Abstract
Urinary kallikrein is a renal enzyme that cleaves kininogen, an α-globulin substrate, to produce kallidin (lysyl-bradykinin), a potent vasodilator kinin (1). In the 40 years since kallikrein was first detected in human urine, a number of workers have shown that kallikrein excretion is altered in patients (2-5) and animals (6-8) with various forms of hypertension. We have shown that urinary kallikrein is subnormal in patients with essential hypertension and supranormal in patients with primary aldosteronism (4, 9, 10). We have also shown that urinary kallikrein is regulated by the activity of sodium-retaining steroids, and thus, by the level of sodium intake (11). The purpose of this study was to determine the effects of chronic renal arterial stenosis on kallikrein excretion in the dog.
Methods. Nine female mongrel dogs weighing 20 to 25 kg were anesthetized with sodium thiamylol and halothane and then the left renal artery was narrowed by suture ligatures according to the method of Lupu and his co-workers (12). The artery was narrowed progressively until a Carolina electromagnetic flow meter showed a greater than 75% reduction in blood flow to the kidney. During the same period of anesthesia bilateral ureterostomies were performed after excision of the bladder, by division of the trigone and suturing of each ureterovesical junction to the lower anterior abdominal wall. At least 10 days later (18.2 ± 5.6, mean ± SEM), when the dogs had fully recovered, they were made to lie on an animal operating table and passively restrained. An infusion of 5% dextrose in water, 15 to 20 ml/min was given into a jugular vein. Urine was collected via small polyethylene catheters placed in each ureter. After urine flow had stabilized, approximately 45 to 90 min after the start of the infusion, urine was collected for 20- or 30-min periods.
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