32-amino acid B-type natriuretic peptide (BNP 1-32) plays an important role in cardiovascular homeostasis. Recently, it was reported that BNP 1-32 is cleaved by the metalloprotease meprin A to BNP 8-32, the bioactivity of which is undefined. We hypothesized that BNP 8-32 has reduced vasodilating and natriuretic bioactivity as compared to BNP 1-32 in vivo. Human BNP 8-32 and BNP 1-32 were compared in a crossover study in eight anesthetized normal canines. After a preinfusion clearance, BNP 1-32 was infused at 30 ng/kg/min for 45 minutes followed by a 60' washout and a second preinfusion clearance. Then, equimolar BNP 8-32 was infused. In half the studies the peptide sequence was reversed. Changes with peptides from the respective preinfusion clearance to infusion clearance were compared with paired tests. Mean arterial pressure was reduced by both BNP 8-32 and BNP 1-32 (-8±3 vs -6±2 mmHg, p=0.48). Changes in right atrial pressure, pulmonary capillary wedge pressure, heart rate, cardiac output, and glomerular filtration rate were similar. However, urinary sodium excretion increased less with BNP 8-32 than with BNP 1-32 (+171±24 vs +433±43 µEq/min; p=0.008), as did urinary potassium excretion, urine flow, and renal blood flow. While BNP 8-32 has similar vasodilating actions as BNP 1-32, its diuretic and natriuretic actions are reduced, suggesting an important role for meprin A in the regulation of BNP 1-32 bioactivity in the kidney. Meprin A inhibition may be a potential strategy to increase the bioactivity of endogenous and exogenous BNP 1-32 in cardiovascular diseases.