Effects of alterations in sodium and water metabolism on urinary excretion of active and inactive kallikrein in man.
Renal kallikrein is present in human urine in both an active and an inactive form. Several previous studies have examined the response of active kallikrein excretion to alterations in sodium and water metabolism, but the response of inactive kallikrein has not been evaluated systematically. We have developed a method for determining inactive kallikrein in urine using two assays. Active kallikrein is measured using a kininogenase assay. Total (active plus inactive) kallikrein is measured using a direct RIA. Inactive kallikrein is calculated from the difference between active and total kallikrein excretion. We have used this technique to study the effect of alterations in sodium and water metabolism on kallikrein excretion. Acute volume expansion with saline and moderate acute or chronic increases in water intake did not alter the excretion of either active or inactive kallikrein. Dietary sodium restriction increased the excretion of total kallikrein by 30%; active kallikrein increased 82%, while inactive kallikrein excretion was found to be unchanged. Spironolactone reduced total kallikrein excretion in subjects on a low salt diet. Again, the change in excretion was entirely attributable to the active form of the enzyme. Total kallikrein excretion increased during the first 3 days of fludrocortisone administration in subjects on a high salt intake and then plateaued. Active kallikrein increased progressively throughout the 7-day study period. Inactive kallikrein increased during the first 4 days, then fell to control levels. Thus, mineralocorticoid initially stimulates the formation and/or release into urine of both active and inactive kallikrein. Later, reciprocal changes in active and inactive enzymes occur.
D001834:Body Water / Q000378:metabolism*; D004039:Diet, Sodium-Restricted; D005260:Female; D005438:Fludrocortisone / Q000494:pharmacology; D006801:Humans; D007610:Kallikreins / Q000652:urine*; D008297:Male; D011863:Radioimmunoassay; D012964:Sodium / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D014867:Water / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D014867:Water; D013148:Spironolactone; D012964:Sodium; D007610:Kallikreins; D005438:Fludrocortisone