Influence of sodium balance on urinary excretion of immunoreactive kinins in rats

Abstract

Antibodies against bradykinin (BK) and its metabolites, namely des-Arg9-BK and des-Phe8,Arg9-BK were raised in rabbits, and specific radioimmunoassays (RIA) for these peptides were developed. Specificity studies showed that each RIA was specific for its antigen, since the cross-reactivities of various kinin-related peptides were less than 1.5%. The lowest concentration of peptide that could be measured in these assays was approximately 60 pg/ml. The antibodies were used to measure concentrations of BK and its metabolites in urine and kidneys of rats maintained on different sodium balance for 5 wk. The results showed that normal rats excrete low quantities of BK (63.78 +/- 2.98 ng/day, 88 determinations). The urinary excretion of des-Arg9-BK averaged 77.69 +/- 5.53 ng/day, whereas the amount of des-Phe8,Arg9-BK is equal to 7.13 +/- 0.42 ng/day. Sodium loading brings about a small decrease in the concentration of BK (45.57 +/- 2.36 ng/day, 76 determinations), whereas sodium depletion significantly increased the excretion of BK (94.23 +/- 5.50, 102 determinations, P less than 0.01) accompanied by no modification of the excretion of metabolites. Regression analysis of the results showed a positive correlation between urinary volume and BK in control and sodium-loaded animals and urinary BK and sodium in the sodium-loaded group. In kidney homogenates, sodium depletion increased not only the concentration of BK (10-fold) but also that of des-Arg9-BK and des-Phe8,Arg9-BK by a factor of four and two, respectively, when compared with normal and sodium-loaded animals. These results support the hypothesis that the renal kallikrein-kinin system may be regulated by corticosteroids.