The kallikrein-kinin system of the kidney is thought to influence renal hemodynamics, water and electrolyte excretion. The mechanisms which control this system are uncertain. Microperfusion techniques will be used in the rat to study the site, rate and control of kallikrein secretion in the renal tubule. Kallikrein will be measured by a new microkininogenase assay and, if possible, by a direct kallikrein immunoassay of increased sensitivity under development.
Specific aims are as follows. 1. Locate the nephron site or sites at which kallikrein is secreted into the urine and quantify the rate of secretion. 2. Evaluate the effect of changes in urine flow and electrolyte concentrations on the rate of kallikrein secretion. 3. Determine whether the reported effects of changes in renal hemodynamics (renal blood flow, arterial and venous pressure) on kallikrein excretion are direct or secondary to changes in urine flow and composition. 4. Study the effects of hormones (mineralocorticoids, prostaglandins, angiotensin) on tubular secretion of kallikrein. 5. Evaluate the influence of diuretics and vasodilators on tubular kallikrein secretion when urine flow and composition are held constant. 6. Determine whether the kallikrein-kinin system influences distal tubular water and electrolyte transport. In addition, efforts will be made to develop an ultrasensitive kinin assay, in which case similar microperfusion studies of the locus, rate and control of kinin formation in the tubule will become possible. These studies should increase knowledge of a hormonal system which influences kidney function and may play a role in hypertension.
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