Homocysteine and hydrogen sulfide in epigenetic, metabolic and microbiota related renovascular hypertension

- H2S attenuates RAS activity in the kidney, and therefore has potential to treat renovascular hypertension.
- In metabolic and epigenetic hypermethylation diseases, H2S deficiency exacerbates hypertension.
- High homocysteine, and low H2S is associated with CKD-mediated renovascular hypertension
- Gut dysbiosis contributes to total plasma H2S pool, and affects overall individual's health.

Over the past several years, hydrogen sulfide (H2S) has been shown to be an important player in a variety of physiological functions, including neuromodulation, vasodilation, oxidant regulation, inflammation, and angiogenesis. H2S is synthesized primarily through metabolic processes from the amino acid cysteine and homocysteine in various organ systems including neuronal, cardiovascular, gastrointestinal, and kidney. Derangement of cysteine and homocysteine metabolism and clearance, particularly in the renal vasculature, leads to H2S biosynthesis deregulation causing or contributing to existing high blood pressure. While a variety of environmental influences, such as diet can have an effect on H2S regulation and function, genetic factors, and more recently epigenetics, also have a vital role in H2S regulation and function, and therefore disease initiation and progression. In addition, new research into the role of gut microbiota in the development of hypertension has highlighted the need to further explore these microorganisms and how they influence the levels of H2S throughout the body and possibly exploiting microbiota for use of hypertension treatment. In this review, we summarize recent advances in the field of hypertension research emphasizing renal contribution and how H2S physiology can be exploited as a possible therapeutic strategy to ameliorate kidney dysfunction as well as to control blood pressure.

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