Abstract 455: Decreased Experimental Hypertension and Inflammation in the Absence of Prolylendopeptidase Activity
Objective: Previously, we showed that inhibition of prolyloligopeptidase eliminated the differences in macrophage TNFα expression and BP response in mice lacking N-domain activity of ACE. Thus, functional studies of BP and inflammatory response in a model lacking prolylendopeptidase activity are performed.
Results: After a 14 day high-dose AngII infusion (980 ng/kg-min), POP-KO(n=12) BP was 130±3 mmHg and 147±4 mmHg for POP-WT(n=12). After 14 days of low-dose AngII infusion(490 ng/kg-min), POP-KO(n=8) BP was 126±4 mmHg and 139±3 mmHg for POP-WT(n=8). To investigate differences in the inflammatory response, we examined peritoneal macrophage cytokine expression in response to AngII. The percentage of F4/80+/TNFαhigh cells vs. total F4/80+ was 17%±4.7% for POP-KO (n=8) and 49%±2.8% for POP-WT (n=8)[p<0.005]. The percentage of F4/80+/IL-6high cells vs. total F4/80+ was 15%±3.2% for POP-KO(n=8) and 39%±4.8% for POP-WT(n=8)[p<0.01]. To investigate whether there were baseline differences, TNFalpha secretion was measured in POP-KO(8%) vs. POP-WT(16%) without AngII stimulation. Baseline bone marrow analysis by flow shows 48% CD11b+Ly6ghi cells in POP-KO (n=6) vs. 39% in POP-WT (n=4). Moreover, F4/80hiLy6cintermediate cells were 1.19% in the POP-KO (n=6) vs. 1.75% in POP-WT(n=4).
Conclusion: Inflammation is an emerging player in hypertension and prolylendopeptidase inhibition may play a role in reducing that inflammation. In the POP-KO mouse model, baseline differences in quantity and quality of inflammatory cells may contribute to the phenotypic differences found in vivo.
- © 2012 by American Heart Association, Inc.