Janos Peti-Peterdi: Succinate and GPR91 Play Role in Renovascular Hypertension

In 2012, Dr. Janos Peti-Peterdi continued to explore urinary succinate and the metabolic receptor GPR91 in a UKRO-funded project. The broad, long-term objective of his work is to establish the importance of succinate/GPR91 signaling and the role of the distal nephron in the pathomechanism of kidney disease and renovascular hypertension (RVHT). He theorizes that, in response to reduced blood (oxygen) supply to the kidney, succinate accumulation and GPR91 signaling locally activate the renin-angiotensin system; this signaling mediates, at least in part, the complex signaling pathways that result in the development of hypertension and related pathologies, including tissue fibrosis. He is currently working to determine the importance of GPR91 signaling in the development of RVHT. Another sub-aim of the study is to develop urinary succinate as a novel biomarker and predictor of hypertension.

His latest studies have shown that GPR91/succinate signaling is a major player in the control of intra-renal renin (RAS) and blood pressure in renovascular hypertension. The data he has obtained so far are consistent with the important role of succinate/GPR91 signaling in the development of RVHT.  The blood pressure data, in particular, are exciting and suggest that GPR91 may be developed as a new drug target in hypertension and kidney disease.

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