Scope: It is found in the previous study that egg-white-derived antihypertensive peptide Ile-Arg-Trp (IRW) upregulated angiotensin converting enzyme 2 (ACE2) in spontaneously hypertensive rats (SHRs). The objective of this study is to evaluate the contribution of ACE2 activation by IRW to blood-pressure-lowering activity in vivo. Methods and results: Adult male SHRs (13–15 week old) are assigned into four groups: 1) untreated with saline infusion; 2) IRW administration (15 mg per kg body weight) with saline infusion; 3) Mas receptor (MasR) antagonist A779 (48 µg per kg body weight per h) infusion; 4) A779 infusion and IRW. Animals are implanted with telemetry transmitter first, and then an osmotic pump filled with saline or A779 is implanted. A779/saline is infused for 7 days, continued with an additional 7 days of treatments. Results indicate that blocking MasR abolished the blood-pressure-lowering effect of IRW. Akt/eNOS signaling in aorta is upregulated by IRW treatment but deactivated by A779 infusion. Circulating levels of interleukin 6 and monocyte chemoattractant protein 1, along with cyclooxygenase 2 in aorta are reduced by IRW but restored by A779 infusion. Conclusion: IRW reduces blood pressure of SHR via the ACE2/Ang (1-7)/MasR axis. Mechanisms pertaining to IRW as an ACE2 activator in vivo include enhanced endothelium-dependent vasorelaxation and reduced vascular inflammation.
|Journal||Molecular Nutrition and Food Research|
|State||Published - May 2019|
Bibliographical noteFunding Information:
The authors would like to acknowledge Mrs. Sareh Panahi for providing technical support in doing animal surgery. This research was funded by a grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to J.W. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. S.T.D. is a Canada Research Chair in Maternal and Perinatal Cardiovascular Health. W.L. designed and performed the experiments, and wrote the manuscript; H.F. performed the experiments and analyzed the data; S.T.D. and J.W. designed the experiments.
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- bioactive peptides
- blood pressure
ASJC Scopus subject areas
- Food Science