New insights into the metabolomic signatures of spontaneously hypertensive rats

Abstract

BACKGROUNDHypertension is a major risk factor associated with cardiovascular diseases and one of the leading causes of premature death. Hypertension has no obvious clinical signs; therefore, the identification of new biomarkers for the early detection of people at risk is needed to prevent hypertension and its further complications. Metabolomics is a useful tool for studying in vivo metabolic profiles that better understand the pathogenesis of diseases such as hypertension. This work aimed to explore the plasma and urinary non-targeted metabolic profile of 16-week-old spontaneously hypertensive rats (SHR) to identify new metabolomic profiles associated with hypertensive phenotypical characteristics that allow early diagnosis of patients at risk. METHODSPlasma and 24-hours urine samples were collected from 10 SHR and 10 age-matched normotensive Wistar-Kyoto 16-week-old male rats. Plasma and urinary metabolic profiles were investigated using high-performance liquid chromatography quadrupole time of flight coupled to mass spectroscopy followed by multivariate statistical analysis. The mummichog pathway enrichment analysis was used to integrate metabolomics data into biological contexts. RESULTSA total of 16 differential metabolites were found in plasma and 13 differential metabolites in urine from SHR compared to normotensive rats. Differences in some microbiota-derived metabolites suggest changes in the gut microbiota associated with hypertension in our experimental model. The mummichog algorithm has recognized that hypertensive metabolism is associated with the altered metabolism of steroid hormones, bile acid and purines. CONCLUSIONSThis work highlights the importance of metabolomics as a tool for the identification of biomarkers in the early detection of hypertension, a condition that represents a significant risk to cardiovascular health. The findings suggest that hypertension is associated with alterations in the metabolism of steroid hormones, bile acids and purines, as well as metabolites derived from the intestinal microbiota. These results not only contribute to a better understanding of the pathogenesis of hypertension but also open the door to future research in humans that could facilitate more accurate and earlier diagnoses, thus helping to prevent serious complications associated with this disease.