabetic rats with hyperfiltration, renal kallikrein excretion rate was significantly increased (P < or = 0.01), and kinin excretion rate was increased 57%, as compared with control rats. Left kidney GFR and RPF were measured before and during a 40-min infusion of BKA (0.5 micrograms.kg-1.min-1) or vehicle. Infusion of the kinin receptor antagonist reduced the GFR and RPF significantly. GFR was reduced by 18%, from an average baseline value of 2.07 +/- 0.11 to 1.70 +/- 0.06 ml/min, P < or = 0.001 (means +/- SE). RPF was reduced by 25%, from 6.74 +/- 0.38 to 5.06 +/- 0.17 ml/min, P < or = 0.001. Total renal vascular resistance was significantly increased during BKA infusion, P < or = 0.001. Vehicle infusion for the same period had no significant effect on GFR, RPF, or renal vascular resistance. These findings further support the hypothesis that increased renal production of kinins contributes to the renal vasodilation of diabetes.
Department of Medicine, Medical University of South Carolina, Charleston 29425.
A A
AA
Jaffa
P F
PF
Rust
R K
RK
Mayfield
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D065168:Bradykinin Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D007705:Kinins / Q000502:physiology* / Q000652:urine; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D014655:Vascular Resistance; D014664:Vasodilation
D001786:Blood Glucose; D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D007610:Kallikreins