PhD Candidate University of Alberta, Alberta, Canada
An egg white-derived peptide IRW (Ile-Arg-Trp) reduces blood pressure in spontaneously hypertensive rats (SHRs), through modulating renin-angiotensin-system and endothelial dysfunction with mitigated vascular resistance, inflammation and oxidative stress. LRW (Leu-Arg-Trp), a structural analog of IRW derived from pea protein, differs only one amino acid. LRW was reported to possess potent angiotensin converting enzyme (ACE) inhibitory activity in vitro as that of IRW. Our recent study showed that LRW also had a comparative anti-inflammatory activity as that of IRW in vascular endothelial cells. Since in vitro ACE inhibition and vascular anti-inflammation play important roles in regulating high blood pressure, we therefore hypothesized that LRW can reduce blood pressure in SHRs. LRW was orally administrated to the animals over 18 days at a dose of 15 mg/kg body weight per day. However, LRW did not result in blood pressure reduction as it was expected. To explore the underlying mechanism, animal tissues were further analyzed. Results showed that LRW did not attenuate vascular inflammation and oxidative stress, which indicated a different in vivo mechanism of action from that of IRW. Moreover, LRW was more susceptible to gastrointestinal digestion than IRW as well as a possible lower absorption as indicated from a transport study in the human intestinal Caco-2 cell monolayers. The lower gastrointestinal stability and absorption of LRW indicated its lower bioavailability than IRW, which possibly explained its lack of efficacy in blood pressure reduction in SHRs.