Effects of Intracerebroventricular Infusion of Fab Fragments of Digoxin Antibody(Digibind) on Development of Reduced Renal Mass-Saline Hypertension in Rats.
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To clarify the role of brain ouabain-like compound in reduced renal mass-saline hypertension, we examined the effects of intracerebroventricular infusion of the Fab fragments of antidigoxin antibody (Digibind) on the change in blood pressure of saline-drinking subtotally nephrectomized rats. Twenty male Wistar rats weighing 250g each underwent subtotal nephrectomy. Two groups of 10 rats received Intracerebroventricular infusion of Digibind (20mg/ml) or normal sheep IgG (20mg/ml) at a rate of 0.5 μl/h for 11 days. All rats began to drink 1% NaCl solution after two days of infusion. Systolic blood pressure was measured by the tail-cuff method on days 2, 6 and 9 of infusion. Two groups of saline-drinking rats with reduced renal mass developed hypertension. However, systolic blood pressure was significantly higher in Digibind-infused rats than in IgG-infused rats (day 2, 144±3(SEM) vs. 133± 1mmHg, p<0.05; day 6, 161±4 vs. 151±2mmHg, 0.05<p<0.1, day 9, 181±8 vs. 155±2mmHg, p <0.05). In spite of similar renal dysfunction, plasma aldosterone concentrations, and plasma OLC levels, the accelerated increase in blood pressure was accompanied by a significantly impaired pressure-natriuresis relationship (0.089±0.013 vs. 0.131±0.013mmol/day/mmHg, p<0.05). These results indicate that chronic intracerebroventricular infusion of Digibind augmented reduced renal mass-saline hypertension in rats and suggest that brain ouabain-like compound may play a protective role against the elevation of blood pressure, at least in this model of hypertension. (Hypertens Res 1995; 18: 145-150)
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