Gly-Val-Arg, an angiotensin-I-converting enzyme inhibitory tripeptide ameliorates hypertension on spontaneously hypertensive rats

[Display omitted] •Long term administration of the tripeptide GVR to SHRs significantly reduced SBP.•Administration of tripeptide GVR did not cause liver and kidney tissues damage.•Tripeptide GVR demonstrated endothelium-dependent vasorelaxation activity.•LD50 of tripeptide GVR was estimated to be m...

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Bibliographic Details
Published in:Process biochemistry (1991) 2018-06, Vol.69, p.224-232
Main Authors: Manoharan, Sivananthan, Shuib, Adawiyah Suriza, Abdullah, Noorlidah, Ashrafzadeh, Ali, Kabir, Nurul
Format: Article
Language:English
Subjects:
Abnormalities
ACE inhibitors
Acute toxicity
Angiotensin
Antihypertensive activity
Blood pressure
Body weight
Endothelium
Endothelium-dependent vasorelaxation
Hypertension
Kidneys
Liver
Metabolites
Metabolomic
Metabolomics
Oral administration
Pleurotus pulmonarius
Proteins
Proteomic
Proteomics
Rats
Renin
Thorax
Toxicity
Tripeptide GVR
Vasodilation
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Summary:[Display omitted] •Long term administration of the tripeptide GVR to SHRs significantly reduced SBP.•Administration of tripeptide GVR did not cause liver and kidney tissues damage.•Tripeptide GVR demonstrated endothelium-dependent vasorelaxation activity.•LD50 of tripeptide GVR was estimated to be more than 2000 mg/kg body weight.•Metabolomic and proteomic analyses revealed GVR treatment probably influenced renin angiotensin system. The tripeptide GVR was previously shown to inhibit ACE and was able to reduce systolic blood pressure in SHRs within 6 h after administration. To further analyse the potential of tripeptide GVR in lowering blood pressure, a long term study was carried out where the tripeptide was orally administered to SHRs for 21 days. Elevated systolic blood pressure was significantly reduced when the peptide was administered at 50 mg/kg body weight and 100 mg/kg body weight. Body weight of the SHRs did not change significantly between the studied groups and the histopathological findings indicated that there were no abnormalities in liver and kidney tissues. From the acute toxicity analysis of this tripeptide, using the Up and Down method revealed that the peptide was non-toxic to SHRs. Tripeptide GVR demonstrated endothelium-dependent vasorelaxation activity using thoracic aortas from SD rats in which vasorelaxation was not observed in denuded aortas. The metabolomic analysis carried out from the sera of SHRs demonstrated changes on metabolites associated with pathways related to renin angiotensin system. As for proteomic analysis, differentially expressed proteins detected were mainly proteins related with inflammation. Based on the results, tripeptide GVR has a potential to ameliorate the elevated blood pressure in SHRs.
ISSN:1359-5113
1873-3298
DOI:10.1016/j.procbio.2018.03.014