Understanding Hypertension as a Metabolic Disease Through the Relationship Between Metabolites and Hypertension

Essential hypertension has been studied from a variety of angles for more than a century, including genetics, physiology, immunology, and more recently, microbiology (microbiota), an unnoticed field of study that contributes to the aetiology of hypertension. In isolation, each area of research has made a distinct contribution to a range of fundamental blood pressure regulating processes. Nevertheless, there has been little change in the clinical care of essential hypertension. The researchers of the current review offered a growing body of evidence that supports the idea that essential hypertension is caused by metabolic dysfunction.

The Dahl Salt-Sensitive (S) and Salt-Resistant (R) models in experimental models were used to assess the genetic causes of hypertension, with S experimental models developed hypertension and insulin resistance on high-salt diets, unlike R experimental models. This metabolic dysfunction appeared before hypertension, indicating overlapping pathways for blood pressure regulation and metabolism. The SS/MCW strain shows lower fumarase activity, leading to the accumulation of tri-carboxylic acid (TCA) cycle metabolites that contribute to hypertension. Additionally, mutations in the Cyp11b1 gene could affect adrenal steroid metabolism in S experimental models, associating them to hypertension. The Spontaneously Hypertensive Rat (SHR) also exhibited metabolic defects, and genetic research has identified Cd36 as a critical locus for insulin resistance and hypertension.

Similar trends were observed in humans, where genome-wide association studies (GWAS) have identified links between hypertension and lipid metabolism. Thus, metabolic dysfunction is closely connected to hypertension, suggesting that controlling metabolic health may be essential to successfully lowering blood pressure. Future research could provide more insight into how microbial and host metabolites affect hypertension and the liver's function in this process.

Source:Chakraborty S, Mandal J, Yang T, Cheng X, Yeo JY, McCarthy CG, Wenceslau CF, Koch LG, Hill JW, Vijay-Kumar M, Joe B. Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder: 2019 Harriet Dustan Award. Hypertension. 2020 Jun;75(6):1386-1396. doi: 10.1161/HYPERTENSIONAHA.120.13896. Epub 2020 Apr 27. PMID: 32336227; PMCID: PMC7225070.