Common Metabolites in Two Different Hypertensive Mouse Models: A Serum and Urine Metabolome Study

Abstract

Recent metabolomics studies have identified a wide array of microbial metabolites and metabolite pathways that are significantly altered in hypertension. However, whether these metabolites play an active role in pathogenesis of hypertension or are altered because of this has yet to be determined. In the current study, we hypothesized that metabolite changes common between hypertension models may unify hypertension’s pathophysiology with respect to metabolites. We utilized two common mouse models of experimental hypertension: L-arginine methyl ester hydrochloride (L-NAME)/high-salt-diet-induced hypertension (LSHTN) and angiotensin II induced hypertension (AHTN). To identify common metabolites that were altered across both models, we performed untargeted global metabolomics analysis in serum and urine and the resulting data were analyzed using MetaboAnalyst software and compared to control mice. A total of 41 serum metabolites were identified as being significantly altered in any hypertensive model compared to the controls. Of these compounds, 14 were commonly changed in both hypertensive groups, with 4 significantly increased and 10 significantly decreased. In the urine, six metabolites were significantly altered in any hypertensive group with respect to the control; however, none of them were common between the hypertensive groups. These findings demonstrate that a modest, but potentially important, number of serum metabolites are commonly altered between experimental hypertension models. Further studies of the newly identified metabolites from this untargeted metabolomics analysis may lead to a greater understanding of the association between gut dysbiosis and hypertension.

Examination of Serum Metabolome Altered by Dietary Carbohydrate, Milk Protein, and Soy Protein Interventions Identified Novel Metabolites Associated with Blood Pressure: The ProBP Trial

“…[27,28] Similarly, many saturated fatty acids are elevated among hypertensive individuals, and high saturated fatty acids diet increased BP. [29,30] Hydroxy fatty acids have antifungal, anti-inflammation, and anti-diabetes functions and are produced in the process of food fermentation. [31] There are few studies investigating their role in BP regulation.…”

Indole Propionic Acid Increases T Regulatory Cells and Decreases T Helper 17 Cells and Blood Pressure in Mice with Salt-Sensitive Hypertension

“…In addition to maintaining our health on a daily basis, the microbiome can also play a role in disease progression through the production of deleterious metabolites. Recent studies have reported a strong association between dysbiosis in microbiota and hypertension pathology and progression [6][7][8]. Advancements in metabolomic approaches have identified several classes of metabolites that are associated with hypertension, namely short chain fatty acids and trimethylamine-N-oxide [9][10][11][12][13][14][15][16].…”