Changes in the enzymes involved in Ang II degradation may influence disease conditions such as hypertension and kidney disease. The enzyme prolylcarboxypeptidase (PRCP) catalyzes the conversion of Ang II to Ang(1-7) and its deficiency results in a phenotype characterized by a prothrombotic state, hypertension, and impaired wound healing. Here, we investigated kidney function and blood pressure in young mice, 10-16 weeks of age, with a subtotal PRCP deficiency (PRCP genetrap, PRCPgt).
Enzyme activity based on a synthetic fluorogenic peptide was used to measure PRCP activity. The activity of recombinant PRCP was strongly pH-dependent with an optimum in the acidic range (pH 5). In keeping with this, recombinant PRCP degraded Ang II at pH 5, but not at pH 7.4 in-vitro. PRCP activity was detected in serum and in kidney of WT mice whereas PRCPgt/gt mice displayed highly diminished serum PRCP activity (about 5% of the WT).
Kidney function was assessed by urinary protein/creatinine ratio and GFR. At 10 weeks of age, neither female nor male PRCPgt/gt animals showed elevations in urinary protein/creatinine-ratio (female PRCPgt/gt 19.9±1.4 vs. WT 23.5±1.9 and male PRCPgt/gt 32.4±3.5 vs. WT 34.8±1.8). At 16 weeks of age, the GFR (measured by clearance of FITC-Inulin) was not different (female PRCPgt/gt 4.10±0.32 vs. WT 4.33±0.29 and male PRCPgt/gt 4.41±0.50 vs. WT 4.28±0.31 ul/min/g). Systolic blood pressure was significantly elevated in PRCPgt/gt animals as compared to the respective WT controls (female PRCPgt/gt 147.8±3.4 vs. WT 117.3±7.1 mmHg, male 138.1±8.4 vs. 120.5±3.6 mmHg, p<0.05).
PRCP deficient mice have normal GFR but elevated basal blood pressure. Whether PRCP deficiency causes hypertension as a result of impaired Ang II degradation or other mechanisms needs to be determined.