Hemodynamics of the Isolated Perfused Rat Kidney in the Absence and Presence of Kallikrein Substrate

Summary

Rat kidneys were isolated and perfused for 120 minutes at 80mm Hg with Krebs-Henseleit buffer containing 7gm% bovine albumin fraction V. Analysis of the bovine albumin revealed the presence of a contaminating kallikrein substrate which exhibited a MW of 55.000 upon gelfiltration on Sephadex G-200, similar to the reported MW of bovine low molecular weight kininogen. The mean values for renal perfusate flow rate (RPF) and glomerular filtration rate (GFR) in kidneys perfused with this bovine albumin depleted of the kallikrein substrate were significantly lower when compared to standard perfusions. In two other groups of isolated kidneys perfused with kallikrein substrate depleted bovine albumin, purified bovine low molecular weight kininogen (bLMWK, 8.5μg protein in 50μl per minute) or synthetic bradykinin (Bk, 1 ng in l0μ1 per minute) were infused after the first 30 minute clearance period into the renal artery. The induced hemodynamic changes were similar in that RPF and GFR significantly increased. These studies show that depletion of bovine albumin from kallikrein substrate results in a concomitant decrease of RPF and GFR, while overall renal function is unaffected. Infusion of both bLMWK or BK to kallikrein substrate depleted bovine albumin has similar effects resulting in a simultaneous increase in RPF and GFR. This suggests that endogenous kallikrein from the perfused kidney releases kinin from infused bLMWK and indicates that kinin primarily affects the afferent arterioles.