Dissecting the potential mechanism of antihypertensive effects of RVPSL on spontaneously hypertensive rats via widely targeted kidney metabolomics.

Abstract

Our previous study has demonstrated that the egg-white-derived peptide RVPSL can lower blood pressure in spontaneously hypertensive rats (SHRs), but its potential action mechanism remains unclear. In this work, the underlying mechanism of the antihypertensive effects of RVPSL in SHRs was elucidated using the widely targeted kidney metabolomics approach. Ten SHRs were divided into two groups: SHR-Untreated group (0.9% saline) and SHR-RVPSL group (50 mg kg-1 body weight RVPSL) for 4 weeks. After 4 weeks, kidney samples were collected and widely targeted (liquid chromatography-electrospray ionization-tandem mass spectrometry) metabolomics was used to detect metabolites. Fifty-six biomarkers were identified that may be associated with hypertension. Among them, 17 biomarkers were upregulated and 39 biomarkers were downregulated. The results suggested that eight potential biomarkers were identified in kidney samples: O-phospho-l-serine, tyramine, citric acid, 3-hydroxybutyrate, O-acetyl-l-serine, 15-oxo-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-oxoETE), dopaquinone and 3,3',5-triiodo-l-thyronine. These potential biomarkers mainly involved carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. The study suggested that RVPSL may exert antihypertensive effects through upregulation of O-phospho-l-serine, 3-hydroxybutyrate and 15-oxoETE, and downregulation of tyramine, citric acid, O-acetyl-l-serine, 3,3',5-triiodo-l-thyronine and dopaquinone. The antihypertensive effects of RVPSL may be related to carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. RVPSL exhibited a potent antihypertensive effect, and the antihypertensive effects were associated with inhibition of vascular smooth muscle cell proliferation, vascular remodeling, vascular endothelium dysfunction, restoring reactive oxygen species, oxidative stress, inflammation and immune reaction. © 2022 Society of Chemical Industry.