Figure 1: Connecting metabolism to blood supply.
He et al.3 have found that the ‘orphan’ G-protein-coupled receptors GPR91 and GPR99 detect succinate and α-ketoglutarate — intermediates produced by the tricarboxylic acid (TCA) cycle during respiration. They also find that succinate increases blood pressure in mice. The figure shows how this happens. A local mismatch of energy supply and demand, altered metabolism of TCA-cycle intermediates, or injury leads to mitochondrial dysfunction and the release of succinate and α-ketoglutarate. These molecules activate receptors in the kidney, causing the release of renin and activation of the renin–angiotensin system (RAS). The RAS leads to an increase in blood pressure and altered local blood flow. Physiologically, this system might act to regulate local blood flow to match metabolic demands. However, it might also result in hypertension or alter cellular function.
