Enhancement of sodium excretion by substance P during saline loading in the canine puppy.

Abstract

Summary: Saline loading in puppies results in an attenuated natriuresis when compared to the normal response by adult animals to the same degree of volume expansion. To characterize an eventual role for kinins in the diuretic response by puppies to saline loading, two experimental protocols were constructed to evaluate the effect of substance P infusion during baseline hydration and acute saline loading. Low dose (10 ng·kg−1·min−1) infusion of substance P during basal conditions did not affect urine flow, sodium excretion or glomerular filtration rate (GFR). The addition of saline loading to the ongoing low dose infusion of substance P produced an increase in urine flow from 3.73 to 12 μ l·min−1·g−1 kidney weight and resulted in a marked increase in urinary sodium excretion from 110 to 851 μ Eq·min−1·g−1 kidney weight. These increases in urine flow and urinary sodium excretion during low dose substance P infusion were significantly greater than those observed during saline loading alone. No significant effect on GFR was observed during either saline loading alone or low dose substance P during saline loading. In Protocol II, the infusion of low dose substance P during an ongoing saline load enhanced diuresis and natriuresis to a greater extent than those receiving only a saline load without affecting GFR. The high dose infusion of substance P (100 ng·kg−1·min−1) during baseline hydration resulted in a natriuresis and diuresis that persisted during the addition of saline despite a significant fall in GFR. Saline loading alone resulted in increased urinary kallikrein activity and the infusion of substance P (10 ng·kg−1·min−1) increased urinary kallikrein activity even further. A significant positive correlation between urinary sodium excretion and urine kallikrein activity was found (r = 0.91, P < 0.01).