High-altitude hypoxic environments significantly affect the cardiovascular system and blood pressure regulation. However, the underlying pathological mechanisms remain unclear, necessitating further studies on the effect of high-altitude hypoxic exposure on blood pressure. We established a long-term high-altitude hypoxia exposure model, exposing spontaneously hypertensive rats (SHRs) to high-altitude hypoxia for 10 weeks, and performed quantitative proteomics and metabolomics of the abdominal aorta of SHRs using tandem mass tag-based quantitative proteomics and metabolomics. Analysis using bioinformatics and enrichment strategies indicated that the altered proteins and metabolites participate in various biological processes. The differentially expressed proteins primarily participate in oxidative phosphorylation pathways, thermogenesis, the tricarboxylic acid cycle, and carbon metabolism. We speculated that oxidative phosphorylation and thermogenesis were related to the reduced blood pressure in SHRs under high-altitude hypoxic conditions. Combined proteome and metabolome analyses revealed that altered metabolites, including thiamine, S-adenosylhomocysteine, pantothenic acid, fumaric acid, and homoserine, participated alongside differentially expressed proteins in the process of blood pressure reduction in high-altitude hypoxic environments in SHRs. This study elucidated the potential molecular mechanisms underlying blood pressure reduction in SHRs under high-altitude hypoxic conditions by integrating proteomics and metabolomics, providing insights into exploring how high-altitude hypoxia affects blood pressure at the molecular level.

High-altitude hypoxia affects respiratory, central nervous, cardiovascular, and endocrine systems. These outcomes affect the expression of cytochrome P450 (CYP), the most important family of metabolic enzymes in the body involved in the metabolism of both exogenous and endogenous substances. Hypoxia influences CYP expression and activity, mediating changes in drug and endogenous substance metabolism, with endogenous substance metabolites playing a substantial role in controlling high-altitude diseases. However, the mechanisms that regulate CYP changes under hypoxic conditions and the effects of CYP changes on drug and endogenous metabolism remain unclear. We examined how CYP expression and function change during hypoxia and how they are controlled by nuclear receptors, epigenetic modifications, cytokines, and gut microbiota during hypoxia. This was done to understand how CYP affects the metabolism of drugs and endogenous substances, such as arachidonic acid, vitamins, and steroid hormones during hypoxia, and to determine how CYP and its metabolites are involved in the pathophysiology of diseases linked to high-altitude hypoxia.